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Nutritional implications of vertical HIV-1 transmission via breastfeeding in developing countries

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Nutritional implications of vertical HIV-1 transmission via breastfeeding in developing countries
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Williams, Ellana
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Metropolitan State University of Denver
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Nutritional Implications of Vertical HIV-1 Transmission via Breastfeeding
in Developing Countries
by Ellana Williams
An undergraduate thesis submitted in partial completion of the Metropolitan State University of Denver Honors Program
May 5, 2017
Dr. Bruce Rengers Primary Advisor
Dr. Melissa Masters Second Reader
Dr. Megan Hughes-Zarzo Honors Program Director


Nutritional Implications of Vertical HIV-1 Transmission via Breastfeeding in Developing
Countries
Metropolitan State University of Denver Ellana Williams
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
BREASTFEEDING IN DEVELOPING COUNTRIES
Table of Contents
Abstract..................................................................... 3
Acknowledgements............................................................. 4
Introduction................................................................. 5
Issues in Developing Countries
I. Benefits of Breastfeeding..............................................10
II. Breastfeeding with HIV/AIDS............................................15
III. Alternative Methods of Infant Feeding.................................18
IV. Stigma Association.....................................................33
V. Factors Which May Effect Vertical HIV-1 Transmission...................39
Global Health Policy
I. Developing Nations.....................................................47
II. Compliance with Global Health Policy...................................56
Conclusion...................................................................64
References...................................................................69
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
Abstract
The HIV/AIDS epidemic has been a leading cause of death in developing nations; current disease infectivity remains a multifaceted issue throughout endemic areas of the world. Women who are HIV-positive have many risks and barriers in the context of overall nutrition status, coupled with social and economic issues which pose difficulty in determining whether or not to breastfeed. The purpose of this thesis is to provide a literary analysis regarding vertical HIV-1 transmission via breastfeeding in developing countries focusing on nutritional implications and global health policy. Per nutrition research and data, exclusive breastfeeding provides nutritional, immune, and long-term benefits for the infant in conjunction with a variety of maternal benefits. While it has been demonstrated that breastfeeding is the gold-standard method of infant feeding, this choice will therefore pose a controversial and difficult decision for HIV-positive mothers regarding risk of mother-to-child HIV-1 transmission. With culturally appropriate understanding of these complex issues, determination of whether or not women who are HIV-positive should breastfeed will be discussed in correlation with dissimilar global health policy in developed vs. developing nations.
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
Acknowledgements
I would like to thank my primary thesis advisor, Dr. Bruce Rengers of the Human Nutrition and Dietetics Department at Metropolitan State University of Denver for continuous support and direction throughout this endeavor. Without Dr. Rengers participation and input, my Honors thesis would not have been successfully completed. The culmination of this research has invaluably broadened my education in dietetics and inspired me to work with the HIV-positive maternal-infant dyad in the near future.
I would also like to thank Dr. Meghan Hughes-Zarzo, Honors Director at Metropolitan State University of Denver for providing a platform to enhance my education from this challenging, and rewarding accomplishment. Her kind, helpful support and encouragement throughout, has been much appreciated.
I would also like to acknowledge Dr. Melissa Masters of the Human Nutrition and Dietetics Department at Metropolitan State University of Denver as the second reader of my Honors thesis. Thank you for your invaluable discussion, ideas, and feedback.
Finally, I must express my profound gratitude to my family, peers, and Metropolitan State University of Denvers faculty for providing me unfailing support and continuous encouragement throughout this process of researching and writing. This accomplishment would not have been possible without them. Thank you.
Ellana Williams
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
Introduction
Exclusive breastfeeding has been demonstrated as the gold standard method of infant feeding. Infants who are exclusively breastfed are provided with complete nutrition for the first six months of life and additional benefits beyond the six month mark. Breastmilk provides the perfect ratio of macronutrients, with high bioavailability of micronutrients for the infant. As the child grows, breastmilks nutritional composition changes for the infants respective nutritional needs. Infants gain non-nutritive properties from breastmilk as well, including maternal immune factors which function in the infants gastrointestinal tract to actively protect from disease. Breastfed infants have higher IQs and are less likely to acquire illnesses, and other health conditions later in life as often as non-breastfed babies. In developing countries, the benefits of breastfeeding stretch further. According to the World Health Organization (WHO), improving breastfeeding practices, specifically in developing countries, could prevent more than 1 million infant deaths annually.1
Each year, 8.2 million children under the age of five die, with 99% of deaths occurring in developing countries, particularly in Africa and South East Asia.2 Nearly 3.3 million child deaths under the age of five are among neonates infants in their first 28 days of life, while the additional 4.9 child deaths occur between the age of 28 days and five years old.2 The two leading causes of global infant death are respiratory infections, and diarrhea.2 Breastfeeding drastically reduces the incidence of both. In developing countries, breastfeeding is a matter of life and death. Children who are not breastfed are approximately 56% more likely to have prevalent diarrheal episodes, increasing risk of death from dehydration.3 Breastfed infants are also 47% times less likely to die of a respiratory infection such as pneumonia, which is a leading cause of child
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morbidity and mortality.4'5 In order to reduce the prevalence of infant death, breastfeeding is essential to sustain the lives of children, particularly in developing countries.
With the highest rate of infant death localized in Africa and South East Asia, breastfeeding should be a mothers number one priority aimed at reducing infant and child death. Certain extenuating circumstances and contraindications may come to light that influence a womans decision to breastfeed, like the HIV/AIDS epidemic.
HIV-positive mothers can transmit this disease to their children through vertical (mother-to-child) HIV-1 transmission. According to The United Nations Childrens Fund (UNICEF), between 15% and 25% of children born to HIV-infected mothers become vertically infected with HIV in utero, at delivery or during breastfeeding.8 Interventions to reduce mother-to-child HIV-1 transmission to less than 2% include antiretroviral therapy, elective cesarean section (C-section) at delivery, and safe alternative methods of infant feeding. In the absence of any interventions, mother-to-child HIV-1 breastfeeding transmission rates range from approximately 15%-45%.8'9 Roughly 17 million HIV-positive mothers, the majority of which living in Africa and South East Asia, face the challenging decision of whether or not breastfeeding is the best option for themselves and their child.
HIV/AIDS is a leading cause of death in endemic areas of developing nations; disease infectivity remains a multifaceted issue. According to the WHO, in 2015 approximately 36.7 million people were living with HIV, with 2.1 million people becoming newly infected two-thirds of which in Sub-Saharan Africa. This region is the most affected globally with 25.5 million people living with HIV.6 Of the 36.7 million people living with HIV in 2015, only 18.2 million people were receiving antiretroviral therapy drugs worldwide by mid-2016, which is roughly 50% of the infected population.6
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In HIV endemic populations there continues to be major public health issues regarding women who are HIV-positive. HIV-positive women have many risks and barriers in the context of overall nutrition status, coupled with social and economic issues which pose difficulty in determining whether or not to breastfeed. Mothers do not want to pass onto their children a painful, terminal and chronic disease of which life expectancy is shortened. Although, if alternative methods of infant feeding are used, the risk of infant morbidity and mortality consequently increases from a combination of malnutrition, vitamin deficiencies, and additional infectious disease.
In 2015, approximately 17.8 million women were infected with HIV globally, and 150,000 children became newly infected during the course of the year.7 Death follows in the footsteps of an HIV diagnosis, particularly in developing countries. According to a 2015 global factsheet provided by The Joint United Nations Programme on HIV/AIDS (UNAIDS), there were 1.2 million deaths due to AIDS which included 110,000 deaths of children aged 0-14.7 In 2015, there were 13.4 million orphans aged 0-17 as a result of caregivers dying from the disease.7 These numbers are substantial, and can in theory be reduced.
In 2001, 800,000 children under the age of 15 contracted HIV and over 90% of them (720,000 children) from mother-to-child HIV-1 transmission.8 The above statistic is dated and many efforts have been made to reduce vertical HIV-1 transmission rates at the global and public health level. Even with efforts aimed at reducing mother-to-child HIV-1 transmission,
HIV/AIDS is still a prominent issue affecting millions of people annually, therefore risk of transmission is still prevalent especially in developing countries.
Various other issues further complicate the decision for an HIV-positive mother to breastfeed her infant. Numerous nutritional interactions, concerning micronutrient intake,
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macronutrient intake, and overall maternal nutrition status can increase or decrease the risk of mother-to-child HIV-1 transmission via breastfeeding. Social restraints also play a role including social stigmatization of HIV-positive women, HIV disclosure and non-disclosure, low health literacy rates and superstitions within cultural groups. Women who are HIV-positive also have economic concerns; some of which include cost of alternative feeding methods, and access to antiretroviral treatment drugs among other barriers.
The WHO states that in 2015, 77% of all pregnant women living with HIV globally received antiretroviral therapy to prevent mother-to-child HIV-ltransmission, although, there is no specificity to the location of these women worldwide.10 In the last twenty years, mother-to-child HIV-1 transmission rates have decreased significantly in developed nations. With the use of appropriate interventions, vertical HIV-1 transmission rates of less than 2% have been reported in European and North American populations.11 Therefore, based on transmission rates on a global scale, HIV-positive women living in developed nations are most likely receiving appropriate care to reduce risk of mother-to-child transmission of HIV. Alternatively, HIVpositive women in developing countries are not receiving the same preventative, and protective care.
Per nutrition research and data, breastfeeding provides various nutritional, immune, and long-term benefits for the infant, coupled with a variety of maternal benefits. The choice to breastfeed will pose a controversial and difficult decision for HIV-positive mothers regarding risk of HIV-1 transmission. According to the 2016 WHO updated guidelines on HIV and infant feeding, even when antiretroviral drugs are not available, HIV-positive mothers should exclusively breastfeed in the first six months of life and continue breastfeeding thereafter unless environmental and social circumstances are safe and supportive of replacement feeding
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
methods.12 In circumstances when antiretroviral therapy drugs are unlikely to be available for mothers, breastfeeding of infants is recommended to increase infant survival.12
Various global and national policy statements on the issue directly correlate to the health and welfare of HIV-positive mothers and infants in developing countries. In the United States, the general consensus is that HIV is a notable contraindication for breastfeeding.13 Generally, practitioners in the field will discourage breastfeeding with an HIV-positive diagnosis.13 The American Academy of Pediatrics stance on HIV-positive mothers and breastfeeding states that in the industrialized world, it is not recommended that HIV-positive mothers breastfeed.13 Alternatively, current global health policy and recommendations promote exclusive breastfeeding, even if HIV-positive.
Although policy is set to aid the broad population it serves, sometimes the set-forth procedures and strategies prove to be unsuccessful. For example, the greatest declines in breastfeeding have taken place in countries where infant formula has been distributed at no cost by national and local authorities in order to prevent mother-to-child HIV-1 transmission.14 Although the policy sought to improve the lives of its citizens, an unforeseen consequence of the program was that even mothers who were not HIV-positive turned to infant formula, therefore decreasing breastfeeding rates altogether.14
With a culturally appropriate understanding of these complex issues, determination of whether or not women who are HIV-positive should breastfeed will be discussed in conjunction with dissimilar global health policy in developed and developing nations. Overall, this thesis will seek to establish if breastfeeding is culturally and healthfully appropriate for mother and infant, while determining the effectiveness of current global health policy statements and recommendations.
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
Issues in Developing Countries
I. Benefits of Breastfeeding
According to The Centers for Disease Control and Preventions (CDC) most recent data: in 2011 79% of newborn infants were started on a breastfeeding regimen in the United States.15 However, breastfeeding did not continue for as long as recommended. Of the infants born in 2011, 49% were still being breastfeed at six months and only 27% at twelve months.15 For various reasons, women in the United States do not breastfeed for the recommended amount of time aimed at maximizing benefits for mother and infant. UNICEF provides data denoting exclusive breastfeeding percentages of infants 0-5 years of age (provided in the picture below).16
World
Source: UNICEF global databases, 2016, based on MICS, DHS and other nationally representative sources, 2010-2016 (*denotes countries with older data between 2005-2009: data form these countries are not included in the regional aggregates except for China (2008) which is used for the East Asia and the Pacific and World averages). Countries shaded in dark grey have estimates from 2004 or earlier: these countries are not included in the regional or global aggregates.
From the above data, speculation can be made that a greater proportion of developing countries breastfeed infants for at least five months compared to developed countries. Observing the data, only 43% of mothers worldwide breastfeed their infants exclusively for five months.16 Exclusive breastfeeding (no supplemental food or liquid) provides complete nutrition for the
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infants first six months of life, and should be continued for at least one year with complimentary food added at six months, or when the infant is developmentally ready.17
According to the Academy of Nutrition and Dietetics, breastfeeding provides the best possible nutrition for an infant because breastmilk contains factors which serve both nutritive and non-nutritive functions.18 It has been well documented that the high bioavailability of essential vitamins and minerals found in breastmilk are best served for the immature digestive system of an infant compared to alternative methods of infant feeding.18 Human milk is uniquely suited to the infant; the breastmilk changes in composition starting with colostrum to late lactation, and varies within feeds.19 Breastmilk provides growth hormone, and contains the proper ratio of protein, fat and carbohydrate, which change throughout infant growth in order to best serve the infants nutritional needs.19 Additionally, breastmilk provides maternal immune factors which help to develop the gut microbiome of the infant while also protecting against disease.18 Breastfed infants have a decreased prevalence of ear infections, respiratory illness, sudden infant death syndrome, as well as other health conditions later in life including obesity and hypertension.18 Also, Breastfeeding distinctively supports healthy brain development, increases IQ and is associated with improved educational achievement at age five-years-old and beyond.20
In addition to the numerous benefits for infants, breastfeeding also provides various maternal benefits. Immediate skin-to-skin contact and early initiation of breastfeeding after delivery can reduce risk of maternal post-partum hemorrhage while increasing compliance and ease of future breastfeeding.21 Breastfeeding additionally reduces risk of breast, uterine and ovarian cancers, and aids in weight loss after delivery for the majority of mothers.18'20 Various
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studies also suggest an association between early cessation of breastfeeding and an increase of maternal post-natal depression.20
In developing countries, the benefits of exclusive breastfeeding stretch further. In addition to the previous listed benefits for mother and infant, in developing countries early and exclusive breastfeeding significantly reduces risk of infant morbidity and mortality. According to UNICEF, a child who is exclusively breastfed is 14 times less likely to die in the first six months of life than a non-breastfed child.20 The two leading causes of infant morbidity and mortality in developing countries include acute respiratory infections and diarrhea.20 Exclusive breastfeeding drastically reduces the incidence of both.
Every year, approximately 4.9 million children between the ages of 28 days and five-years-old die, primarily in developing countries.2 Of the 4.9 million children, 28% die from
diarrhea and pneumonia (table).2
Causes of deaths in children under 5 years
(over 8 million/year)
Asphyxia 9%
Diarrhoea 14%
Preterm 12%
Pneumonia 14%
Sepsis 6%
Other infections 9%
Malaria
Noncommunicable diseases
Injury 3%
AIDS 2% Pertussis Meningitis 2% Measies
Other
neonatal 5%
Pneumonia, neonatal 4%
Congenial 3%
Tetanus 1%
Diarrhoea, neonatal 1%
Source: The Partnership for Maternal, Newborn and Child Health. Newborn death and illness.
http://www.who.int/pmnch/media/press materials/fs/fs newborndealth illness/en/. Updated September 2011. Accessed March 2,
2017.
Diarrhea ranks high on causes of infant mortality. Predominant breastfeeding would
reduce prevalence of diarrheal prevalence by about 56% in the first five months of life, and
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would reduce infant mortality attributed to diarrhea by 78% ,3 In the review article,
Breastfeeding and the Risk for Diarrhea Morbidity and Mortality, formula fed infants 0-5 months of age had a relative risk ratio of 4.90 for prevalent diarrhea when compared to partially breastfed infants who had a risk ratio of 2.15, roughly half the risk of not breastfeeding at all.3 Partially breastfeeding infants is not as preventative as exclusive breastfeeding. Partially breastfed infants are supplemented with additional food and water sources which can increase risk of diarrheal prevalence from bacterial contamination. Infants in the first five months of life who were predominantly breastfed (RR: 2.28), and partially breastfed (RR: 4.62) had a 78%-56% decreased risk of mortality from diarrheal episodes.3 Breastfeeding in any capacity reduces risk of infant death from dehydration caused by diarrhea.
In addition to diarrhea, pneumonia and other respiratory infections are also widespread causes of infant death occurring much more frequently in developing countries.2 While 14% of child deaths under the age of five can be attributed to pneumonia, breastfed infants are 47% times less likely to die of a respiratory infection such a pneumonia than non-breastfed infants. Breastfeeding is also associated with a 74% lower risk of pneumonia-related hospitalizations and a reduced risk of lower respiratory infections up to four years of age.4'5 Therefore, breastfeeding in developing countries can reduce instances of respiratory infection, as well as diarrheal occurrence, thus contributing to increased survival rates of children under the age of five-years-old.
Poor nutrition status and malnutrition account for significant rates of child and infant death annually. Over one-third of all child deaths are linked to malnurition.2 Stunting can occur from poor nutrition in the first thousand days of a childs life, and is associated with impaired cognitive ability, and an increase in frequency and severity of common infections.22 Exclusive
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breastfeeding for the first five months of life decreases the instance of stunting, wasting and malnutrition by an average of 12.2%.23 Children are not receiving appropriate nutrition early in their lives, they are therefore suffering from malnutrition, stunting and wasting.
In 2016, the majority of stunted children were localized in South East Asia, 46%, and Africa, 70%,22 Although, 57% of sub-Saharan Africa and 90% of South East Asia exclusively breastfeed for up to five months, proper nutrition after breastfeeding cessation may not be
achievable, therefore increasing malnutrition rates in poverty stricken locations for children up to
five-years of age.16 (reference picture below).
Latin America Caribbean
World
w
Past Asia and the Pacific
West and Central Africa
and
Southern Africa
Source: UNICEF, WFtO, World Bank Joint Child Malnutrition dataset, September 2016 update
Morbidity and mortality of infants and children up to the age of five frequently occur
no data
from bacterial, and respiratory infection. Both of which can be reduced considerably with exclusive breastfeeding practices. Therefore, increasing rates of exclusive breastfeeding is warranted in developing countries in order to reduce infant death. Breastfeeding is the gold standard method of infant feeding, although, certain contraindications discourage mothers from breastfeeding and health professionals from recommending breastfeeding. One prominent reason
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not to breastfeed is HIV-infectivity because the virus can be transmitted from mother-to-child via breastmilk.
II. Breastfeeding with HIV/AIDS
With high prevalence of HIV/AIDS in developing nations, specifically sub-Saharan Africa, many HIV-positive mothers are expected to make a decision to either refrain from, or initiate breastfeeding after delivery. HIV-1 can be vertically transmitted three different ways: in utero, at delivery and through breastfeeding.
Mother-to-child HIV-1 transmission has been well documented since the HIV/AIDS epidemic began. In the late 1980s early 1990s, the first reports of HIV-1 transmission via breastmilk were of infants breastfed from women who had been infected postnatally through blood transfusions or through sexual intercourse after delivery.24 Additionally, infants with no other known exposure to HIV, became infected through wet-nurses or pooled breastmilk.24 Over the last thirty-years, various research has sought to determine a statistical risk of transmission via breastfeeding, although, rates differ substantially.24
There are varying statistics delineating the risk of HIV-1 transmission via breastfeeding.
It is difficult to determine whether or not an infant becomes infected during delivery (intrapartum), or through early breastfeeding with current technological methods of HIV diagnosis.24 In the absence of any intervention, which may include antiretroviral treatment for mother and infant, elective caesarian section (C-section) and avoidance of breastfeeding, the overall mother-to-child transmission rate is approximately 20%-40%.25 Vertical HIV-1 transmission risk estimations find that 10%-25% of transmissions occur during pregnancy, 35%-40% during labor and delivery, and 35%-40% during breastfeeding.26 According to other studies, transmission rates via breastfeeding alone are between 15%-45%.8'9
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
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Observing the table below, even if an HIV-positive mother chooses not to breastfeed her child, there is still a risk of 15%-30%. This is attributed to probable intrapartum transmission, but cannot be specifically measured, therefore, rates of transmission risk via breastfeeding are many times lower.24 However, transmission rates gradually increase with added duration of breastfeeding (table 1 ).924"26
Table 1. Estimated Timing and Risk of Mother-to-Child Human Immunodeficiency Vims Type 1 (HIV) Transmission*
Breastfeeding Through Breastfeeding Through
No Breastfeeding, % 6 Months. %t 18 to 24 Months,
Timing Relative Proportion Absolute Rate Relative Proportion Absolute Rate Relative Proportion Absolute Rate
Imrauterire 2510 35 5 to 10 20 to 25 5 to 10 20 to 25 5 to 10
Intrapartum 6510 75 10 to 20 40 to 55 10 to 20 35 to 50 10 to 20
Postpartum breastfeeding Early (first 2 tnorihs) Late (after 2 months!
20 to 25 5 to 10
5 to 10 1 to 5
20 to 25 20 to 25
5 to 10
Overall
25 to 35
Rou-ced consensus esbmates by meajfocs. nayi m a nstnai'^ujj-ji nt Iteracu'e, at tre absolute transmsscn rates and oroportlor of trsnsrrr
at afferent tma pcMs m tre absence ct sntrecrMtal treeine'-:. t Postpartum trarsmason estmate at 6 months ndudes eary breastfeeding trarsmeaon ret 2 montfe), which Is Olthcult to cfistlngUsh tram imrspanum transmeaon in cublsabed aludes but Ikety accounts lor more than half of breastfeedng traramaaon in the first 6 months."
(Data are cumdattve totals; b'eastfeeoirg transmission estimates at 24 montne ndude transmission occuhng before 6 months.
Source: Cock K, Fowler M, Mercier E, de Vincenze I, Saba J, Hoff E, et. Al. Prevention of mother-to-child-transmission in resource-poor countries, translating research into policy and practice. JAMA. 2000:283:1175-1182.
Breastfeeding poses a clear risk of potential HIV-1 transmission from mother to infant, depending on duration and method of feeding associated. Many mothers would prefer not to breastfeed their child for fear of infecting them with HIV-1. Although, if not breastfed, the infant will then be more likely to die of respiratory or diarrheal disease. The choice to breastfeed while HIV-positive increases the risk of infants contracting a fatal, and chronic disease. However, the increased chance of infant survival from the benefits of breastfeeding will therefore pose a difficult decision for any HIV-positive mother.
HIV/AIDS is a historically relevant issue across Africa and other developing nations.
HIV (human immunodeficiency virus) can lead to AIDS (acquired immunodeficiency syndrome). Chronic HIV ranges in symptoms of weight loss, diarrhea, high fever, and can progress to more severe symptoms with AIDS.27 HIV/AIDS is not curable, only treatable. HIV
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attacks the bodys immune system, specifically targeting CD4 (T cells), which help the immune system fight off infections.27
If left untreated, HIV reduces the number of CD4 cells in the body making a person more likely to develop infections or infection-related cancers.27 Over time, HIV can destroy so many CD4 cells that the body is unable to fight off infections and disease.27 These opportunistic infections or cancers take advantage of a persons weak immune system. When the immune system is so drastically altered and CD4 cell count falls below 200 cells per cubic millimeter of blood (200 cells/mm3) the person is then considered to have AIDS.27 AIDS is also diagnosed when a person develops one or more opportunistic infections, regardless of CD4 cell count.27 HIV can progress to AIDS within 10 years without appropriate treatment in any population.27
The prognosis for someone who is diagnosed with AIDS is roughly around three years.27 If the opportunistic infections are dangerous, life expectancy falls to about one year.27 There is no effective cure for AIDS currently, but with proper treatment and medical care, HIV can be controlled and antiretroviral therapy can prolong the lives of people living with HIV, as well as decrease rates of transmission in any context.27'28
Infants in particular can benefit from antiretroviral therapy drugs. Research suggests that if infants are tested at six-weeks postpartum, and on treatment by twelve-weeks postpartum, there can be a 75% reduction in infant morbidity and mortality due to HIV/AIDS.29
National governments, and external donors (U.S. and other developed countries) have attempted to supply antiretroviral medication targeting the HIV-positive maternal-infant population in order to reduce vertical transmission rates.30'31 Even though attempts have been made to decrease the rate of vertical HIV-1 transmission, looking specifically at South Africa, preventative measures have not had the impact the government was expecting. According to
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UNAIDS, in 2014 6.8 million people were living with HIV in South Africa, 3.9 million were females over the age of 15.32 The WHO states that in 2014, 263,674 women in South Africa received antiretroviral medication in order to prevent mother-to-child HIV-1 transmission, although, this is only 6.7% of the female HIV-positive population.33 Assumptions can be made that more than 6.7% of the female HIV-positive population is reproducing, therefore there is still likely risk of vertical HIV-1 transmission even with efforts to distribute antiretroviral medication to this at risk populations.
The prognosis for someone with limited or no access to appropriate healthcare is not favorable. Therefore, in order to decrease vertical HIV-transmission risk via breastfeeding, many HIV-positive mothers use alternative methods of infant feeding. Infant formula, cow and/or goat milk, or heat-treating expressed breastmilk, are all alternatives to breastfeeding, but have specific risks associated to each method.
III. Alternative Methods of Infant Feeding
Many HIV-positive women living in sub-Saharan Africa come from very low socioeconomic status, which makes obtaining safe alternative infant feeding products difficult because of financial constraint. Looking specifically at South Africa, an endemic area that has the largest prevalence of HIV/AIDS, the household median income for the black African population is roughly between R60,000 ($4,459.14 USD) and R34,078 ($2,532 USD) per year.34 Half of all black Africans are earning below, and half are earning above this estimate annually. Black Africans make a sixth of the household income of a white family, but make up 80.2% of the overall population.34'35
Using the low end of median annual income per black African household in South Africa at roughly R34,100 ($2,534 USD), the average monthly income averages out to about R2,841.66
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($211.14 USD). The price of infant formula in South Africa ranges from R47.95 (3.74 USD) to R4,161.00 (324.19 USD).36 The most common infant formulas purchased in South Africa are starter formulas, most frequently Nan which is produced by Nestle.37 The cost of Nan Stage 1 Starter Infant Formula (900g) is R157.00 ($11.68 USD).38
As a single example, an infant during the 2nd and 3rd months of life requires seven scoops per day of the Nan Stage 1 Starter infant formula mixed with water.39 In a single day an infant should receive 4-5 feedings which aggregates a range of around 100g-130g of infant formula per day. In one week a mother utilizing Nan Stage 1 Starter Infant Formula should use between 700g and 900g of infant formula. In a little over one week, the infant formula should be fully utilized.
With an average monthly income of R2, 841.66 ($211.14 USD), purchasing infant formula once per week will consume roughly 22% of the monthly household income. Infant formula will become more expensive as time progresses until around six months of age, or when the infant is developmentally ready for the addition of complementary foods. The cost of almost $12.00 USD per week for infant formula may not seem like a substantially high number, although, the cost of living in South Africa is relatively high, an example of the average cost of 1 gallon of milk is R50.69 ($3.77 USD)40 Consequently, there is little room for extra expenses. Infant formula as a substitute for breastfeeding may not be a feasible and cost effective alternative for some HIV-positive mothers and/or families.
The median income for a black African household is low, and the cost of infant formula is quite high, therefore, some mothers will use infant formula on the basis of quantity rather than quality. This stems from lack of knowledge about proper infant feeding, or lack of knowledge regarding the infants nutritional needs.41 The mother may neglect proper infant feeding
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recommendations, and make the infant formula last as long as possible by watering the amount of infant formula down, causing dilution. These mothers may not realize that the infant is not receiving the appropriate nutritional requirements needed for growth.41 The child may then be classified as non-organic failure to thrive, therefore increasing chance of protein energy malnutrition and infant death. This method of feeding is extremely dangerous.
While it is necessary to utilize water to mix infant formula, this may cause deadly barriers for many women of low socioeconomic status in developing countries. If infant formula is used as a replacement feeding method, infants are at increased risk of death from bacterial contamination causing diarrhea and therefore death by dehydration.
According to the United Nations, in 2012 there were 748 million people relying on unsafe water sources, 173 million people obtained their drinking water straight from rivers, streams or ponds.42 However, unclean water and sanitation is predominantly localized in rural and poverty-stricken areas; seven out of ten people without access to sanitary facilities live in rural areas.42 Many drinking water sources are not easily accessible to numerous households in developing countries and are microbiologically contaminated, consequently increasing risk of diarrheal episodes in infants who are consuming the water several times per day 42
International organizations, such as the WHO, USAID and the World Bank have increased programs to thwart unsafe drinking water and increase hygienic practices specifically in HIV/AIDS endemic areas.43'47 Through these programs, there have been instances of reduced bacterial contamination thus decreasing diarrheal episodes. A trial in Uganda found that household chlorination technology in HIV-positive households had a 25% reduction of diarrheal episodes, and 33% fewer days with diarrhea compared to the control group.48 Additionally, significant associations with diarrhea reduction and chlorination technology have been found in
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Nigeria among adults with HIV/AIDS and in Kenya regarding infants born to HIV-positive mothers.49'50 Conversely, these programs have typically been in the form of chlorination products, which do not inactivate or kill the extensive diversity of waterborne pathogens.51 Therefore, the use of disinfectants alone cannot be expected to eliminate all bacterial waterborne pathogens.
Although there has been an increase in drinking water chlorination technology aimed at reducing bacterial contamination, there is evidence to assume that more needs to be done in order to reduce diarrhea caused by bacterial pathogens in drinking water.
In a random-cluster household survey study conducted in Abidjan, Cote dIvoire, a collected source of stored drinking water samples were tested for chlorine levels and fecal bacteria count in 120 households.52 Although 93% of the study population utilized municipal water for drinking, 83% of the population stored it for later use.52 Approximately 90% of the 108 infants by one month of age who were given drinking water, were given the stored water.52 In 12 of the households 66% of infants were receiving infant formula prepared with the municipal water without additional treatment.52 The stored water had lower levels of free chlorine than the source water, and E. coli was detected in 41% of 87 stored water samples, but only in 1% of 108 source water samples (Table l).52
TABLE 1. Frequency of coliform bacteria and Escherichia coli in water samples. Abidjan. Cote d /wire
Source water Stored water
Result n = 108 (%) n 87 (%)
Coliform bacteria 2 (2) 64 (74)
Escherichia coli 1(1) 36 (41)
Source: Dunne E, Angoran-Benie H, Kamelan-Tano A, Sibailly T, Monga B, Kouadio L, et al. Is drinking water in Abidjan, Cote dIvoire, safe for infant formula? JAcquire Defic Svndr. 2001:28(4):393-8.
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Although municipal water is provided to this community as a source for safe drinking water, the majority of the population stored the water for later use which included infant formula. Storing municipal water consequently perpetuates bacterial contamination and increases risk of diarrheal episodes in the infant population and therefore morbidity and mortality.
Unsafe drinking water is a significant cause of death, especially for infants of low socioeconomic status. People with HIV/AIDS are extremely susceptible to opportunistic infections from waterborne pathogens, therefore safe water is critical for HIV-positive mothers who choose to utilize infant formula as a replacement feeding method. In the study, Drinking Water Quality, Feeding Practices, and Diarrhea among Children Under 2 Years of HIV-Positive Mothers in Peri-Urban Zambia, 26% of children under two years of age had diarrhea in the past week and bacterial contamination of drinking water was found in 70% of households.53 The risk of death from diarrhea caused by contaminated water may outweigh the risk of HIV-transmission via breastfeeding in the majority of low socioeconomic settings, particularly in developing countries.
Additionally, the use of cow milk is an inappropriate alternative to exclusive breastfeeding and is dangerous. Cow milk is for baby cows, not baby humans. There are varying differences between human milk and cow milk. If cow milk is used as the primary, or only form of replacement feeding, certain nutritional issues and deficiencies will arise. According to a case-control study in Batswana (below picture), approximately 40% of infants were receiving neither breastmilk nor formula, but instead received a variety of substitutes including pasteurized and unpasteurized cow milk.54
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
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£
S
B
n
%
*
a
X
LU
100%-75% < 50% -25% < 0% <
HIV-
HIV*
M*ZS N-1*
Maternal HIV status
Other
Formula feeding
Breast feeding
Source: Arvelo W, Kim A, Creek T, Legwaila K, PuhrN, Johnston S, et al. Case-control study to determine risk factors for diarrhea among children during a large outbreak in country with a high prevalence of HIV infection. IJID. 2010;14:el002-el007.
In 1 fluid ounce of whole cow milk, there are 2 kilocalories less than in human breastmilk, with 33% more protein.17 The protein in cow milk is significantly different from human breastmilk. The predominate protein found in cow milk is casein, which accounts for about 80% of total protein.55 Conversely, in human breastmilk, whey protein accounts for 60-70% of total protein.55 Whey protein is more easily digestible than casein protein, and actively protects against bacteria, therefore decreasing risk of bacterial infection while increasing infant immunity.17'55
Additionally, lipid profiles vary among human and cow milk. In cow milk, saturated fatty acids account for the majority of fat composition, where unsaturated fatty acids account for the majority of fat composition in human breastmilk. Cow milk is also higher in sodium, potassium and phosphorous than in human breastmilk.17 The high electrolyte composition in cow milk is difficult for an infants premature kidneys to effectively process. The renal solute load of high electrolyte concentrations coupled with the high casein protein in cow milk leads to a higher urine osmolar concentration three times higher than that of human breastmilk.56 The renal concentrating ability of an infants kidneys may be insufficient for maintaining water balance, and therefore severe dehydration may result.56
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Cow milk also differs in micronutrient composition. The bioavailability of micronutrients found in cow milk are not as bioavailable as micronutrients in human breastmilk.17 In lOOg of cow milk, there is <5mg of iron, and only about 10% of the <5mg of iron is absorbed by the infant.57 There is also no ascorbic acid (vitamin C) in cow milk. Vitamin C increases iron absorption, therefore lack of vitamin C perpetuates the low bioavailability of iron found in cow milk. Furthermore, cow milk forms a curd in the stomach of infants causing bleeding and occult gastrointestinal blood loss blood which is not visible in fecal stool samples. Occult gastrointestinal blood loss happens in roughly 40% of infants fed cow milk.58 The combination of no vitamin C, occult gastrointestinal blood loss, and low bioavailability of iron directly contributes to higher potential of developing iron deficiency anemia.
In comparison to cow milk, goat milk has approximately the same nutritional composition, with a few notable differences. In general, goat milk contains less lactose, fat and protein than cow milk, but has similar mineral and electrolyte content.59 The most notable difference between the two is the lack of folic acid in goat milk. In addition to the other risk factors listed previously concerning cow milk, the lack of folic acid in goat milk will cause megaloblastic anemia, therefore increasing infant comorbidities, and potential infant death.60
The nutritional composition of both cow and goat milk pose distinctive, individual risks. There are also non-nutritive risks to use of cow or goat milk as alternative feeding methods. A primary issue with both breastmilk substitutes is the use of unpasteurized products which contribute to an increased risk of food borne illness.61 Pathogens commonly transmitted through food disproportionately impact children younger than five years old.62 The child and infant population faces higher risk of foodbome pathogen exposure because their immune systems are less developed, and have limited ability to fight infections.62 Additionally, an infants lower body
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weight reduces the amount of pathogen needed to cause illness.62 If these infants are not breastfed, risk of infection increases because maternal immune factors are not present to protect against pathogens.
The WHO estimates that approximately 125,000 children under the age of five years old die annually from foodborne illnesses, with the highest burden in African and South-East Asian populations.63 This accounts for almost 30% of all deaths attributed to foodborne illnesses globally, despite the fact that children under five-years-old make up only 9% of the global population.63 Most notable pathogens include bacteria, viruses, helminths, toxins and chemicals.63 Around 220 million children under the age of five fall ill, and 96,000 die every year from foodborne diarrheal pathogens including: norovirus, Campylobacter, non-typhoidal Salmonella and pathogenic Escherichia coli63 Diarrheal diseases are responsible for roughly 70% of foodborne illnesses in the African region, of which Salmonella specifically causes the most deaths.63
Raw or unpasteurized milk products carry dangerous bacteria including Salmonella, Escherichia coli and Listeria throughout the world.64 These pathogens can cause adverse health effects in anyone consuming the raw product. Unpasteurized milk can be even more dangerous to pregnant women and children, especially with weakened immune systems caused by HIV/AIDS.64
In addition to the issues of unpasteurized milk products, other limitations arise. Women who are using cow and/or goat milk as an alternative to breastmilk need to consider the cost associated as well as access to appropriate storage and refrigeration. As a single example, in a periurban settlement in South Africa, 70% of eighty-four HIV-positive mothers did not have
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES
access to refrigeration.65 Lack of refrigeration increases risk of further contamination of cow and goat milk.
Heat-treating expressed breastmilk is another alternative method of infant feeding. Heating expressed breastmilk to a high temperature in a very short amount of time can be done with simple tools in a home setting. This method of alternative infant feeding is a feasible and safe option for many HIV-positive mothers. Flash-heating expressed breastmilk retains the majority of the breastmilks nutrient profile and maternal immune factors, while killing the HIV-1 virus.
In the study, Vitamin Content of Breast Milk from HIV-1-Infected Mothers Before and After Flash-Heat Treatment, fifty HIV-positive mothers in Durban, South Africa manually expressed 75-150 mL of breastmilk into sterile jars.66 The milk was allocated to unheated controls or flash-heated.66 The samples were then analyzed to determine the micronutrient concentrations in unheated and flash-heated expressed breastmilk.66 Vitamin A was not significantly affected by the flash-heating method, however, vitamins Bu, C and folate increased.66 In contrast, vitamins B2 and B6 were decreased to 59%, than that of unheated milk.66
O
(/)
u>
o
c
o
c
o
c
o
o
Vitamin A Ascorbic Riboflavin Pyridoxal 5 Folate B12
retinol Add (ug/L)** phosphate (ug/L)*** (ng/L)
(ug/dl) (mg/dl) * B6 (ug/L) **
Vitamin
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Source: Israel-Ballard K, Abrams B, Coutsoudis A, Sibeko L, Cheryk L, Chantry C. Vitamin content of breast milk from HIV-1-infected mothers before and after flash-heat treatment. JAcquir Immune Defic Syndr. 2008;48(8):444-449.
It is hypothesized that the post-heat increase in ascorbic acid, folate and vitamin Bi2 concentrations compared to unheated samples can be caused by heat-induced release of vitamins from binding proteins in the breastmilk.66 The vitamins above were selected in the study because of their essential role in the maternal-infant dyad during lactation.66
In addition to micronutrient composition being relatively unchanged in flash-heated breastmilk samples, the majority of maternal immune factors are also retained. Fifty HIVpositive mothers in South Africa provided breastmilk, part was unheated as a control, and the remainder was flash-heated.67 Total antigen-specific IgA and IgG were measured to detect the amount of maternal immune factors kept intact after flash-heating breastmilk samples.67 In fifty analyzed samples, flash-heated breastmilk induced a statistically significant decrease in total IgA (20%), and a decrease in IgG (33%).67 Although there is a notable reduction of maternal immune factors in flash-heated breastmilk samples, most maternal immune factors in breastmilk survive.67 Therefore, flash-heating breastmilk is far superior to other breastmilk substitutes because most maternal immune factors are kept intact.
The use of flash-heating expressed breastmilk kills the HIV-1 virus. In order to inactivate both cell-free and cell-associated HIV-1, temperature of the breastmilk needs to reach at least 65C, but not over 70C, in order to retain breastmilks nutrient composition and maternal immune factors.68 In the study, Flash-Heat Inactivation ofHIV-1 in Human Milk, ninety-eight breastmilk samples were collected from eighty-four HIV-positive women located in South Africa.69 The breastmilk was either unheated as a control, or flash-heated. Reverse transcriptase assays were used to detect active and inactive cell-free HIV.69 All flash-heated samples showed undetectable levels of cell-free HIV-1.69 The use of flash-heated expressed breastmilk can
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effectively inactivate HIV in infected breastmilk.69 Heat-treating expressed breastmilk as an alternative method of infant feeding may be a feasible option for HIV-positive women that carries virtually no risk of mother-to-child HIV-1 transmission, while providing the many benefits of breastmilk.
Heat-treating expressed breastmilk does pose potential limitations and risks regarding compliance, methods and storage. There is an eight-point protocol regarding heat-treating expressed breastmilk: 1) wash hands with soap prior to expressing; 2) clean jar and feeding cup with soap; 3) sterilize jar and feeding cup by boiling; 4) express milk into glass jar; 5) express from both breasts; 6) place the jar in a pot with sufficient water to come two finger-widths above milk level and heat until water reaches a rolling boil; 7) remove pot as soon as water boils; 8) immediately remove jar from pot and cover.70 Mothers are then instructed by nursing personnel and other health professionals to feed the heat-treated expressed breastmilk within eight hours, which is the shelf life at room temperature.71 Many people live without access to refrigeration and cannot appropriately store the expressed heat-treated breastmilk, therefore making this option a less likely candidate for alternative feeding methods if proper storage cannot be attained.
If HIV-positive mothers do not adhere or comply with all eight steps listed above, risk of negative outcomes may arise. If women do not have access to soap and clean water for washing hands before expressing and to wash feeding cups and other vessels, risk of bacterial contamination increases. If mothers do not heat the expressed breastmilk for the appropriate amount of time HIV-1 virus will still be present. If heated too long, or at too high of a temperature, the micronutrient and maternal immune factor composition of the breastmilk will
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
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decrease. Therefore, compliance is necessary in order to use heat-treating expressed breastmilk as an alternative infant feeding method.
Certain cultural taboos and superstitions may also play a role in the use of heat-treating expressed breastmilk. In the study, Acceptability of Heat Treating Breast Milk to Prevent Mother-to-Child Transmission of Human Immunodeficiency Virus in Zimbabwe: A Qualitative Study, seventy-seven study participants (men and women who did not disclose HIV status) participated in thirteen focus group discussions in three demographic regions of Zimbabwe.72 Focus groups discussed topics including: the current practice and understanding of manual expression of breastmilk, knowledge of flash-heating as a method to reduce mother-to-child HIV-1 transmission, cultural perceptions, and required resources. Discussion topics also referenced community and financial support, education or counseling regarding heat-treating expressed breastmilk, and the overall potential to accept this as a an alternative method of infant feeding.72 While 30% of female participants noted that they had expressed breastmilk at some point during lactation, only 6% of participants were aware that heat-treating expressed breastmilk could prevent HIV-1 transmission 72
Most participants, male and female, were concerned that manually expressing breastmilk would disrupt the bond between mother and child, which would otherwise strengthen if breastfeeding 72 Participants believed that only a breastfeeding child was capable of recognizing its mother by touch, voice, and smell.72 In rural and suburban settings, the most commonly cited belief was that a non-breastfed infant was acting as a prophet to reveal that either the mother or the father had been unfaithful.72 In various areas of Zimbabwe, infants who refuse to nurse, and thus receive expressed breastmilk, are said to suffer until a mother confesses her wrongdoing.72 Furthermore, women who are non-breastfeeding and express breastmilk, are also viewed as
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witches. A lot of suspicion will be raised people may think the women is a witch and wants to feed her breastmilk to snakes, goblins, and hyenas.72
Another notable cultural taboo in all groups involved in the study is the concept of one becoming contaminated by touching human milk. Vessels that hold expressed breastmilk, including bottles, cups or pots are then considered contaminated.72 This now contaminated vessel could affect anyone entering the home according to several midwives and birth attendants in the study.72
The negative social implications of heat-treating expressed breastmilk as an alternative to breastfeeding in order to reduce, or potentially eliminate the risk of vertical HIV-1 transmission via breastfeeding are serious. With these health beliefs, certain consequences can arise including the community accusing the women of being a witch or adulterer, thus causing these women to be stigmatized and ostracized within their communities and families. The graph on the following page depicts the percentage of people in the study who correlated expressing breastmilk to witchcraft, contamination, or adultery.
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Figure I. Culiur.il iwuos voiced by participants surrounding the expression of breast milk by groups and demographic regions.
Source: Israel-Ballard K, Maternowska C, Abrams B, Morrison P, Chitibura L, Chipato T, et al. Acceptability of heat treating breast milk to prevent mother-to-child transmission of human immunodeficiency virus in Zimbabwe: a qualitative study. J Hum Lact. 2006:22(l):48-60.
In some communities the use of flash-heating expressed breastmilk to aid in reduction of vertical HIV-1 transmission via breastfeeding may be the best option. Although, in other communities, such as parts of Zimbabwe, it may not be socially and culturally appropriate. Overall, with proper education and accessible methods for compliant flash-heating of expressed breastmilk, this option may be extremely beneficial in certain populations.
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Some mothers may consider partially breastfeeding by using an alternative method of infant feeding in addition to breastfeeding to reduce cost while also trying to reduce mother-to-child HIV-1 transmission. HIV-positive mothers may assume that there is a decreased risk of transmission if they are not exclusively breastfeeding. Although, this mixed method of feeding is dangerous and can actually increase risk of mother-to-child HIV-1 transmission via breastfeeding.73
It has been suggested that exclusive breastfeeding with HIV could be associated with decreased risk of HIV-1 transmission, compared to mixed feeding methods of both breastmilk and an alternative method of infant feeding. In Durban, South Africa, a prospective cohort study looked at the risk of HIV-1 transmission by infant feeding modality. A total of 551 HIV-infected women self-selected to breastfeed or formula feed after being counseled to breastfeed for 3-6 months.74 Of the 551 HIV-positive women, 157 formula fed, 118 exclusively breastfed, and 276 used mixed methods of feeding.74 Infants who received both breastmilk and alternative feeding methods were more likely to be vertically infected via breastfeeding by 15 months of age (36%), than infants exclusively breastfed for at least three months (25%), or infants who had been exclusively formula fed (19%).74
Fig. 1. Cumulative probability of detecting HIV infection over time among 157 children who were never breastfed (-----------), 118
exclusive breastfeeders (----), and 276 mixed breastfeeders (------).
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Source: Coutsoudis A, Pillay K, Khun L, Spooner E, Tsai W, Coovadia H, et al. Method of feeding and transmission of HTV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS. 2001;15:379-387.
The attributed cause of increased risk of vertical HIV-1 transmission by mixed feeding methods has been hypothesized, yet nothing has been confirmed. It has been theorized that the association can caused by increased gastrointestinal permeability, or local inflammation in the infant.74 Another hypothesis is an increase in subclinical mastitis. It is thought that women who are continually mix-feeding their infants may be practicing suboptimal breastfeeding practices, and therefore have a higher association of subclinical mastitis thus increasing risk of vertical HIV-1 transmission via breastfeeding.75 As discussed previously, the use of alternative feeding methods will increase risk of comorbidities, therefore increasing the risk of infant morbidity and mortality. Even if a woman is HIV-positive, exclusive breastfeeding is the best option to decrease infant morbidity and mortality.
IV. Stigma Association
Ones HIV status disclosure is important in coping with the disease and understanding the surrounding implications of the chronic condition. In order to prevent HIV/AIDS and mitigate its impact, disclosure is critical. The use of alternative feeding methods also poses a substantial risk to HIV-positive mothers in a different context. In countries where HIV/AIDS is widespread, stigma greatly complicates treatment and prevention.
The stigma associated with an HIV/AIDS diagnoses often motivates people to avoid disclosing their HIV status. Disclosure of HIV status can promote stigmatization causing people to be frequently ostracized from their homes and communities. Additionally, HIV related stigma is associated with higher levels of depression, and lower quality of life overall 76 It has been estimated that over 50% of mother-to-child HIV-1 transmissions globally can be attributed to the cumulative effect of stigma 77
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Many HIV-positive women do not disclose their HIV status to their partners, family and friends which creates potential barriers to preventing perpetual sexual transmission to partners, as well as gaining appropriate care in reducing vertical HIV-1 transmission via breastfeeding.
For many HIV-positive women, there are several reasons why they may not want to disclose their HIV status, and several reasons why they do.
Looking specifically at a qualitative study involving 239 recently diagnosed HIV-positive pregnant women in Tshwane, South Africa, about 59% of the women in the study disclosed their HIV status to at least one person other than a healthcare provider, while 41% had not done so.76 The most common reason women decided to disclose their HIV status, specifically to a partner, was to inform them of infection risk, 30% decided to do so because a sense of responsibility or obligation because of the relationship.76 The most recurrent reason to disclose HIV status to parents (52.5%), other relatives and family (59.2%), and friends (82.9%) was because the women in the study thought of these relationships as supportive and trusting.76 Of the women who disclosed to their parents, many felt they needed to do so because they owed their parents the truth, and others disclosed to explain their behavior, illness and future death, I wanted them to know what killed me and asked them to look after my children when I am dead.76
Although there are reasons women disclose their HIV status to friends, family, and partners, many women make the challenging decision not to disclose their HIV status. One of the most common reasons for non-disclosure to partners in this specific South African population can be attributed to fear. Of 151 women, 31.8% did not want to disclose their HIV status because they were fearful of abandonment, blame/anger, violence, emotional abuse, and discrimination from their partners.76 As an example, one women in the study states, I do not know how to tell
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
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him [partner]. He often says he would kill me if I told him that Fm infected because he does not have HIV.76
A large proportion of these women (27.8%) did not want to disclose because they were not emotionally ready, or were waiting for either the delivery of the baby, their partners test results, or wanted to discuss the issue in person.76 Only 2.6% intended not to tell their partner at all.
The women in this study tended to be protective of their parents, My mother is sick. She had a stroke. I cant tell her because it will affect her health., approximately 22% of 261 participants, felt similarly.76 Additional reasons for non-disclosure to parents included fear (16.1%) mostly in the context of emotional abuse and discrimination.76 Overall, most women in the study were unaware of effective ways to disclose their HIV-positive status to others. One common trend among this study population, was that fear was a prominent indicator for lack of disclosure.76
When women did disclose their HIV status, only 11.9% of their partners were supportive, while 30.5% of partners were in denial or disbelief, or shock (14.6%).76 Roughly 36.7% of parents were supportive of their daughters disclosure, however, 36.7% were saddened, hurt and fearful for their child.76 Of the 173 HIV-positive pregnant women who did disclose their HIV status, 20.2% experienced some kind of adverse consequence. The most frequent adverse reaction was feeling upset by negative feedback from people they disclosed to. A small number of women experienced serious negative consequences including being abandoned by their partner, physically hurt, or threatened with death.76
HIV disclosure has risks and benefits associated, although, involuntary secondary disclosure can lead to negative experiences as well. For a variety of mothers who disclose, they
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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV-1 TRANSMISSION VIA
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are driven by the desire to ensure adequate infant care and avoid vertical HIV-1 transmission. Primary disclosures, of which the HIV-positive mother discloses to family, a partner, or friends, are usually constructive. Conversely, a breach in confidentiality leading to involuntary secondary disclosures usually result in rejection, stigmatization and the withholding of financial support from partners or partners families.76
Various social factors in the context of disclosure patterns greatly impact this subset of women. Disclosure can be shaped by social norms, media influence, political environment, household composition and other social networks.76 These factors can restrict disclosure, or alternatively provide a safe place to disclose HIV status. Media plays a significant role in mothers disclosure. With South Africa having one of the highest rates of HIV/AIDS, the South African governments management of the epidemic has received regular coverage on radio, television, and other media forms.78 This may facilitate a mothers disclosure by non-direct means. In the qualitative study, HIV-disclosure in the Context of Vertical Transmission: HIV-Positive Mothers in Johannesburg, South Africa,
My sister used to dislike people [infected] with HIV. We were listening to this radio program [about people living with HIV] and I said I didnt like the way she was talking about the people they were interviewing. I said, Dont speak badly about these people. You yourself dont know where you stand [you yourself could be infected]. Some of us have had to face this [issue of living with HIV] already. I think she realized after that [that I am HIV positive].78
By voluntarily disclosing by means of proxy, this mother did not need to have a discussion about her HIV status. She feared that if she discussed it head-on it could lead to issues she did not want
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to pursue, such as death, or blame for infection.78 There are many mothers in the same situation who prefer to disclose voluntarily by way of the media.
There can be consequences from instances of involuntary disclosure of HIV status. Most women included in the previous study described negative consequences (67.6%) which included emotional rejection, ostracism, and withdrawal of financial and other forms of material support.78 Some women reported a strengthened bond between her and her partner, although, 27% described their partners struggle in coming to terms with their HIV status, and 13.8% had deserted them or cut off financial support78 Several mothers in the study stated their family members seemed beyond responsive- termed over care. This term of over care delineates the family member(s) providing close attention to the infected individual, causing the person to feel self-conscious, trapped and isolated.78 As said by a twenty-nine-year-old mother,
[My husbands family] started separating out my things from the rest...They would lay everything out for me, saying they wanted to make sure I had everything [I needed], I had my own plates and cups and they would say Here use this. Just use it and wash it right away. They tried to be polite and caring but I could see it [my HIV status] made them uncomfortable...On my side [of the family] they are too [heavy emphasis] supportive. They are too concerned. They are always asking me Are you okay? Are you getting sick? So now I have started feeling guilty...they are too focused on me. [I feel as though] my life is no longer [my own].78
Although the family is trying to be attentive to the care of this mother, over care may cause severe negative psychological affects, and diminish the relationship in the long-run. The majority of the mothers in this study voluntarily disclosed their HIV status, which contributed to an extremely low 8.7% rate of vertical transmission by means of breastfeeding avoidance.78
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Disclosure not only reduces burden for HIV-positive mothers, but also empowers them by providing a platform to seek out and practice appropriate care to reduce vertical HIV-1 transmission. Although, for many women disclosing HIV status immediately promotes stigmatization and ostracism in their families, and communities.
Avoidance of breastfeeding in many places and cultures automatically marks a woman as HIV-positive by her family and community. There are a variety of reasons HIV-positive mothers choose certain infant feeding modalities. Factors of determination may include: cost of infant formula, influence from health workers, influence from relatives, stigma influencing nondisclosure of HIV status, and difficulties of maintaining exclusive breastfeeding or exclusive replacement feeding.79
Many HIV-positive mothers would prefer to utilize infant formula as an alternative method of infant feeding, although, because of the cost, decide to breastfeed. In addition to the cost of formula feeding, this option would ultimately disclose the mothers HIV status. A mixed qualitative and quantitative study consisting of interviews and focus groups with 811 Zambian mothers focused on infant feeding decisions, disclosure and stigmatization. Various comments were made regarding the associated stigma and disclosure of HIV status,79
I can buy milk, I can buy formula. Now I do not want to because my neighbor will be asking me, why are you not breastfeeding? And why have you stopped? [breastfeeding] at 6 months because nowadays most people know that if you stop at 6 months it means you are not okay [HIV positive].
I feel ashamed that if my friends see me giving milk to the baby they will know [my status], so it is better I breastfeed. This is what is happening most of the time to the mothers.
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. and found to be HIV-positive they fail to tell their husbands ... so in the process of hiding [the results] from husbands, you find that the husband has a good job, can even manage to buy milk for the baby but because they want to hide their status from their husband you find that they will be breastfeeding the baby. So such mothers say we are protecting our marriages because if my husband gets to know I will be chased.
The stigma associated with replacement feeding and HIV status is prominent. This poses risk for any HIV-positive mother who chooses to use an alternative method of infant feeding in order to protect her child from HIV/AIDS. Women who do not breastfeed are at great risk of being stigmatized, they risk ostracism from their partner, family and community, while simultaneously increasing risk of depression and low quality of life.79
In order to decrease stigma associated with HIV and replacement feeding, better education and promotion of breastfeeding in many circumstances will empower mothers to make appropriate and healthful feeding choices for their infants. Additionally, health workers should be educated on the respective policy of their country, and the feeding methods which are suitable for the at risk population. Overall, stigma plays a noticeable role when mothers are deciding whether or not to breastfeed their child. If mothers do not breastfeed and choose to utilize alternative methods of feeding, they have an increased risk of stigmatization among other negative outcomes.
V. Factors Which May Effect Vertical HIV-1 Transmission
For many HIV-positive mothers, breastfeeding is the only affordable, accessible, and safe method for infant feeding. If an HIV-positive mother chooses to breastfeed her infant there are considerations to take into account. Maternal nutrition and health status influence HIV-1 transmission via breastfeeding. Various comorbidities have been shown to increase vertical HIV-
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1 transmission via breastfeeding, and well as certain micronutrients when supplemented to HIVpositive pregnant and lactating women.
According to the review article, The Role of Co-Infections in Mother-to-Child Transmission of HIV, there are a variety of comorbidities (co-infections) which affect the mechanisms of mother-to-child transmission of HIV-1 in utero, at delivery and through breastfeeding.80 Considering comorbidities that affect transmission rates via breastfeeding, there are many.
A comorbidity of mastitis, increases mother-to-child HIV-1 transmission by increasing viral load in breastmilk. Breastmilk contains cell-free HIV inhibitors, because of the milk-blood barrier, concentrations of HIV are typically 10-100 times lower in breastmilk than in plasma, however, infection and inflammation of breast tissue can increase viral load in breastmilk significantly.81 The increase in breastmilk viral load increases risk of postnatal mother-to-child transmission. Roughly 10%-33% of women experience mastitis, typically during early breastfeeding, mixed feeding and during the weening stages of lactataion.80 Clinical mastitis and subclinical mastitis differ and are classified based on the degree of inflammation in the mammary glands. Clinical mastitis may be characterized by cracked nipples, sores, pain, swelling, and redness. Cracked nipples and sores frequently bleed during breastfeeding, therefore increasing the infants exposure to plasma HIV, of which viral cells are higher than in breastmilk alone.82
Similarly, subclinical mastitis is characterized by an elevated leukocyte count, elevated sodium or elevated sodium/potassium ratio and is much more common.80 Both clinical and subclinical mastitis can alter the cellular tight junctions which regulate breast epithelial permeability.80 Research has suggested that up to 50% of postnatal HIV-1 transmissions can be
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attributed to some form of subclinical mastitis.83 If an HIV-positive mother does develop mastitis or an abscesses, she must express milk from the affected side frequently and discard it and continue feeding from the unaffected side.84
In sub-Saharan Africa, and many other places worldwide, it is common practice for mothers to pre-masticate food given to infants during the weaning period, or if not exclusively breastfeeding.85 There have been various studies that note infants becoming infected with HIV who were previously HIV-negative, yet had only been given food that was pre-masticated by an HIV-positive mother or caregiver.80 In these cases, the HIV-positive mothers or caregivers had evidence of bleeding gums: gingivitis. It is contraindicated for HIV-positive mothers and caregivers to pre-masticate food with poor dentition, as it can increased risk of transmission. If an infant has oral thrush, oral sores, or bleeding in the oral cavity, risk of HIV-1 transmission via breastfeeding increases.86
HIV progression has been associated with low serum concentrations of micronutrients, intestinal abnormalities and a continuous inflammatory state throughout the body.87 Many micronutrient deficiencies are apparent within underdeveloped countries and HIV-infected populations. Micronutrient deficiencies can impair immune response, and is associated with accelerated disease progression in the HIV/AIDS population.88 Current research suggests that adequate vitamins B, C, E, and folic acid (an additional B vitamin) have been shown to delay the progression of HIV and reduce mother-to-child transmission.87 B vitamins are essential in the human body and immune system. Riboflavin (vitamin B2) deficiency decreases the humoral antibody response, vitamin B6 deficiency reduces maturation of lymphocytes, and vitamin Bi2 deficiency impairs the function of neutrophils.89 People living with HIV could improve survival with increased intake of B vitamins overall. In various studies, high serum levels of vitamin Bi2,
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Bi, B2, B6, and niacin were all associated with improved survival and delayed HIV progression.90'91 The overall survival time of patients using vitamin B supplements were significantly longer than of those not supplementing with B vitamins in HIV-positive populations.90
According to various studies, ascorbic acid (vitamin C) and tocopherol (vitamin E) were found to be lower among people living with HIV.87 Lower levels of vitamins C and E are related to higher levels of oxidative stress, which in turn, may lead to increased viral replication, therefore increasing viral load.92 Multivitamin supplements with vitamin C and E delay the progression of HIV by increasing CD4 and CD8 cell counts while lowering viral load.92'93
The role of vitamin D is not well studied in HIV progression, although there have been few studies regarding vitamin D status and maternal-infant morbidity and mortality, as well as vitamin D association and mother-to-child HIV-1 transmission.87 One study found that children bom to mothers with low vitamin D levels had a 64% greater risk of dying during follow-up and an overall 46% greater risk of contracting HIV.94 Conversely, in another study with a trial of 367 tuberculosis patients containing a subgroup of 135 HIV-positive patients located in Guinea-Bissau, the impact of vitamin D supplementation every four months over a twelve-month period on mortality and the clinical severity of tuberculosis was tested.95 The study found that vitamin D did not appear to have an impact on mortality in both the complete group and the HIV-positive subgroup.95 There is limited, or insufficient evidence to recommended vitamin D use among people living with HIV unless already deficient.
Selenium has been suggested to be a key nutrient for people living with HIV. Lower serum concentrations of selenium in both adults and children infected with HIV have been linked to increased viral load, and mortality.96 The role of selenium in immunity and antioxidant
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defense may be the underlying mechanism of an increased HIV progression with lower serum levels.97 Observational findings prompted various clinical trials that assessed whether selenium supplementation could have an impact on HIV viral load, CD4 counts, or HIV progression.
In a randomized control study with 186 HIV-positive men and women, who were supplemented with 200 p.g of selenium, found that the selenium did not affect CD4 count levels or viral load after two years follow-up.98 Although, a smaller proportion (25%) among the selenium group experienced a substantial decline in CD4 count, when compared to the placebo group (46%).98 Additionally, the relative risk of being admitted to a hospital was 2.4-times lower among the selenium supplemented group compared to the placebo group.98 In a randomized control trial, 262 HIV-infected patients were supplemented for nine-months with 200 p.g of selenium.99 This resulted in an increase in CD4 counts, and a decrease in viral load."
Specifically looking at the impact of selenium supplementation on HIV-positive mother and child mortality, a randomized controlled study was conducted with 913 pregnant HIVpositive women in Tanzania.100 Daily 200 p.g selenium supplementation until six months postpartum did not affect CD4 count, viral load, or overall maternal and infant mortality.100 However, six weeks after delivery, a reduction of 57% morbidity and mortality in the selenium supplemental child population was found.100 Although selenium is important for maternal and child health, overall, there is not enough evidence to support providing selenium supplements to HIV-positive persons who are not deficient, or are already receiving a high-dose multivitamin.87
In contrast, excessive supplementation of vitamin A, iron, and zinc have been associated with adverse health effects and caution is warranted for their use in HIV-positive maternal populaitons.87 Vitamin A plays an important role in immune function, and is essential for maternal and infant health. According to the WHO, supplementation of vitamin A and/or |3-
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carotene to HIV-positive women during pregnancy may reduce the risk of mother-to-child transmission of HIV.101 However, various studies have challenged that claim, and in contrast prove an increase of viral load in breastmilk with high dose supplementation of vitamin A and/or (3-carotene, therefore increasing risk of mother-to-child HIV-1 transmission via breastfeeding.
According to a Randomized Trial of Vitamin Supplements in Relation to Vertical Transmission of HIV-1 in Tanzania, a total of 1,078 HIV-positive women were given either vitamin A and (3-carotene, or a multivitamin excluding vitamin A and (3-carotene starting at 20 weeks gestation throughout lactation.102 According to the study, vitamin A and (3-carotene increased the risk of vertical HIV-1 transmission while the multivitamin excluding vitamin A and (3-carotene had no effect on the total risk of transmission.102
In the study, Effect of Vitamin Supplements on HIV Shedding in Breast Milk, 594 Tanzanian HIV-infected women received either a multivitamin, vitamin A and (3-carotene, a multivitamin including vitamin A and (3-carotene, or a placebo.103 Women received these supplements in a 2 x 2 factorial fashion during pregnancy and throughout the first two years postpartum.103 Results concluded that vitamin A and (3-carotene increased viral load in breastmilk, thus increasing risk of transmission.103
In some instances, supplementation of vitamin A and/or (3-carotene for HIV-positive women who are breastfeeding may carry additional risks, therefore contributing to mother-to-child HIV-1 transmission via breastfeeding. According to the article, Vitamin Supplementation Increases Risk of Subclinical Mastitis in HIV-Infected Women, 674 women produced 1,642 breastmilk samples for analysis of Na:K (sodium: potassium) ratio to determine risk of subclinical mastitis.104 Women were placed on a multivitamin excluding vitamin A or 13-carotene, a multivitamin including vitamin A and (3-carotene, only vitamin A and (3-carotene, or
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a placebo with breastmilk sampling every three months.104 Results found that supplementation of vitamin A and fl-carotene increased the risk of severe subclinical mastitis by 45%.104 The increased risk of subclinical mastitis directly correlates to an increase in mother-to-child HIV-1 transmission via breastfeeding.
The literature regarding vitamin A supplementation and mother-to-child HIV-1 transmission via breastfeeding is largely in need of more research. Additional research will strive to determine whether or not mothers who are HIV-positive and breastfeeding should be supplemented with vitamin A and/or fl-carotene, at what times during pregnancy and/or lactation and at what regimens. Overall, women who are deficient regarding general micronutrient status might reduce transmission rates via breastfeeding if placed on a multivitamin in order to replete and maintain appropriate nutrition status, but it may not be appropriate to megadose with vitamin A and/or fl-carotene.
Iron deficiency is the most common nutritional deficiency in the world, while the majority of people suffering are women.17 In the HIV/AIDS population, anemia is prevalent and is associated with increased mortality, HIV progression and a more rapid (50%) decline in CD4 counts leading to an early AIDS-related death.105
However, iron deficiency anemia does not increase risk of vertical HIV-1 transmission via breastfeeding. In the study, Postnatal Anemia and Iron Deficiency in HIV-Infected Women and the Health and Survival of Their Children, maternal anemia was not significantly associated with an increased risk of mother-to-child HIV-1 infection postnatally.106 Although, it has been documented that very low maternal iron stores contribute to diminished child health and survival by reducing infant iron stores, and impairing cellular immunity during breastfeeding.106107
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Proper screening for low iron stores and iron deficiency anemia in women, particularly in the HIV-positive population, will increase survival rates considerably.
Zinc deficiency amongst people living with HIV may account for an improper maturation of CD4 cells mediated through low levels of the zinc-dependent hormone, thymuline. This may lead to a less effective immune response and a higher susceptibility to opportunistic infections further perpetuating HIV to AIDS while increasing risk of morbidity and mortality.108 Several studies have been conducted with zinc supplementation to HIV-positive populations and may be harmful, rather than helpful.
In reference to, Trial of Zinc Supplements in Relation to Pregnancy Outcomes, Hematologic Indicators and T Cell Counts Among HIV-1-Infected Women in Tanzania, 400 HIV-positive women in Tanzania were assigned to receive a daily oral dose of 25mg of zinc or a placebo starting between 12 and 27 weeks gestation.109 The study found that zinc had no effect on CD4, CD8, or CD3 counts during the follow-up period, but had negative effects on hemoglobin concentrations.109
In a similar study, Zinc Supplementation to HIV-1-InfectedPregnant Women: Effects on Maternal Anthropometry, Viral Load, and Early Mother-to-Child Transmission, 400 HIVpositive pregnant women who had never been treated with antiretroviral therapy drugs received a multivitamin (vitamins B, C, E, and folic acid).110 The women were randomized to receive, in addition, either a placebo or a 25 mg daily dosage of zinc until 6 weeks after delivery.110 Results of the study showed no differences in HIV transmission, CD4 or CD8 counts, and viral load. However, zinc supplementation was inversely associated with hemoglobin levels, and was then related to a threefold increase in the probability of maternal wasting.110
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Further research is warranted to assess whether there is a potential role for zinc supplementation among HIV-positive persons treated with antiretroviral therapy drugs, and those who have never been on treatment. However, it may not be appropriate for pregnant HIVpositive women to be supplemented with zinc, as it may lead to increased wasting.
Overall, HIV-positive women who are deficient regarding general micronutrient status may reduce transmission rates via breastfeeding if placed on a multivitamin regimen in order to replete and maintain appropriate nutrition status. However, it may not be appropriate to megadose with vitamin A, and/or (I-carotene, zinc or iron. Without proper access to health care and breastfeeding education, women are likely to transmit HIV to their infants when comorbidities arise and if supplementation is not appropriate. Maternal health status can greatly influence rates of increased or decreased HIV-1 transmission via breastfeeding.
Global Health Policy
I. Developing Nations
Health policy differs at the local, national and global level. With differing circumstances across the world, global health policy is crafted and determined by issues which affect communities and the majority of at risk populations. HIV/AIDS has existed for years, dating back to the 1950s, later reaching the United States in the mid-to late 1970s.111 In 1983, scientists discovered the virus that causes HIV and AIDS, only thirty-four years ago.111 HIV/AIDS is a relatively new disease which has infected and killed millions. Various policies at the national and global level have been established and revised aimed at thwarting and reducing the instance of HIV/AIDS.
Once researchers and scientists discovered that HIV can be transmitted vertically, programs have been implemented to prevent mother-to-child HIV-1 transmission. Although,
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there is no single means of prevention, therefore, global and national organizations have changed recommendations and policies repeatedly over the last thirty years.
When recommendations and policy are revised, new research and information alters current recommendations providing more culturally appropriate and evidence-based material. Various topics can change recommendation and policy which may include challenges with implementation, as well as coverage and quality of interventions being disturbingly low and inaccurate.112 Furthermore, insufficient or non-existent infant feeding counseling provided by health workers leads to inappropriate feeding choices by both HIV-infected and HIV-uninfected women.112 Poor counseling recommendations on breastfeeding consequently cause sharp increases of infant death from diarrheal episodes and pneumonia.112 Therefore, problematic issues have to be considered in order to provide recommendations that are evidence-based and appropriate for the at risk population.
Most notably, the World Health Organization (WHO) has been releasing and reviewing recommendations for HIV-positive mothers since 2000 aimed at decreasing and preventing vertical HIV-1 transmission. However, the WHOs recommendations have drastically changed over the last 17 years.
In 2006 the WHO recommended exclusive breastfeeding for HIV-infected women for the first 6 months of life unless replacement feeding was acceptable, feasible, affordable, sustainable, and safe for them and their infants before that time.112 Additionally, when replacement feeding was acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected women was recommended.112 Additionally, the 2006 WHO guidelines recommended lifelong antiretroviral therapy drugs for pregnant women, based on specific eligibility criteria. Lifelong antiretroviral therapy could be started for pregnant women
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who had a CD4 count below 200 cells/mm3, which is generally the stage of the disease in which the immune system is no longer able to effectively prevent opportunistic infections.112 Among the guidelines and recommendations for HIV-positive breastfeeding, programmatic implications for monitoring and evaluation, as well as implications for conflict and emergency settings also exist.
In 2010, recommendations from the WHO changed again stating that women known to be HIV-infected (and whose infants were HIV-uninfected or of unknown HIV status) should exclusively breastfeed their infants for the first 6 months of life, introducing appropriate complementary food thereafter, and continue breastfeeding for the first 2 years of life.113 The WHO 2010 recommendations also provided national governments the option of recommending either (1) exclusive breastfeeding and antiretroviral therapy drugs for women who meet eligibility criteria, or (2) recommend avoidance of all breastfeeding, which would most likely give the infant a greater change of HIV-free survival.113
The 2010 WHO guidelines promote starting lifelong antiretroviral therapy drugs for all HIV-positive pregnant women with severe or advanced clinical disease (stage 3 or 4), or with a CD4 count at or below 350 cells/mm3, regardless of symptoms.113 As soon as the eligibility criteria are met for pregnant and non-pregnant HIV-positive women, antiretroviral therapy drugs could be initiated.113
In 2015, WHO recommendations changed once more. Currently, HIV-positive mothers should breastfeed for at least 12 months and may continue breastfeeding for up to 24 months or longer while being fully supported for antiretroviral therapy drug adherence.114 The next time the WHO guidelines and recommendations regarding prevention of mother-to-child HIV-1 transmission will be updated is in 2019.114 Countries are encouraged to hold discussions to
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inform decision-making on the use and introduction of the 2015 WHO recommendations into national programs.114
For the first time, current WHO guidelines recommend two interventions involving antiretroviral therapy drugs: (1) providing lifelong antiretroviral therapy drugs to all pregnant and breastfeeding women living with HIV, regardless of CD4 count or clinical stage, and (2) providing antiretroviral therapy drugs for HIV-positive pregnant and breastfeeding women during the mother-to-child transmission risk period, and then continuing lifelong antiretroviral therapy drugs for those women eligible for treatment for their own health.115 This allows the child to benefit from breastfeeding with little risk of becoming infected with HIV. However, attaining and compliance of taking the recommended antiretroviral therapy drugs may not be as simple as the current recommendation suggests. The combination of exclusive breastfeeding and antiretroviral therapy drugs can significantly reduce the risk of vertical HIV-1 transmission via breastfeeding.14
The WHO-led Kesho Bora study found that giving HIV-positive mothers a combination of antiretroviral therapy during pregnancy, delivery and breastfeeding reduced the risk of HIV transmission to infants by 42%.14 The breastfeeding Antiretroviral and Nutrition study in Malawi also showed a risk of HIV transmission reduced to just 1.8% for infants given the antiretroviral drug Nevirapine daily while breastfeeding for six months.14
A simple method of trying to reduce transmission rates of HIV through breastfeeding would be to offer free infant formula to the HIV-positive maternal population. Although, distribution of free infant formula seems to encourage mixed breastfeeding, consequently increasing rates of HIV transmission and infant death.84 The greatest declines in breastfeeding
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have taken place in countries where infant formula has been distributed at no cost, South Africa being a prime example.
In the early 2000s, South Africa had some of the highest rates of HIV prevalence in the world. In 2001, in order to prevent mother-to-child HIV-1 transmission, infant formula was distributed by national and local authorities in addition to local nongovernmental organizations at no cost for all infants up to 6 months of age.116 The free formula was provided at all public health facilities, although, the policy had unforeseen consequences women who were not HIV-positive turned to infant formula as well.116 This initiative inevitably undermined breastfeeding, as a result, breastfeeding rates plummeted to roughly 1.5% nationwide in 2003.116 Infant death subsequently skyrocketed, and South Africa was left with a challenging decision on how to fix the issue.
In 2011, South Africa passed the Tshwcme Declaration aimed at improving low breastfeeding rates while increasing infant survival. The policy mandates that public health facilities stop providing infant formula to all new mothers, while promoting milk banks, and increasing counseling services about the importance of breastfeeding. In 2016, exclusive breastfeeding rates for the first 3.5 months postpartum were at approximately 40%, although, rates decrease to 8% at six months.117 Significant increases in breastfeeding over the last 5 years, points to success with South Africas newest policy implementation. HIV-positive mothers are provided free antiretroviral medication, and are forced to exclusively breastfeed if they cannot afford infant formula as none will be provided free of charge. Exclusive breastfeeding, coupled with accessible antiretroviral therapy drugs, has decreased mother-to-child HIV-1 transmission, while significantly increased exclusive breastfeeding rates and decreasing infant death.
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However, the Tshwcme Declaration poses an issue for mothers who need to return to work, or leave their child in the care of someone else for whatever reason.118 Now these mothers are faced with the issue of finding alternative feeding methods for their infants or trying to express breastmilk in the workplace. Certain organizations and places of work may not be suitable for pumping or expressing breastmilk for an infant. Workplaces may also lack appropriate storage for the expressed breastmilk during work hours. Additionally, women may be commuting long hours to work and cannot store expressed breastmilk appropriately on their way back home.116
It has been documented that antiretroviral therapy drugs can drastically reduce rates of mother-to-child HIV-1 transmission. In developed countries, providing antiretroviral therapy drugs for mother and infant is standard of care decreasing mother-to-child HIV-1 transmission rates to below 2%.11 In developed countries such as the United States, breastfeeding while HIVpositive is contraindicated, even on antiretroviral therapy drugs. As said by the American Academy of Pediatrics, In the industrialized world, it is not recommended that HIV-positive mothers breastfeed.13 The position statement does take into account developing countries and HIV-positive mothers breastfeeding,
However, in the developing world, where mortality is increased in non-breastfeeding infants from a combination of malnutrition and infectious diseases, breastfeeding may outweigh the risk of the acquiring HIV infection from human milk Infants in areas with endemic HIV who are exclusively breastfed for the first 3 months are at a lower risk of acquiring HIV infection than are those who received a mixed diet of human milk and other foods and/or commercial infant formula Recent studies document that
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combining exclusive breastfeeding for 6 months with 6 months of antiretroviral therapy significantly decreases the postnatal acquisition of HIV-1.13 The American Academy of Pediatrics also states,
. continued ingestion of illicit drugs or alcohol, and underlying conditions, such as HIV infection, are not compatible with breastfeeding. Patients also require ongoing psychosocial support to maintain abstinence.13
The CDC has a much more declarative stance on the issue, It is not advised to breastfeed if the infants mother has been infected with HIV, or is taking antiretroviral medication.121 Although the WHO has provided suitable guidelines for HIV-positive breastfeeding for women of developing countries, in developed countries, such as the United States, policy differs.
The American Academy of Pediatrics takes into account women of developing countries, however, they do not denote anything about cultural stigmatization, cultural barriers, or superstition issues that are prominent many cultures and countries. When women of developing countries seek asylum, immigrate, or become refugees in the United States, the question of whether or not HIV-positive women are receiving care based on policy alone or in conjunction with cultural health beliefs develops.
From 1993 until January, 2010 positive HIV status was considered a ground of inadmissibility in the United States. HIV-positive foreign nationals would be denied short-term visas or applications for lawful permanent residence based solely on HIV status.120 Various countries worldwide have similar, strict, regulations on entry, stay and residence for people living with HIV. Countries that currently have an entry ban for people living with HIV/AIDS are as follows: Brunei, Equatorial Guinea, Iran, Iraq, Jordan, Papua New Guinea, Qatar, Russia, Singapore, Solomon Islands, Sudan, the United Arab Emirates, and Yemen.121 Countries that
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have travel and residence bans in the context of positive HIV/AIDS status have considerably smaller prevalence of people living with HIV/AIDS, compared to many other parts of the world.122
After a twenty-year HIV travel and immigration ban in the United States, on January 4, 2010 it came to an end. Being HIV-positive is no longer an automatic ground of inadmissiblity.120 Doctors no longer perform an HIV assay as part of the medical examination, although, the doctor could ask questions about overall health in which HIV status could come up. When The Department of Health and Human Services (HHS) final regulations went into effect, it removed HIV from a list of communicable diseases of public health significance. Although, some doctors may continue to use the old form, they are now instructed not to test for HIV.120
Many women and children seek asylum and/or refugee in the United States because of the stigmas and hardships associated with positive HIV status in their own country. During 2007-2008, approximately 14% of the incoming refugees to the United States arrived from countries with HIV prevalence >5%.123 Since the 2010 ban on travel restrictions for persons living with HIV, assumptions can be made that a significant increase of HIV-positive people have, and are, immigrating and seeking refugee status in the United States annually. The CDC outlines postarrival screening methods in order to best serve the health of people living with HIV who are moving to the United States.123
Current CDC guidelines for the United States recommends HIV screenings in health-care settings for all refugees aged 13-64, not to deny entry, but as a preventative measure.123 For refugees who may be considered in the window period when they arrive, repeat screening 3-6 months following resettlement is recommended.123 The window period of HIV varies from person to person. Most HIV tests are antibody tests, although, the body takes time to produce
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enough antibodies for an HIV test to detect the disease.124 The soonest an antibody test will
detect infection is at three weeks post infection.124 However, most people will develop detectable
antibodies closer to 4-12 weeks post infection.
124
' v X X/x X x :xx yx *: x x x X
X x xX ***x$***J x
x x :xxxxVxx**: It
Wesk 2
Week 3
Week 4
Week 12
Infection
Time from infection (weeks)
Each 'x' represents the time when a different person develops HIV antibodies. Testing is only useful when the majority of infections would be detected. Testing after 2 or 3 weeks is not very useful.
Source: http://i-base.info/guides/testing/what-is-the-window-period
The CDC guidelines have special pediatric considerations regarding HIV and testing. Children <13 years of age should be screened unless the mother of the child can confirm HIVnegative status. In most situations, complete risk information will not be available, therefore, most children <13 years of age should be screened.123 Children who are <18 months of age who initially test positive for HIV antibodies, should receive further testing with DNA or RNA assays. Results of an initial positive antibody test in this age group can be unreliable, as they may detect persistent maternal antibodies.123 Additionally, all children born to, or breastfed by an HIV-positive mother should receive antiretroviral therapy beginning >6 weeks of age until confirmed to be uninfected.123
In the pregnant refugee population, all women should undergo routine HIV screening as part of their post-arrival and prenatal medical screening and care.123 During initial intake assessments, disclosure of HIV status may not be forthcoming. It is imperative that the screening and assessments in this population is done with dignity, and in a supportive manner. Refugees represent a population vulnerable to HIV infection and disease, therefore HIV screening should
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be offered to all refugees, immigrants, and persons seeking asylum resettling in the United States.123
Overall, global and national health policy are ever changing. Health policy can be seen as an umbrella, covering most, but not all. Although health policy aids the majority in need, some policies may not be appropriate for certain populations. With an increase in research, and continued information in the context of vertical HIV-1 transmission, policy will constantly change until the epidemic is reduced. With global health policy shifts, compliance with recommendations and policy is passive. Global health policy then becomes essentially ineffective in populations who need it most.
II. Compliance with Global Health Policy
Policy shifts can impact people at all levels. The ultimate goal of global health policy is to provide evidenced-based recommendations to the HIV-positive maternal-infant dyad, while taking into consideration cultural differences, and barriers. Global health policy is obligated to promote recommendations enabling maternal and infant health. However, it is difficult to provide recommendations on a global level when research on the subject is still being done. HIV/AIDS is such a new disease, that recommendations over the last twenty years have changed dramatically attempting to prevent and reduce mother-to-child HIV-1 transmission.
Recommendation shifts from the WHO negatively impact HIV-positive mothers who have to make the difficult decision to either initiate or avoid breastfeeding, as well as the health workers counseling and proving advice to this population. These various global health policy shifts are confusing health workers and HIV-positive mothers, to a degree that policy becomes relatively ineffective, and complicates prevention programs.
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Many countries continue to face shortages of trained health workers.125 Additionally, the effectiveness and efficiency of available personnel is lacking.125 There are challenges concerning health workers to keeping prevention programs ongoing and successful. Effective programs require more than basic resources, therefore, proper training is dynamic and difficult.126 Health workers may not have up-to-date information and recommendations in the context of vertical HIV-1 transmission via breastfeeding.126 It is thought that health workers need contextualized, easy-to-follow guidelines in order to effectively provide evidence-based advice and services.126 Supportive supervision should also be in place to enable health workers to provide a confident service.
Program managers, counselors and HIV-positive pregnant women continue to be confused with shifting global health policy and recommendations. Low levels of knowledge and awareness pertaining to infant feeding options confirms a need for clarity.127 Many counselors and health workers either avoid the topic during counselling sessions, or push women in a particular direction, that may not be suitable at an individual level.127 As a result, HIV-positive women are given inadequate knowledge to make appropriate infant feeding choices.127
The social and cultural distance between the producers of the guidelines and the global recipients has generated a sense of helplessness, confusion, guilt and fear among people involved in interventions within certain populations.128 HIV-positive women have been unable to adhere to the changing infant feeding recommendations without emotional stress and fear of harming their infant.128 Counselors have reported uncertainty and loss of faith with their work in infant feeding after experiences with large numbers of non-compliant HIV-positive mothers.128 Overall, many health workers are worried that the continual confusion regarding infant feeding has reduced public trust in nursing as a profession.128
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The lack of clarity with shifting global health policy promotes mixed feeding methods as confusion rises. HIV-positive mothers may be recommended to feed their infant in a certain way from health workers who are not as knowledgeable about the topic as they should be, or health workers may be referencing old recommendations, or something false they have heard from a program manager. Confusion increases in both the counselor and HIV-positive mother, which contributes to psychological barriers, as well as inappropriate infant feeding methods.
Following the release of the 2015 WHO guidelines, the global organization no longer recommends multiple options for prevention of mother-to-child HIV-1 transmission, but instead advises that all HIV-positive pregnant and breastfeeding women should receive antiretroviral therapy drugs regardless of clinical stage (CD4 count) of disease provided by national governments. This approach has since been adopted by most countries with high burden of disease.129 However, there are numerous issues with implementing this method to reduce and prevent mother-to-child HIV-1 transmission. Common antiretroviral therapy drugs for the HIVpositive maternal-infant dyad include: Zidovudine (retovir), and Nevirapine (viramune).130
With use of Zidovudine, serious side effects can arise. Severe bone marrow problems have been reported, especially in patients with advanced HIV infection causing anemia. Additionally, instances of lactic acidosis, as well as severe and sometimes fatal liver problems have also been reported.131 Iron deficiency anemia is the most common deficiency worldwide, and prevalent in the HIV-positive female population.17 Lifetime use of Zidovudine will perpetuate the high rate of anemia in HIV-positive women causing increased comorbidities, greater risk of opportunistic infection and subsequently death. Additionally, 51.4% of people taking this drug experience nausea, 21.1% anorexia, and 17.2% vomiting.131
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Severe side effects have been reported with the use of Nevirapine as well. Fatal liver problems have occurred in patients, especially during the first 18 weeks of therapy, but may occur at any time during treatment.132 Pregnant women, and women with a CD4 count higher than 250mm3 are at greatest risk. Major and common side effects of Nevirapine include: diarrhea, nausea, and vomiting, plus sores, ulcers, or white spots in the mouth or on the lips.131 Up to 10% of people on Nevirapine experience nausea and vomiting, and up to 5% experience diarrhea.132
Almost 52% of people who take Zidovudine experience nausea, while 20% of people experience vomiting.131'132 Additionally, 10% of people taking Nevirapine experience vomiting, with 10% experiencing diarrhea.133'134 The combination of taking both drugs increases nausea and diarrhea which can in turn decrease therapeutic levels of the antiretroviral therapy drugs. Sub-therapeutic drug levels cause decreased medication effectiveness that impairs the efficiency of the drugs leading to instances of vertical HIV-1 transmission via breastfeeding even while taking the prescribed medication.133 Additionally, side effects with medication were the most commonly reported barriers to antiretroviral therapy drug adherence.30
As the disease progresses into the symptomatic stage of HIV, common symptoms increase and become more prominent. Notable issues relating to untreated HIV progression, are the instances of chronic diarrhea, weight loss, in addition to mouth and skin problems.134 The 2015 WHO recommendations suggest providing antiretroviral therapy drugs at no cost to HIVpositive mothers without eligibility requirements. If an HIV-positive pregnant women is already in the third stage of HIV, chronic diarrhea is prominent, and antiretroviral therapy drugs would perpetuate that issue which could decrease therapeutic levels of the drugs provided. '
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Assumptions can be made that a majority of HIV-positive pregnant women are also drinking unclean water thereby increasing risk of diarrheal episodes from waterborne pathogens. Therapeutic levels of antiretroviral therapy drugs are reduced with instances of diarrheal episodes from unclean water, disease progression, and side effects of antiretroviral therapy drugs.135 In order to increase sub-therapeutic levels to effective ranges, additional antiretroviral medication is warranted and blood serum levels should be tested frequently. The above limitations will test the sustainability of recommended antiretroviral therapy drugs for all HIVpositive women in upcoming years.
Although there are downsides to taking antiretroviral therapy drugs, in the context of saving lives, they are essential. Since 1995, an estimated 1.6 million new HIV infections among children have been averted due to the provision of antiretroviral medication.77 Antiretroviral therapy drugs do not cure HIV or AIDS, but the disease is treated using a combination of medications aimed at suppressing the amount of the HIV virus in the body.136 Antiretroviral therapy drugs prevent HIV from multiplying while giving your body a chance to recover and fight off infections and cancers caused by the disease.136 Additionally, the use of antiretroviral therapy dugs decrease risk of transmitting HIV to others as well as prolong life expectancy of the infected individual.136
In 2005, only seven developing countries provided free antiretroviral therapy drugs to at risk populations: Botswana, Brazil, Ethiopia, The United Republic of Tanzania, Thailand, Senegal and Zambia.30 The countries decided to abolish user fees for HIV treatment in order to increase adherence and overall public health.30 The importance of no cost treatment is significant because cost of any amount prevents people from adhering to antiretroviral therapy.30 Throughout the years, as access to antiretroviral therapy drugs increased, many populations were
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able to effectively utilize health care services to prolong their lives and reduce risk of transmission. However, because of prominent barriers, only about half of women who were eligible for antiretroviral therapy drugs were accessing treatment.137
When the WHO put out the 2015 recommendations concerning prevention of mother-to-child HIV-1 transmission and antiretroviral therapy, treatment priorities included: increasing the demand for antiretroviral therapy, investment in antiretroviral therapy programs, and effective delivery of antiretroviral therapy services.30 African governments are among leaders in global efforts to mobilize resources for antiretroviral therapy; domestic contributions account for roughly half of all spending on HIV treatment and care across sub-Saharan Africa.138 Notable countries including Botswana, Angola and South Africa finance 80% of antiretroviral therapy drugs through public and private sources.138 Several countries have been exploring innovative financial strategies in order to diversify funding and generate renewable sources of funding for HIV programs.138 As an example, in Cote dIvoire, tobacco and alcohol are being taxed to generate funds for HIV and AIDS response.138
National priorities for HIV spending is important for the effectiveness of HIV response. The magnitude of costs is a serious challenge for many countries, 83% of domestic financing goes to care and treatment in sub-Saharan Africa. South Africa alone distributes a sizable amount of antiretroviral therapy drugs, owing to increased prevalence of the disease.138
Although there is significant financial support from domestic contributions, external donors (The United States, and other developed countries) supplement HIV prevention programs which include antiretroviral therapy drugs.31138 The cost of antiretroviral therapy drugs for all persons infected with HIV is grossly high, which remains concerning for sustainability efforts for financing HIV/AIDS care and treatment.138
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The United States alone has provided funding to address the global HIV epidemic starting in 1986.139 Total funding has increased since initiation, although, since about 2010, funding from the United States has remained relatively flat.139 Of the $6.6 billion (USD) spent each year on global HIV/AIDS efforts by the United States, $5.2 billion (USD) is allocated to bilateral programs, and $1.35 billion (USD) is distributed as a U.S. contribution to The Global Fund to Reduce AIDS, Tuberculosis and Malaria.139
Table 1: Federal Funding for HIV/AIDS by Category, FY 2011 FY 2017 Request (US$ Billions)
Category FY 2011 FY 2012 FY20lf FY 2014 FY201S FY2016 FY 2017 Request
Domestic $21.8 $22.0 $22.5 $23.9 $25.5 $26.4 $27.5
Care $15.3 $15.5 $16.1 $17.4 $18.9 $19.7 $20.8
Cash/Housing $2.7 $2.8 $2.9 $3.0 $3.0 $3.0 $3.1
Prevention $0.9 $1.0 $0.9 $0.9 $0.9 $0.9 $0.9
Research $2.8 $2.8 $2.7 $2.7 $2.7 $2.7 $2.7
Global $6.5 $6.4 $6.3 $6.6 $6.6 $6.6 $6.6
TOTAL $283 $28.5 $28.8 $30.5 $32.1 $33.0 $34.0
NOTES: (a) indicates FY 2013 includes the effects of sequestration.
Source: The Henry J. Kaiser Family Foundation. Global health policy: U.S. federal funding for HIV/AIDS: trends over time. Updated 2016. http://kff.org/global-health-policv/fact-sheet/u-s-federal-fuiiding-for-hivaids-trends-over-time/. Accessed April 30.2017.
Currently, there are around 18.2 million people on treatment for HIV worldwide, 10 million of which through programs supported by The Global Fund.140 In 2015, $33 billion (USD) in cumulative and fully paid contributions from various donors and governments was allocated by The Global Fund to support programs based on national health strategies, and to operate in a balanced manner within different regions for HIV, Tuberculosis and Malaria.140 Overall costs are expected to increase with the 2015 WHO recommendations and policy that delineates lifelong antiretroviral therapy drugs provided at no cost to HIV-positive pregnant women without eligibility requirements. Indicated below, an increase of 6.9 million people are now eligible for antiretroviral therapy drugs, therefore, there will be increased costs associated.
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ART eligibility: 5 policy scenarios
Estimated millions of people eligible for ART (2014)
30 m. 36.9 mT
^ o CD4 < 200 r o CD4 < 350 ' CD4< 350 + TasP r 4 !|
Recommended since 2003 J Recommended since 2010 J Incremental approach 2012 + indications for ART at any CD4 Treat ALL
2013 guidelines 2015 guidelines
8 I
icouver Saturday 18July2015
World Health Organization
Source: Doherty M. New directions in the 2015 WHO Consolidated ARV Guidelines. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), Vancouver, Canada. 2015.
National and global organizations need to find sustainable resources in order to
implement the new WHO recommendations with future success. Furthermore, HIV-positive
women may have additional barriers to attaining and complying with antiretroviral therapy drug
regimens. Although antiretroviral therapy drugs have become available to the at risk population
in many developing counties, several governments and health clinics still have not adhered to the
current WHO recommendations and policy guidelines. For many HIV-positive women of low
socioeconomic status, health clinics are far out of reach not only because of transportation barriers.141 Owing to the prominent and negative stigmas associated with HIV-positive status,
many women will often travel to different towns altogether in order to receive treatment or pick
up appropriate medication for fear of being ostracized from their homes and communities by visiting the nearest health clinic.142
The perpetual shifts in global health policy and recommendations, in addition to non-
adherence poses difficulties in thwarting mother-to-child HIV-1 transmission on a global scale.
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With the WHOs recommendations, and revisions of recommendations, health workers and HIVpositive mothers become confused and proper information is not relayed therefore perpetuating mother-to-child HIV-1 transmission via breastfeeding. Without proper knowledge of current and evidenced-based recommendations, negative effects can occur.
Conclusion
In the Unites States and other developed countries, medical advancements have allowed a less than 2% risk of mother-to-child HIV-1 transmission.11 Per policy and position statements from the American Academy of Pediatrics and The Centers for Disease Control and Prevention, breastfeeding is contraindicated by HIV-infectivity.13,120 With maternal and infant antiretroviral medication, elective caesarian sections (C-section), and safe alternative methods to infant feeding, people in developed countries pose relatively no risk of mother-to-child HIV-1 transmission.25'26 However, the complex issues surrounding vertical HIV-1 transmission in developing countries is still prominent today.
In 2015, if a person was diagnosed with HIV in one of 13 countries including: Argentina, Australia, Brazil, the United Kingdom, France, the Maldives, Mexico, the Nederlands, Spain, South Korea, Thailand, Turkey and the United States, policies mandated that any person with HIV have access to treatment, regardless of CD4 count (stage of HIV progression).143 In contrast, any other country in the world had policies that prolonged appropriate treatment until eligibility requirements regarding CD4 count were met.143
Scientific evidence strongly supports immediate access to HIV treatment as it improves the health of people living with HIV, and is one of the most effective tools in decreasing transmission rates.136 Up until 2015, most people living with HIV/AIDS in developing countries
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had to be sick, or at much greater risk of future illness and premature death, before they could get the treatment that prolongs health while virtually eliminating risk of transmission to others.143
There have been accomplishments and hindrances with various different global health policies and recommendations in the context of mother-to-child HIV-1 transmission in developing countries. Throughout the years, global health recommendations and policies have shifted with increased research and knowledge surrounding the relatively new disease. This shifting has caused significant confusion for health workers providing advice to HIV-positive mothers who have to make the challenging decision of whether or not breastfeeding is best for them and their child. A single global health policy and recommendation is warranted to aid in evidence-based prevention of mother-to-child HIV-1 transmission via breastfeeding.
The current policy in South Africa eliminates the use of infant formula within low socioeconomic populations which has drastically increased exclusive breastfeeding rates while decreasing infant morbidity and mortality. Implementing this policy to all endemic HIV/AIDS countries will provide the best chance at survival for infants and mothers alike. South Africas current policy and recommendations coupled with the WHOs current 2015 policy providing lifelong antiretroviral therapy drugs to all HIV-infected mothers will reduce mother-to-child HIV-1 transmission while prolonging the life of mother and infant.
This idea is not perfect. If this policy were implemented globally, many HIV-positive mothers would be disadvantaged. Many mothers would have to return to work, or discontinue breastfeeding for other reasons. Some mothers may not seek out antiretroviral therapy drugs attributed to stigma association. Yes, children will become infected with HIV, and many will die, but South Africas current recommendations will be the most effective method to reduce and prevent vertical HIV-1 transmission via breastfeeding in other developing countries. With shifts
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in global health policy and recommendations causing confusion and doubt, one policy and recommendation needs to hold true in order to enable health workers with the skills to empower HIV-positive mothers to seek now available treatment, while promoting maternal and infant health above all else.
In an ideal situation, policy would require places of work to provide safe and appropriate spaces for breastfeeding with adequate storage, in addition to appropriate time to express. Furthermore, health workers would always be up-to-date on current recommendations and evidenced-based care from proper training. There would be no stigma associated to HIV infectivity, and all HIV-positive mothers would effortlessly adhere to antiretroviral therapy drug treatment. This is obviously not realistic, but efforts could be made.
Through the course of the HIV/AIDS epidemic many accomplishments have been made with efforts to prevent mother-to-child HIV-1 transmission, most notably, by providing antiretroviral therapy drugs at no cost to HIV-positive mothers. The recent 2015 WHO guidelines recommend that all pregnant HIV-positive women be started on antiretroviral therapy drug treatment regardless of disease stage which enables women to receive the medication they need to reduce transmission rates, while improving their own health. The previous come back when youre more sick policies are fortunately changing.
The WHO estimates that >95% of pregnant women in South Africa living with HIV (257,456 people) received antiretroviral therapy drugs aimed at preventing mother-to-child HIV-1 transmission.33 In South Africa 53% of HIV-positive women are currently on antiretroviral therapy drugs.144 However, of the 4 million HIV-positive women in South Africa aged 15 years and older, only 6.7% are currently on antiretroviral medication in 2016.32 Assumptions can be made that more than 6.7% of the HIV-infected population of South Africa is reproducing, which
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is why many other women are on treatment, although, it is only about half of the female population. The above data is primarily collected from antenatal clinics. Therefore, assumptions can be made that a disproportionate number of HIV-positive pregnant women are not accessing preventative care.
Asking women to seek antiretroviral medication when they become pregnant regardless of clinical stage of HIV is a human rights accomplishment. Although, this preventative measure can be improved. In order to truly prevent HIV-1 transmission rates, not only in the context of mother-to-child HIV-1 transmission, antiretroviral medications should be provided to all women, and truly all HIV-infected people. As of June 2015 the Joint United Nations Programme on HIV and AIDS estimates that 18.2 million people globally were accessing antiretroviral therapy, only 49% of the HIV infected population.145 In contrast to South Africa, only about 77% of all HIVpositive women globally had access to antiretroviral therapy treatment aimed at preventing HIV-1 transmission from mother-to-child.145 Without access to effective treatment and health services, people are left to illness and death, the rate of new infections will continue to increase.
With the 2015 WHO recommendations, health workers in developing countries need to be trained to empower HIV-positive soon-to-be, and current mothers to actively seek out antiretroviral therapy drugs to improve their health, while decreasing risk of transmission. In order to truly impact prevention, antiretroviral medications should be distributed at no cost to all women who are HIV-positive-53% of the HIV population accessing treatment is not good enough. Additionally, one policy in endemic countries should be mandated providing recommendations for breastfeeding while HIV-positive.
South Africa alone spent roughly $1.5 billion USD on its HIV/AIDS programs in 2014.146 With South Africas new commitment to funding lifelong antiretroviral therapy drugs,
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the sustainability of domestic funding will become challenging in the upcoming years.146 With help from external donors and international government financial support, funds for all countries affected by the HIV/AIDS epidemic could be manageable. Financial support would provide the standard of care good enough for HIV-infected populations in developed countries, but only recently good enough for HIV-infected populations living in developing countries. With the current medical knowledge and pharmaceutical drugs, coupled with increased evidenced-based knowledge provided to people working on the front lines, in theory, the HIV/AIDS epidemic could be reduced to almost nothing in one single generation.
At the end of 2015, $19 billion USD was invested in AIDS response programs throughout developing countries, with 57% of funding from domestic resources.143 In 2020, estimates indicate $26.2 billion USD will be required for the AIDS response, and $23.9 billion USD in 2030.146 However, the global economy will pay more for the response to the epidemic in the long run. Paying up and treating people now, saves money later. Mother-to-child HIV-1 transmission and the HIV/AIDS epidemic as a whole is a multifaceted issue, there is no single way to fix the problem. The above recommendations regarding increased funding and access to antiretroviral therapy drugs, coupled with implementing a single recommendation and policy in the context of infant feeding and HIV-infectivity, while empowering HIV-positive mothers to access treatment may not be realistic, but why not try.
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Nutritional Implications of Vertical HIV 1 Transmission via Breastfeeding in Developing Countries by Ellana Williams An undergraduate thesis submitted in partial completion of the M etropolitan State University of D enver Honors Program May 5, 2017 Dr. Bruce Rengers Dr. Melissa Masters Dr. Megan Hughes Zarzo Primary Advisor Second Reader Honors Program Director

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! Nutritional Implications of Vertical HIV 1 Transmission via Br eastfeeding in Developing Countries Metropolitan State University of Denver Ellana Williams

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES # Table of Contents Abstract 3 Acknowledgement s .. 4 Introduction ... ... 5 Issues in Developing Countries I. Benefits of Breastfeeding 10 II. Breastfeeding with HIV/AIDS 15 III. Alternative M ethods of Infant Feeding .. 18 IV. Stigma Association .... ... 3 3 V. Factors Which May Effect Vertical HIV 1 Transmission .. 39 Global Health Policy I. Developing Nations ... .. 4 7 II. Compliance with Global Health Policy ... 5 6 Conclusion ...... 6 4 References 69

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $ Abstract The HIV/AIDS epidemic has been a leading cause of death in developing nations; current d isease infectivity remains a multifaceted issue throughout endemic areas of the world Women who are HIV positive have many risks and barriers in the context of overall nutrition status, coupled with social and economic issues which pose difficult y in determining whether or not to breastfeed. The purpose of this thesis is to provide a literary analysis regarding vertical HIV 1 transmi ssion via breastfeeding in developing countries focusing on nutritional implications and global health policy. Per n utrition research and data, exclusive breastfeeding provides nutritional, immune, and long term benefits for the infant in conjunction with a variety of maternal benefits. While it has been demonstrated that breastfeeding is the gold standard method of inf ant feeding, this choice will therefore pose a controversial and difficult decision for HIV positive mothers regarding risk of mother to child HIV 1 transmission. With culturally appropriate understanding of these complex issues, determination of whether o r not women who are HIV positive should breastfeed will be discussed in correlation with dissimilar global health policy in developed vs. developing nations.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES % Acknowledgement s I would like to thank my primary thesis advisor, Dr. Bruce Rengers of the Human Nutrition and Dietetics Department at Metropolitan S t ate University of Denver for continuous support and direction throughout this endeavor Without Dr. Renger s participation and input, my Honor's thesis would not have been successfully completed. The culmination of this research has invaluably broadened my education in dietetics and i nspired me to work with the HIV positive maternal infant dyad in the near future. I would also like to thank Dr. Meghan Hughes Zarzo, Honors Di rector at Metropolitan State University of Denver for providing a platform to enhance my education f r om this challenging a n d rewarding accomplishment Her kind helpful support and encouragement throughout, has been much appreciated. I would also like to acknowledge Dr. Melissa Masters of the Human Nutrition and Dietetic s Department at Metropolitan State University of Denver as the second reader of my Honor's thesis T hank you for your invaluable discussion, ideas, and feedback. Final ly, I must express my profound gratitude to my family, peers, and Metropolitan State University of Denver 's faculty for providing me unfailing support and continuous encouragement throughout this process of researching and writing. This accomplishment woul d not have been possible without them. Thank you. Ellana Williams

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES & Introduction Exclusive breastfeeding has been demonstrated as the gold standard m ethod of infant feeding Infants who are exclusively breastfed are provided with complete nutrition for the first six months of life and additional benefits beyond the six month mark Breastmilk provides the perfect ratio of macro nutrients, with high bioavailability of micronutrients for the infant As the child grows, breastmilk 's nutritional composition ch anges for the infant s respective nutritional needs. Infants gain non nutritive properties from breastmilk as well, including maternal immune factors which function in the infant's gastrointestinal tract to actively protec t from disease. Breastfed infants have higher IQs and are less likely to acquire illnesses and other health conditions later in life as often as non breastfed babies. In developing countries, the benefits of breastfeeding stretch further. According to the Worl d Health Organization (WHO) improving brea stfeeding practices, specifically in developing countries, could prevent more than 1 million infant deaths annually. 1 Each year 8.2 million children under the age of five die, w ith 99% of deaths occurring in developing countries, particularly i n Africa and South East Asia. 2 Nearly 3.3 million child deaths under the age of five are among neonates infants in their first 28 days of life while the additional 4.9 child deaths occur between the age of 28 days and five years old 2 The two leading causes of global infant death are re spiratory infections, and diarrhea 2 B reastfeeding drastically reduces the incidence of both In developing countries, breastfeeding is a matter of life and death. Children who are not breastfed are approxima tely 56 % more likely to have prevalent diarrh ea l episodes increasing risk of death from dehydration. 3 Breastfed infants are also 47% times less likely to die of a respiratory infection such a s pneumonia which is a leading cause of child

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES morbidity and mortality 4 5 In order t o reduce the prevalence of infant death, breastfeeding is essential to sustain the lives of children particularly in developing countries. With the high est rate of infant death localized in Africa and South East Asia, breastfeedin g should be a mother's number one priority aimed at reducing infant and child death Certain extenuating circumstances and contraindications may come to light that influence a woman's decision to breastfee d like the HIV/AIDS epidemic. HIV positive mothers can transmit this disease to their children through vertical (mother to c hild) HIV 1 transmission. According to The United Nations Children's Fund ( UNICEF ) between 15% and 25% of children born to HIV infected mothers become vertically infected wi th HIV in utero, at delivery or during breastfeeding. 8 Interventions to reduce mother to child HIV 1 transmission to less than 2% include antiretroviral therapy, elective cesarean section ( C section ) at delivery and safe alternative methods of infant feeding. In the absence of any interventions, mother to child HIV 1 breastfeeding transmission rates range from approximately 15% 45%. 8 9 Roughly 17 million HIV positive mothers the majority of which living in Africa and South East Asia, face the challenging decision of whether or not breastfeeding is the best option for themselves and their child. HIV/AIDS is a leading cause of death in endemic areas of developing nations; disease infectivity remains a multifaceted i ssue. According to the WHO in 2015 approximately 36.7 million people were living with HIV with 2.1 million people becoming newly infected two thirds of which in Sub Saharan Africa This region is th e most af fected globally with 25.5 million peop le living with HIV 6 Of the 36.7 million people living with HIV in 2015, only 18.2 million people were receiving antiretroviral therapy drugs worldwide by mid 2016 which is roughly 50% of the infected population 6

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES ( I n HIV endemic population s there continues to be major public health issue s regarding women who are HIV positive HIV positive women have many risks and barriers in the context of overall nutrition status, coupled with social and economic is sues which pose difficulty in determining whether or not to breastfeed. Mothers do not want to pass onto their childr en a painful terminal and chronic disease of which life expectancy is shortened A lthough, if alternative methods of infant feeding are used the risk of infant morbidity and mortality consequently increases from a combination of malnutrition, vitamin deficiencies, and additional infectious disease. In 2015, approximately 17 .8 million women were in fected with HIV globally and 15 0,000 children became newly i nfected during the course of the year 7 Death follows in the footsteps of an HIV diagnosis particularly in developing countries Accor ding to a 2015 g lobal f actsheet provided by The Joint United Nations Programme on HIV/AIDS ( UNAIDS ) there were 1 .2 million deaths due to AIDS which included 110,000 deaths of children aged 0 14. 7 In 2015, there were 13 .4 million orphans aged 0 17 as a result of caregivers dying from the disease. 7 These numbers are substantial and can in theory be reduced In 2001, 800,000 children under the age of 15 c ontracted HIV and over 90% of them (720,000 children) from mother to child HIV 1 transmission. 8 The above statistic is dated and many efforts have been made to reduce vertical HIV 1 transmission rates at the global and public health level. Even with efforts aimed at reducing mother to child HIV 1 transmission, HIV/AIDS is sti ll a prominent issue affecting millions of people annually therefore risk of t ransmission is still prevalent especially in developing countries Various other issues further complicate the decision for a n HIV positive mother to breastfeed her infant. Numerous nutrition al interactions concerning micronutrient intake,

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES ) macronutrient intake, and overall maternal nutrition status can increase or decrease the r isk of mother to child HIV 1 transmission via breastfeeding. Social restraints also play a role includ ing social stigmatization of HIV positive women, HIV disclosure and non disclo sure low health literacy rates and superstition s within cultural groups Women who are HIV positive also have economic concerns ; some of which include cost of alternative feeding methods, and access to antiretroviral treatment drugs among other barriers. The WHO states that in 2015, 77% of all pregnant women livin g with HIV globally received antiretroviral therapy to prev ent mother to c hild HIV 1 transmission, alth ough, there is no specificity to the location of these women worldwide 10 I n the last twenty years, mother to child HIV 1 transmission rates have decreased significantly in develo ped nations. With the use of appropriate interventions, vertical HIV 1 transmission rates of less than 2% have been reported in European and North American populations. 1 1 Therefore, based on transmission rates on a global scale HIV positive women living in developed nations are most likely r eceiving appropriat e care to reduce risk of mother to child transmission of HIV Alternatively, HIV positive women in developing co untries are not receiving the same preventative and protective care. Per nutrition research and data b reastfeeding provides various nutritional, immune, and long term benefits for the infant, coupled with a variety of maternal benefits. T he choice to br eastfeed will pose a controversial and difficult decision for HIV positive mothers regarding risk of HIV 1 transmission According to the 2016 WHO updated guidelines on HIV and infant feeding, even when antiretroviral drugs are not available, HIV positive mothers should exclusively breastfeed in the first six months of life and continue breastfeeding thereafter unless environmental and social circumstances are safe and supportive of replacement feeding

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES methods. 1 2 In circumstances when antiretroviral therapy drugs are unlikely to be available for mothers, breastfeeding of infants is recommended to increase infant survival. 12 Various global and national policy statements on the issue directly correlate to the health and welfare of HIV positive mothers and infa nts in developing countries. In the United States the general consensus is that HIV is a notable contraindication for breastfeedin g. 13 Generally, practitioners in the field will d iscourage breastfeeding with an HIV positive diagnosis. 13 The American Acade my of Pediatrics stance on HIV positive mothers and breastfeeding states that "in the industrialized world, it is not recommended that HIV positive mothers breastfeed. 13 Alternatively, current global health policy and recommendations promote exclusive breastfeeding, even if HIV positive Although policy is set to aid the broad population it serves, sometimes the set forth procedures and strategies prove to b e unsuccessful. For example, the greatest declines in breastfeeding have taken place in countries where infant formula has been distributed at no cost by national and local authori ties in order to prevent mother to child HIV 1 transmission. 1 4 Although the policy sought to improve the lives of its citizens, an unforeseen consequence of the program was tha t even mothers who were not HIV positive turned to infant formula, therefore decreasing breastfeeding rates altogether. 1 4 With a culturally appropriate understanding of these complex issues, determination of whether or not women who are HIV positive should breastfeed will be discussed in conjunction with dissimilar global health policy in developed and developing nations Overall, this thesis will seek to establish if breastfeeding is culturally and healthfully a ppropriate for mother and infant while determining the effectiveness of current global health policy statements and recommendations

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "+ Issues in Developing Count r ies I. Benefits of Breastfeeding According to The Centers for Disease Control and Prevention's ( CDC ) most recent data: in 2011 79% of newborn infants were started on a breastfeeding regimen in the United States. 1 5 However, breastfeeding did not continue for as long as recommended. Of the infants born in 2011, 49% were still being breastfeed at six month s and only 27% at twelve months. 1 5 For various reasons, women in the United States do not breastfeed for the recommended amount of time aimed at maximizing benefits for mother and infant. UN ICEF provides data denoting exclusive breastfeeding percentages of infants 0 5 years of age (provided in the picture below). 1 6 Source: UNICEF global databases, 2016, based on MICS, DHS and other nationally representative sources, 2010 2016 (*denotes countries with older data between 2005 2009; data form these countries are not included in the regional aggregates except for China (2008) which is used for the East Asia and the Pacific and World averages). Countries shaded in dark grey have est imates from 2004 or earlier; these countries are not included in the regional or global aggregates. From the above data, speculation can be made that a greater proportion of developing countries breastfeed infants for at least five months compared to deve loped countries Observing the data, only 43% of mothers worldwide breastfeed their infants exclusively for five months. 16 Exclusive breastfeeding (no supplemental food or liquid) provides complete nutrition for the

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "" infant's first six months of life, and s hould be continued for at least one year with complimentary food added at six months or when the infant is de velopmentally ready. 1 7 According to the Academy of Nutrition and Dietetics, breastfeeding provides the best possible nutrition for an infant beca use breastmilk contains factors which serve both nutritive and non nutritive functions. 1 8 It has been well documented that the high bioavailability of essential vitamins and minerals found in breastmilk are best served for the immature digestive system of an infant compared to alternative methods of infant feeding 1 8 Human milk is uniquely suited to the infant ; the b reastmilk changes in composition starting with colostrum to late lac tation, and varies within feeds 1 9 Bre a stmilk provides growth hormone, and contains the p roper ratio of protein, fat and carbohydrate, which change through out infant growth in order to best serve the infants nutritional needs 1 9 Additionally, b reastmilk provides maternal immune factors which help to develop the gut microbiome of the infant while also protect ing against disease 1 8 Breastfed infants have a decreas ed prevalence of ear infections, respiratory illness, sudden infant death syndrome as well as other health conditions later in life including obesity and hypertension. 1 8 Also, Bre astfeeding distinctively supports healthy brain development, increases IQ and is associated with improved educational achievement at age five years old and beyond 20 In addition to the numerous benefits for infants, breastfeeding also provides various maternal benefits. Immediate skin to skin contact and early initiation of breastfeeding after delivery can reduce r isk of maternal post partum hemorrhage while increasing compliance and ea se of futur e breastfeeding 21 B reastfeeding additionally re duces risk of breast, uterine and ovarian cancers, and aids in weight loss after delivery for the majority of mothers 18 20 Various

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "# studies also suggest an association between early cessation of breastfeeding and an increase of maternal post natal depression. 20 In developing countries, the benefits of exclusive breastfeeding stretch further. In addition to the previous listed benefits for mother and infant, in developing countries early and exclusive breastfeeding significantly reduces risk of infan t morbidity and mortality According to UNICEF, a child who is exclusively breastfed is 14 times less likely to die in the first six months of life than a non breastfed child. 20 The t wo leading causes of infant morbidity and mortality in developing countri es include acute respiratory infections and diarrhea. 20 Exclusive breastfeeding drastically reduces the incidence of both. Every year, approximately 4.9 million children between the ages of 28 days and five years old die primarily in developing countries 2 Of the 4.9 million children, 28% die from diarrhea and pneumonia (table) 2 Source: The Partnership for Maternal, Newborn and Child Health. Newborn death and illness. http://www.who.int/pmnch/media/press_materials/fs/fs_newborndealth_illness/en/ Updated September 2011. Accessed March 2, 2017. D iarrhea ranks hig h on causes of infant mortality P redominant breastfeeding would red uce prevalence of diarrhea l prevalence by about 56 % in the first five months of life and

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "$ would reduce infant mortality attributed to diarrhea by 78 % 3 In the review article, Breastfeeding and the Risk for Diarrhea Morbidity and Mortality formula fed infants 0 5 months of age had a relative risk ratio of 4.90 for prevalent diarrhea when compared to partially breastfed infants who had a risk ratio of 2.15 roughly half the risk of not breastfeeding at al l 3 Partially breastfe eding infa nts is not as preventative as exclusive breastfeeding Partially breastfe d infants are supplemented with additional food and water sources which can increase risk of diarrhea l prevalence from bacterial contamination Infants in the first five months of life who were predominantly breastfed (RR: 2.28), and partially breastfed (RR : 4.62 ) had a 78% 56% decreased risk of mortality from diarrhea l episodes 3 Breastfeeding in any capacity reduces risk of infant death from dehydration caused by diarrhea In addition to diarrhea, p neumonia and other respirato ry infections are also widespread causes of infant death occurring much more frequently in developing countries 2 While 14% of child deaths under the age of five can be attributed to pneumonia, breastfed infants are 47% times less likely to die of a respiratory infection such a pneumonia than non breastfed infants B reastfeeding is also associated with a 74% lower risk of pneumonia related hospitalizations and a reduced r isk of lower respiratory infections up to four years of age. 4 5 Therefore, breastfeeding in developing countries can reduce instances of respiratory infection as well as diarrhea l occurrence thus contributing to increased survival rate s of children under the age of five years old Poor nutrition status and malnutrition account for significant rate s of child and infant death annually. Over one third of all child deaths are linked to malnurition 2 Stunting can occur from poor nutrition in the first thousan d days of a child's life, and is associated with impaired cognitive ability, and an increase in frequency and severity of common infections. 2 2 Exclusive

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "% breastfeeding for the first five months of life decreas es the instance of stunting, wasting and malnutr ition by an average of 12.2 %. 2 3 Children are not receiving appropriate nutrition early in their lives, they are therefore suffering from malnutrition, stunting and wasting. I n 2016, the majority of stunted childr en were localized in South East Asia 46% and Africa 70% 22 Although 57% of sub Saharan Africa and 90% of South E ast Asia exclusively breastfeed for up to five months, proper nutrition after breastfeeding cessation may not be achievable therefore increasing malnutrition rates in poverty stricken locations for children up to five years of age 16 (reference picture below). Source: UNICEF, WHO, World Bank Joint Child Malnutrition dataset, September 2016 update M orbidity and mortality of infants and children up to the age of five frequently occur from bact erial and respiratory infection Both of which can be reduced considerably with exclusive breastfeeding practices T herefore increasing rates of exclusive breastfeeding is warranted in developing countries in order to reduce infant death B reastfeeding is the gold standard method of infant feeding, although, certain contraindications discourage mothers from breastfeeding and health professionals from recommending breastfeeding One prominent reason

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "& not to breastfeed is HIV infectivity because the virus can be transmitted from mother to child via breastmilk. II. Breastfeeding with HIV/AIDS With high prevalence of HIV /AIDS in developing nations, specifical ly sub Saharan Africa, many HIV positive mothers are ex pected to make a decision to either refrain from, or in itiate breastfeeding after delivery HIV 1 can be vertically transmitted three different ways: in utero, at delivery and through breastfeeding. Mother to child HIV 1 transmission has been well docume nted s in ce the HIV/AIDS epidemic began. In the late 1 980' s early 1990's t he first reports of HIV 1 transmission via breastmilk were of infants breastfed from women who had been infected postnatally through blood transfusions or through sexual intercourse after delivery 24 Additionally, infants with no other known exposure to HIV, became infected through wet nurses or pooled breastmilk. 24 Over the last thirty years, various research has sought to determine a statistical risk of transmiss ion via breast feeding, although, rates differ substantially. 24 There are varying statistics delineating the risk of HIV 1 transmission via breastfeeding It is difficult to determine whether or not an infant becomes infected during delivery (intrapartum), or through early breastfeeding with current technolog ical methods of HIV diagnosis 24 In the absence of any intervention, which may include antiretroviral treatment for mother and infant elective caesarian section ( C section ) and avoidance of breastfeeding, the overall mo ther to child transmission rate is approximately 20% 40% 25 V ertical HIV 1 transmission risk estimations find that 10% 25% of transmission s occur during pregnancy, 35% 40% during labor and delivery and 35% 40% during breastfeeding. 26 According to other studies transmission rates via breastfeeding alone are between 15% 45%. 8 9

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "' Observing the table below even if an HIV positive mother choose s not to breastfeed her child, there is still a risk of 15% 30%. This is attributed to probable intrapartum transmission, but cannot be specifically measured, therefore, rates of transmission risk via breastfeeding are many times lower. 24 However, t ransmission rates gradually increase with added duration of breastfeeding (table 1). 9 ,24 2 6 Source: Cock K, Fowler M, Mercier E, de Vincenze I, Saba J, Hoff E, et. Al. Prevention of mother to child transmission in resource poor countries, translating research into policy and practice. JAMA 2000;283:1175 1182. Breastfeeding pose s a clear risk of potential HIV 1 transmission from mother to infant depending on duration and method of feeding associated Many mothers would prefer not to breastfeed their child for fear of infecting them with HIV 1 Although, if not breastfed, the infant will then be more likely to die of respiratory or diarrheal disease The choice to breastfeed while HIV positive increases the risk of infants' contracting a fatal and chronic disease H owever, the increased chance of infant survival from the benefits of breastfeeding will therefore pose a difficult decisi on for any HIV positive mother. HIV/AIDS is a historically relevant issue across Africa and other developing nations. HIV (human immunodeficiency virus) can lead to AIDS (acquired immunodeficiency syndrome) C hronic HIV ranges in symptoms of weight loss, diarrhea, high fever, and can progress to more severe symptoms with AIDS. 2 7 HIV/AIDS is not curable, only treatable. HIV

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "( attacks the body's immune system, specifically targeting CD4 (T cells), which help the immune s ystem fight off infections. 2 7 If left untreated, HIV reduces the number of CD4 ce lls in the body making a person more likely to develop infections or infection related cancers. 2 7 Over time, HIV can destroy so many CD4 cells that the body is unable to figh t off infections and disease. 2 7 These opportunistic infections or cancers take advantage of a person's weak immune system. When the immune system is so drastically altered and CD4 cell count falls below 200 cells per cubic millimeter of blood (200 cells/mm 3 ) the person is then considered to have AIDS. 2 7 AIDS is also diagnosed when a person develops one or more opportunistic infections, regardless of CD4 cell count. 2 7 HIV can progress to AIDS with in 10 years without appropriate treatment in any population 2 7 The prognosis for someone who is diagnosed with AIDS is roughly around three years. 2 7 If the opportunistic infections are dangerous, life expectancy falls to about one year. 2 7 There is no effective cure for AIDS currently, but with p roper treatment and medical care, HIV can be controlled and antiretroviral therapy can prolong the lives of people living with HIV, as well as decrease rates of transmission in any context 2 7 28 Infants in particular can benefit from antiretroviral therap y drugs Research suggests that if infants are tested at six weeks postpartum, and on treatment by twelve weeks postpartum, there can be a 75% reduction in infant mo rbidity and mortality due to HIV/ AIDS. 2 9 National governments, and external donors (U .S. and other developed countries ) have attempted to supply antiretroviral medication targeting the HIV positive maternal infant population in order to reduce vertical transmission rates 30 31 Even though attempts have been made to decreas e the rate of ver tical HIV 1 transmission, looking specifically at South Africa, preventative measures have not had the impact the government was expecting According to

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES ") UNAIDS in 2014 6 8 million people were living with HIV in South Africa 3 .9 million were females over the age of 15. 3 2 The WHO states that in 2014 263,674 women in South Africa received antiretroviral medication in order to prevent mother to child HIV 1 transmission although, this is only 6.7% of the female HIV positive population. 33 Assump tions can be made that more than 6.7% of the female HIV positive population is reproducing, therefore there is still likely risk of vertical HIV 1 transmission even with efforts to distribute antiretroviral medication to this at risk populations The prog nosis for someone with limited or no access to appropriate healthcare is not favorable. Therefore, i n order to decrease vertical HIV transmission risk via breastfeeding m any HIV positive mothers use alternative methods of infant feeding Infant formula, cow and/or goat milk or heat treating expressed breastmilk are all alternatives to breastfeeding, but have specific risks associated to each method III. Alternative Methods of Infant Feeding Many HIV positive women living in sub Saharan Africa come from very low socioeconomic status which makes obtaining safe alternative infant feeding products difficult because of financial constraint Looking specifically at South Africa an endemic area that has the largest prevalence of HIV/AIDS t he household median income for the black African population is roughly between R60,000 ($4,459.14 USD) and R34,078 ($2,532 USD) per year. 3 4 Half of all black Africans are earning below and half are earning above this estimate annually Black Africans make a sixth of the household income of a white family, but make up 80.2% of the overall population. 34 3 5 Using the low end of median annual income per black African household in South Africa at roughly R34,100 ($2,534 USD), the average m onthly income averages out to about R2,841.66

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES "* ($2 11.14 USD) The price of infant formula in South Africa range s from R47.95 (3.74 USD) to R 4,161.00 (324.19 USD). 3 6 The most common infant formula s purchased in S outh Africa are sta rter formulas, most frequently Nan which is produced by Nestle. 3 7 The cost of Nan Stage 1 Starter Infant Formula (900g) is R157.00 ($11.68 USD). 3 8 As a single example, an infant during the 2 nd and 3 rd months of life require s seven scoops per day of the Nan Stage 1 Starter infant formula mixed with water 3 9 In a singl e day an infant should receive 4 5 feedings which aggregates a range of around 100 g 1 30 g of infant formula per day. In one week a mother utilizing Nan Stage 1 Starter Infant Formula should use between 70 0 g and 900 g of infant formula. In a little over one week the infant formula should be fully utilized. With an average monthly income of R2 841.66 ($211.14 USD), purchasing infant formula once per week will consume roughly 22% of the monthly household income. Infant formula will become more expensive as time progresses until around six months of age, or when the infant is developmentally ready for the addition of complementary foods The cost of almost $12.00 USD per week for infant formula may not seem like a substantially high number, although, the cost of living in South Africa is relatively high an example of the average cost of 1 gallon of milk is R50.69 ($3 .77 USD) 40 C onsequently, there is little room for extra expenses Infant f ormula as a substitute for breastfeeding may not be a feasible and cost effective alternative for some HIV positive mothers and/or families T he median income for a black African household is low, and the cost of infant formula is quite high, therefore, some mothers will use infant formula on the basis of quantity rather than quality This stems from lack of knowledge about proper infant feeding or lack of knowledge regarding the infant's nutritional needs 41 The mother may neglect proper infant feeding

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #+ recom mendations, and make the infant formula last as long as possible by watering the amount of infant formula down causing dilution These mothers may not realize that the infant is not receiving the appropriate nutrition al requirements needed for growth 41 The child may then be classified as non organic failure to thrive, therefore increasing chance of protein energy malnutrition and infant death. This method of feeding is extremely dangerous. While it is necessary to utilize water to mix i nfant formula t his may cause deadly barriers for many women of low socioeconomic status in developing countries If infant formula is used as a replacement feeding method infants are at increased risk of death from bacterial contamination causing diarrhea and therefore death by dehydration. According to the United Nations, in 2012 there were 748 million people relying on unsafe water sources, 173 million people obtained their drinking water straight from rivers, streams or ponds. 4 2 However, unclean water and sanitation is predominantly localized in rural and poverty stricken areas; s even out of ten people without access to sanitary facilities live in rural areas. 4 2 Many drinking water sources are not easily accessible to numerous households in developing countries and are microbiologically contaminated, consequently increasing risk of diarrhea l episodes in infant s who are consuming the water several times per day. 42 International organizations, such as the WHO, USAID and the World Bank have increased programs to thwar t unsafe drinking water and increase hygienic practices specifically in HIV/AIDS endemic areas. 43 4 7 Through these programs, there have been instances of reduced bacterial contamination thus decreasing diarrhea l episodes. A trial in Uganda found that house hold chlorination technology in HIV positive households had a 25% reduction of diarrhea l episodes and 33% fewer days with diarrhea compared to the control group. 4 8 Additionally, significant associations with diarrhea reduction and chlorination technology have been found in

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #" Nigeria among adults with HIV/AIDS and in Kenya regarding infants born to HIV positive mothers. 49 50 Conversely, these programs have typically been in the form of chlorination products, which do not inactiv ate or kill the extensive diversity of waterborne pathogens 51 T herefore the use of disinfectants alone cannot be expected to eliminate all bacterial waterborne pathogens. Although there has been an increase in drinking water chlorination technology aimed at reducing bacterial contamination, there is evidence to assume that more needs to be done in order to reduce diarrhea caused by bacterial pathogen s in drinking water In a random cluster household survey study conducted in Abidjan, C™te d'Ivoire, a colle cted source of stored drinking water samples were tested for chlorine levels and fecal bacteria count in 120 households 5 2 Although 93% of the study population utilized municipal water for drinking, 83% of the population stored it for later use. 5 2 Approxim ately 90% of the 108 infants by one month of age who were given drinking water were given the stored water. 5 2 In 12 of the households 66% of infants were receiving infant formula prepared with the municipal water without additional treatment. 5 2 The stored water had lower levels of free chlorine than the source water, and E. coli was detected in 41% of 87 stored water samples, but only in 1% of 108 source water samples (Table 1). 52 Source: Dunne E, Angoran BŽniŽ H, Kamelan Tano A, Sibailly T, Monga B, Kouadio L, et al. Is drinking water in Abidjan, C™te d'Ivoire, safe for infant formula? J Acquire Def ic Syndr 2001;28(4):393 8.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES ## Although municipal water is provided to this community as a so urce for safe drinking water, the majority of the population store d the water for later use which includ ed infant formula Storing municipal water consequently perpetuat es bacterial contamination and increas es risk of diarrhea l episodes in the infant population and therefore morbidity and mortality Unsafe drinking water is a significant cause of death, especially for infants of low socioeconomic status People with HIV/AIDS are extremely susceptible to opportunistic infections from wa terborne pathogens therefore s afe water is critical for HIV positive mother s who choose to utilize infant formula as a replacement feeding method In the study, Drinking Water Quality, Feeding Practices, and Diarrhea among Children Under 2 Years of HIV Po sitive Mothers in Peri Urban Zambia 26% of children under two years of age had diarrhea in the past week and bacterial contamination of drinking water was found in 70% of households. 5 3 The risk of death from diarrhea caused by contaminated water may outwe igh the risk of HIV transmission via breastfeeding in the majority of low socioeconomic settings particularly in developing countries Additionally, t he use of cow milk is an inappropriate alternative to exclusive breastfeeding and is dangerous Cow milk is for baby cows, not baby humans. There are varying differences between human milk and cow milk. If cow milk is used as the primary, or only form of replacement feeding, certain nutritional issues and deficiencies will arise. According to a case control study in Batswana (below picture) approximately 40% of infants were receiving neither breastmilk nor formula but instead rec eived a variety of substitutes including pasteurized and unpasteurized cow milk. 5 4

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #$ Source: Arvelo W, Kim A, Creek T, Legwaila K, Puhr N, Johnston S, et al. Case control study to determine risk factors for diarrhea among children during a large outbreak in country with a high prevalence of HIV infection. IJID 2010;14:e1002 e1007. In 1 fluid ounce of whole cow milk, there are 2 ki localories less than in human breast milk, with 33% more protein. 17 The protein in cow milk is significantly different from human breastmilk The predominate protein found in cow milk is casein, which accounts for about 80% of total protein. 5 5 Conversely, in human breast milk whey protein account s for 60 70% of total protein. 5 5 Whey protein is more easily digestible than casein protein, and actively protect s against bacteria therefore decreasing risk of bacterial infection while increas in g infant immunity 17 55 Additionally, lipid profiles vary among human and cow milk. In cow milk, saturated fatty acids account for the majority of fat composition where unsaturated fatty acids account for the majority of fat composition in human breast milk. Cow milk is also higher in so dium, potassium and phosphorous than in human breastmilk 17 The high electrolyte composition in cow milk is difficult for an infant 's premature kidneys to effectively process. The renal solute load of high electrolyte con centration s coupled with the high casein protein in cow milk leads to a higher urine osmolar concentration three times higher than that of human breastmilk. 5 6 The renal concentrating ability of an infants kidneys may be insufficient for maintaining water balance, and therefore severe dehydration may result. 5 6

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #% Cow milk also differs in micronutrient composition. The bioavailability of micronutrients found in cow milk are not as bioavailable as micronutrients in hum an breast milk. 17 In 100g of cow milk, there is <5mg of iron, and only about 10% of the <5mg of iron is absorbed by the infant. 5 7 There is also no ascorbic acid (vitamin C) in cow milk. Vitamin C increases iron absorption, therefore lack of vitamin C perpet uates the low bioavailability of iron found in cow milk. Furthermore, cow milk form s a curd in the stomach of infants causing bleeding and occult gastrointestinal blood loss blood which is not visible in fecal stool samples Occult gastro intestinal blood loss happens in roughly 40% of infants fed cow milk. 5 8 The combination of no vitamin C occult gastrointestinal blood loss and low bioavailability of iron directly contributes to higher potential of develop ing iron deficiency anemia. In comparison to cow milk, goat milk has approximately the same nutritional composition, with a few notable differences. In general, goat milk contain s less lactose, fat and protein than cow milk, but has similar mineral and electrolyte content. 5 9 The most notable diffe rence between the two is the lack of folic acid in goat milk. In addition to the other risk factors listed previously concerning cow milk, the lack of folic acid in goat milk will cause megaloblastic anemia, therefore increasing infant comorbidities, and p otential infant death. 60 The nutritional composition of both cow and goat milk pose distinctive, individual risks. There are also non nutritive risks to use of cow or goat milk as alternative feeding methods A primary issue with both breast milk substitutes is the use of unpasteurized products which contribute to an increased risk of food borne illness. 61 Pathogens commonly transmitted through food disproportionately impact children younger than five years old. 6 2 The child and infant population faces higher risk of foodborne pathogen exposure because their immune systems are less developed, and have limited ability to fight infections. 6 2 Additionally, an infant's lower body

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #& weight reduces the amount of pathogen needed to cause illness 6 2 If these infants are not breastfed, risk of infection increases because maternal immune factors are not present to protect against pathogens The WHO estimates that approximately 125,000 children under the age of five years old die annually f rom foo dborne illnesses with the highest burden in African and South East Asian populations. 6 3 This accounts for almost 3 0% of all deaths attributed to foodborne illnesses globally, despite the fact that children under five years old make up only 9% of the global population. 6 3 M ost notable pathogens include bacteria, viruses, helminths, toxins and chemicals. 63 Around 220 million children under the age of five fall ill and 96,000 die every year from foodborne diarrheal pathogens including: norovirus, Campylobacter non typhoidal Salmonella and pathogenic Escherichia coli 6 3 Diarrheal diseases are responsible for roughly 70% of foodborne illnesses in the African region, of wh ich Salmonella specifically causes the most deaths. 6 3 Raw or unpasteurized milk products carry dangerous bacteria including Salmonella Escherichia coli and Listeria throughout the world 6 4 These pathogens can cause adverse health e ffect s in anyone consuming the raw product U npasteurized milk can be even more dangerous to pregnant women and children, especially with weakened immune system s caused by HIV/AIDS. 6 4 In addition to the issues of unpasteurized milk products, other limitations aris e. Women who are using cow and/or goat milk as an alternative to breastmilk need to consider the cost associated as well as access to appropriate storage and refrigeration As a single example in a periurban settlement in South Africa, 70% of eighty four HIV positive mothers did not have

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #' access to refrigeration. 6 5 Lack of refrigeration increases risk of further contamination of cow and goat milk. Heat treating expressed breast m ilk is another alternative method of infant feeding. Heating expressed breastmilk to a high temperature in a very short amount of time can be done with simple tools in a home setting This method of alternative infant feeding is a feasible and safe option for many HIV positive mothers. Flash heating expressed breast m ilk retai ns the majority of the breastmilk's nutrient profile and maternal immune factors, while killing the HIV 1 virus. In the study, Vitamin Content of Breast Milk from HIV 1 Infected Mothers Before and After Flash Heat Treatment fifty HIV positive mothers in Durban, South Africa manually expressed 75 150 mL of breastmilk into sterile jars. 6 6 The milk was allocated to unheated controls or flash heated. 6 6 The samples were then analyzed to determine the micronutrient concentrations in unheated and flash heated expressed breastmilk. 6 6 Vitamin A was not significantly affected by the flash heating method, however, vitamins B 12 C and folate increased. 6 6 In contrast vitamins B 2 and B 6 were decreased to 59%, than that of unheated milk. 6 6

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #( Source: Israel Ballard K, Abrams B, Coutsoudis A, Sibeko L, Cheryk L, Chantry C. Vitamin content of breast milk from HIV 1 infected mothers before and after flash heat treatment. J Acquir Immune Defic Syndr 2008;48(8):444 449. It is hypothesized that the post heat increase in ascorbic acid, folate and vitamin B 12 concentrations compared to unheated samples can be caused by heat induced release of vitamins from binding proteins in the breastmilk. 6 6 The vitamins above were selecte d in the study because of their essential role in the maternal infant dyad during lactation. 6 6 In addition to micronutrient composition being relatively unchanged in flash heated breast m ilk samples the majority of maternal immune factors are also retaine d Fifty HIV positive mothers in South Africa provided breastmilk, part was unheated as a control, and the remainder was flash heated. 6 7 Total antigen specific IgA and IgG were measured to detect the amount of maternal immune factors kept intact after flas h heating breastmilk samples. 6 7 In fifty analyzed samples, flash heat ed breastmilk induced a statistically significant decrease in total IgA (20%), and a decrease in IgG (33%). 6 7 Although there is a notable reduction of maternal immune factors in flash heated breastmilk samples most maternal immune factors in breastmilk survive. 6 7 Therefore, f lash heating breastmilk is far superior to other breastmilk substitutes because most maternal immune factors are kept intact The use of flash heating expressed breastmilk kills the HIV 1 virus. In order to inactivate both cell free and cell associated HIV 1, temperature of the breastmilk needs to reach at least 65 ¡ C but not over 70 ¡ C, in order to retain breastmilk s nutrient co mposition and maternal immune factors. 6 8 In the stu dy, Flash Heat Inactivation of HIV 1 in Human Milk ninety eight breastmil k samples were collected from eighty four HIV positive women located in South Africa. 6 9 The breastmilk was either unheated as a control, or flash heated. Reverse transcriptase assays were used to detect ac tive and inactive cell free HIV. 6 9 All flash heated samples showed undetectable levels of cell free HIV 1. 6 9 The use of flash heated expre ssed breastmilk can

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #) effectively inactivate HIV in infected breastmilk. 6 9 Heat treating expressed breastmilk as an alternative method of infant feeding may be a feasible option for HIV positive women that carries virtually no risk of mother to child HIV 1 t ransmission while providing the many benefits of breastmilk. Heat treating expressed breastmilk does pose potential limitations and risks regarding compliance, methods and storage There is an eight point protocol regarding heat treating expressed breastmilk: 1) wash hands with soap prior to expressing; 2) clea n jar and feeding cup with soap; 3) sterilize jar and feeding cup by boiling; 4) express milk into glass jar; 5) express from both breasts; 6) place the jar in a pot with sufficient water to c ome two finger widths above milk level and heat until water reaches a rolling boil; 7) remove pot as soon as water boils; 8) immediately remove jar from pot and cover. 70 Mothers are then instructed by nursing personnel and other health professionals to fee d the heat treated expressed breastmilk within eight hours, which is the shelf life at room temperature. 71 Many people live w ithout access to refrigeration and cannot appropriately store the expressed heat treated breastmilk, therefore making this option a less likely candidate for alternative feeding methods if proper storage cannot be attained If HIV positive mothers do not adhere or comply with all eight steps listed above ris k of negative outcomes may arise. If women do not have access to soap and cl ean water for washing hands before expressing and to wash fe eding cups and other vessels risk of bacterial contamination increases. If mothers do not heat the expressed breastmilk for the appropriate amount of time HIV 1 virus will still be present. If heated too long, or at too high of a temperature, the micronutrient and maternal immune factor composition of the breastmilk will

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES #* decrease. Therefore, compliance is necessary in order to use heat treating expressed breastmilk as an alternative infant fe eding method. Certain cultural taboos and superstitions may also play a role in the use of heat treating expressed breastmilk. In the study, Acceptability of Heat Treating Brea s t Milk to Prevent Mother to Child Transmission of Human Immunodeficiency Virus in Zimbabwe: A Qualitative Study seventy seven study participants (men and women who did not disclose HIV status) participated in thirteen focus group discussions in three demographic regions of Zimbabwe. 7 2 Focus groups discussed topics including : the cu rrent practice and understanding of manual expression of breast milk, knowledge of flash heating as a method to reduce mother to child HIV 1 transmission, cultural perceptions, and required resources Discussion topics also referenced community and financia l support, education or counseling regarding heat treating expressed breastmilk, and the overall potential to accept this as a an alternative method of infant feeding 7 2 While 30% of female participants noted that they had expressed breastmilk at some point during lactation, o nly 6% of participants were aware that heat treating expressed breastmilk could prevent HIV 1 transmission 7 2 Most participants, male and female, were concerned that manually expressing breastmilk would disrupt the bo nd between m other and child, which would otherwise strengthen if breastfeeding. 7 2 Participants believed that only a breastfeeding child was capable of recognizing its mother by touch, voice, and smell. 7 2 In rural and suburban settings the most common ly cited belief w as that a non breastfed infant was acting as a prophet to reveal that either the mother or the father had been unfaithful. 7 2 In various areas of Zimbabwe, infants who refuse' to nurse, and thus receive expressed breastmilk, are said to suffer until a moth er confesses her wrongdoing. 7 2 Furthermore women who are non breastfeeding and express breastmilk, are also viewed as

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $+ witches. A lot of suspicion will be raised people may think the women is a witch and wants to feed her breastmilk to snakes, goblins, a nd hyenas. 7 2 Another notable cultural taboo in all groups involved in the study is the concept of one becoming contaminated by touching human milk Vessels that hold expressed breast milk, including bottles, cups or pots are then considered contaminated. 7 2 This now contaminated vessel could affect anyone entering the home according to several midwives and birth attendants in the study. 7 2 The negative social implications of heat treating expressed breastmilk as an alternative to breastfeeding in order to re duce, or potentially eliminate the risk of vertical HIV 1 transmission via brea stfeeding are serious. With these health belie fs, certain consequences can arise including the community accusing the women of being a witch or adulterer thus causing these wom en to be stigmatized and ostracized with in their communities and families The graph on the following page depicts the percentage of people in the study who correlated expressing breastmilk to witchcraft, contamination, or adultery.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $" Source: Israel Ballard K, Maternowska C, Abrams B, Morrison P, Chitibura L, Chipato T, et al. Acceptability of heat treating breast milk to prevent mother to child transmission of human immunodeficiency virus in Zimbabwe: a qualitative study. J Hum Lact. 2006;22(1):48 60. In some communities the use of flash heating expressed breastmilk to aid in reduction of vertical HIV 1 transmission via breastfeeding may be the best option. Alth ough, in other communities, such as parts of Zimbabwe, it may n ot be socially and culturally appropriate. Overall, with proper education and accessible methods for compliant flash heating of expressed breastmilk, this option may be extremely beneficial in certain populations

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $# Some mothers may consider partially brea stfeeding by using an alternative method of infant feeding in addition to breastfeeding to reduc e cost while also trying to reduce mother to child HIV 1 transmission HIV positive mothers may assume that there is a decreased risk of transmission if they are not exclusively breastfeeding Although, th is mixed method of feeding is dangerous and can actually increase risk of mother to child HIV 1 transmission via breastfeeding 7 3 It has been suggested that exclusive breastfeeding with HIV could be associate d with decreased r isk of HIV 1 transmission compared to mixed feeding methods of both breastmilk and an alternative method of infant feeding In Durban, South Africa, a prospective cohort study looked at the risk of HIV 1 transmission by infant feeding mo dality. A total of 551 HIV infected women self selected to breastfeed or formula feed after being counseled to breastfeed for 3 6 months. 7 4 Of the 551 HIV positive women, 157 formula fed, 118 exclusively breastfed, and 276 used mixed methods of feeding. 7 4 Infants who received both breastmilk and alternative feeding methods were more likely to be vertically infected via breastfeeding by 15 months of age (36%), than infants exclusively breastfed for at least three months (25%) or infants who had been exclusi vely formula fed (19%). 74

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $$ Source: Coutsoudis A, Pillay K, Khun L, Spooner E, Tsai W, Coovadia H, et al. Method of feeding and transmission of HIV 1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001;15:379 387. The attributed cause of increased risk of vertical HIV 1 transmission by mixed feeding methods has been hypothesized yet nothing has been confirmed. It has been theorized that the association can caused by increased gastrointestinal permeability, or local inflammation in the infant 7 4 Another hypothesis is an increase in subclinical mastitis. It is thought that women who are continually mix feeding their infants may be practicing suboptimal breastfeeding pr actices and therefore have a higher association of subclinical mastitis thus increasing risk of vertical HIV 1 transmission via breastfeeding 7 5 As discussed previously, the use of alternative feeding methods will increase risk of comorbidities, t herefore increasing the risk of infant morbidity and mortality. Even if a woman is HIV positive, exclusive breastfeeding is the best option to decrease infant morbidity and mortality. IV. Stigma Association One's HIV status disclosure is imp ortant in coping with the disease and understanding the surrounding implications of the chronic condition In order to prevent HIV/AIDS and mitigate its impact disclosure is critical. The use of alternative feeding methods also poses a substantial risk to HIV positive mothers in a different context In countries where HIV/AIDS is widespread stigma greatly complicates treatment and prevention. The stigma associated with an HIV/AIDS diagnos e s often motivates people to avoid disclosing their HIV status. Disclosure of HIV status can promote stigmatization causing people to be frequently ostracized from their homes and communities. A dditionally HIV related stigma is associated with h igher levels of depression, and lower quality of life overall. 7 6 It has been estimated that over 50% of mother to child HIV 1 transmission s globally can be attributed to the cumulative effect of stigma. 77

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $% Many HIV positive women do not disclose their HIV status to their partners, family and friends which creates potent ial barriers to preventing perpetual sexual transmission to partners, as well as gaining appropriate care in reduc ing vertical HIV 1 transmission via breastfeeding. For many HIV positive women there are several reasons why they may not want to disclose th eir HIV status, and several reasons why they do. Looking specifically at a qualitative study involving 239 recently diagnosed HIV positive pregnant women in Tshwane, South Africa, about 59% of the women in the study disclosed their HIV status to at least one person other than a healthcare provider, while 41% had not done so 7 6 The most common reason women decided to disclose their HIV status specifically to a partner was to inform them of infection risk, 30% decided to do so because a sense of responsibility or obligation because of the relationship. 7 6 T he most recurrent reason to disclose HIV status to parents (52.5%), other relatives and family (59.2%), and friends (82.9%) was because the women in the study though t of these relationships as supportive and trusting. 7 6 Of the women who disclosed to their parents, many felt they needed to do so because they owed their parents the truth, and others disclosed to explain their behavior, illn ess and future death, "I wanted them to know what killed me and asked them to look after my children when I am dead." 7 6 Although there are reasons women disclose their HIV status to friends, family, and partners, many women make the challenging decision n ot to disclose their HIV status One of the most common reasons for non disclos ure to partners in this specific South African population can be attributed to fear. Of 151 women, 31.8% did not want to disclose their HIV status because they were fear ful of abandonment, blame/anger, violence, emotional abuse, and discrimination from their partners 7 6 As an example, one women in the study states, "I do not know how to tell

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $& him [partner] He often says he would kill me if I told him that I'm infected becaus e he does not have HIV." 7 6 A large proportion of these women (27.8%) did not want to disclose because they were not emotionally ready or were waiting for either the delivery of the baby, their partner's test results, or wanted to discuss the issue in pe rson. 7 6 O nly 2.6% intended not to tell their partner at all The women in this study tended to be protective of their parents, "My mother is sick. She had a stroke. I can't tell her because it will affect her health.", approximately 22% of 261 participant s, felt similarly. 7 6 Additional reasons for non disclosure to parents included fear (16.1%) mostly in the context of emotional abuse and discrimination. 76 Overall, most women in the study were unaware of effective ways to disclose their HIV positive stat us to others One common trend among this study population was that fear was a prominent indicator for lack of disclosure. 76 When women did disclose their HIV status, only 11.9% of their partners were supportive, while 30.5% of partners were in denial or disbelief, or shock (14.6%). 7 6 Roughly 36.7% of parents were supportive of their daughters' disclosure, however, 36.7% were saddened, hurt and fearful for their child. 7 6 Of the 173 HIV positive pregnant women who did di sclose their HIV status, 20.2% experienced some kind of adverse consequence. The most frequent adverse reaction was feeling upset by negative feedback from people they disclosed to A small number of women experienced serious negative consequences includin g being abandoned by their partner, physically hurt, or threatened with death. 7 6 HIV disclosure has risks and benefits associated, although, involuntary secondary disclosure can lead to negative experiences as well For a variety of mothers who disclose they

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $' are driven by the desire to ensure adequate infant care and avoid vertical HIV 1 transmission. Primary disclosures, of which the HIV positive mother discloses to family, a partner, or friends, are usually constructive. C onversely, a breach in confidentiality leading to involuntary secondary disclosures usually result in rejection, stigmatization and the withholding of financial support from partners or partners' families 7 6 Various social factors in the context of disclosure patterns greatly impact this subset of women. Disclosure can be shaped by social norms, media influence, political environment, household composition and other social networks. 7 6 These factors can restrict disclosure or alternatively provide a safe place to disclose HIV status. Media plays a sig nificant role in mothers' disclosure With South Africa having one of the highest rates of HIV/AID S, the South African government's management of the epidemic has received regular coverage on radio, television, and other media form s. 7 8 This may facilitate a mothers' disclosure by non direct means. In the qualitative study, HIV disclosure in the Context of Vertical Transmission: HIV Positive Mothers in Johannesburg, South Africa M y sister used to dislike people [infected] with HIV. We were listening to this radio program [about people living with HIV] and I said I didn't like the way she was talking about the people they were interviewing. I said, Don't speak badly about these people. You yourself don't know where you stand [yo u yourself could be infected]. Some of us have had to face this [issue of living with HIV] already.' I think she realized after that [that I am HIV positive]." 7 8 By vo luntarily disclosing by means of proxy, this mother did not need to have a discussion ab out her HIV status. She feared that if she discussed it head on it could lead to issues she did not want

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $( to pursue, such as death or blame for infection. 7 8 There are many mothers in the same situation who prefer to disclose voluntarily by way of the media There can be consequences from instances of involuntary disclosure of HIV status Most women included in the previous study described negative consequences (67.6%) which included emotional rejection, ostracism, and withdrawal of financial and other form s of material support. 7 8 Some women reported a strengthened bond between her and her partner, although, 27% described their partners struggle in coming to terms with their HIV status and 13.8% had deserted them or cut off financial support 7 8 Several mothers in the study stated their family member s seemed beyond responsive termed over care'. This term of over care' delineates the family member(s) providing close attention to the infected individual, causing the person to feel self conscious trapped and isolated. 7 8 As said by a twenty nine year old mother, [My husband's family] started separating out my things from the rest...They would lay everything out for me, saying they wanted to make sure I had everything [I needed]. I had my own pla tes and cups and they would say Here use this. Just use it and wash it right away. They tried to be polite and caring but I could see it [my HIV status] made them uncomfortable...On my side [of the family] they are too [heavy emphasis] supportive. They a re too concerned. They are always asking me Are you okay? Are you getting sick?' So now I have started feeling guilty...they are too focused on me. [I feel as though] my life is no longer [my own]." 7 8 Although the family is trying to be attentive to the c are of this mother, over care' may cause severe negative psychological affects, and diminish the relationship in the long run. The majority of the mothers in this study voluntarily disclosed their HIV status, which contributed to an extremely low 8.7% rat e of vertical transmission by means of breastfeeding avoidance 7 8

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $) Disclosure not only reduces burden for HIV positive mothers, but also empowers them by provi ding a platform to seek out and pr actice appropriate care to reduce vertical HIV 1 transmission Although, for many women disclosing HIV status immediately promotes stigmatization and ostracism in their families, and communities. Avoidance of breastfeeding in many places and cult ur es automatically marks a woman as HIV positive by her family and co mmunity There are a variety of reasons HIV positive mothers choose certain infant feeding modalities Factors of determination may include: cost of infant formula, influence from health workers, influence from relatives, stigma influencing non disclosure of HIV status, and difficulties of maintaining exclusive breastfeeding or exclusive replacement feeding. 7 9 Many HIV positive mothers would prefer to utilize infant formula as an alternative method of infant feeding, although, because of the cost, decide to breastfeed. In addition to the cost of formula feeding, this option would ultimately disclose the mothers' HIV status. A mixed qualitative and quantitative study consisting of interviews and focus groups with 811 Zambian mothers focused on infant feeding decisions, disclosure and stigmatization V arious comments were made regarding the associated stigma and disclosure of HIV status 79 I can buy milk, I can buy formula. Now I do not want to because my neighbor will be asking me, why are you not breastfeeding? And why have you stopped ?' [ breastfeeding ] at 6 months because nowadays most people know that if you stop at 6 months it means you are not okay [ HIV positive ] I feel ashamed that if my friends see me giving milk to the baby they will know [ my status ] so it is better I breastfeed. This is what is happening most of the time to the mothers.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES $* and found to be HIV positive they fail to tell their husbands so in the process of hiding [ the results ] from husbands, you find that the husband has a good job, can even manage to buy milk for the baby but because they want to hide their status from their husband you find that they will be breastfeeding the baby. So such mothers say we are protecting our marriages because if my husband gets to know I will be chased. The stigma associated with replacement feeding and HIV status is prominent This poses risk for any HIV positive mother who chooses to use an alternative method of infant feeding in order to protect her child from HIV/AIDS Women who do not breastfeed are at great risk of being stigmatized, they risk ostracism from their partner, family and community, while simultaneously increasing risk of depression and low quality of life. 79 In order to decrease stigma associated with HIV and replacement feeding, be tter education and pr omotion of breastfeeding in many circumstances will empower mothers to mak e appropriate and healthful feeding choices for their infants. Additionally, health workers should be educated on the respective policy of their country and the feeding methods which are suitable for the at risk population. Overall, stigma plays a noticeable role when mothers are deciding whether or not to breastfeed their child. If mothers do not breastfeed and choose to utilize alternative methods of feeding, th ey have an increased risk of stigmatization among other negative outcomes V. Factors Which May Effect Vertical HIV 1 Transmission For many HIV positive mothers, breastfeeding is the only affordable, accessible, and safe method for infant feeding If an HIV positive mother chooses to breastfeed her infant there are considerations to take into account. Maternal nutrition and health status influence HIV 1 transmission via breastfeeding. Various comorbidities have been shown to increase vertical HIV

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %+ 1 transmission via breastfeeding, and well as c ertain micronutrients when supplemented to HIV positive pregnant and lactating women According to the review article, The Role of Co Infections in Mother to Child Transmission of HIV there a re a variety of com orbidities (co infections) which affect the mechanisms of mother to child transmission of HIV 1 in utero, at delivery and through breastfeeding. 80 Considering comorbidities that affect transmission rates via breastfeeding, there are many. A comorbidity of m astitis, increases mother to child HIV 1 transmission by increasing viral load in breastmilk. Breastmilk contains cell free HIV inhibitors, because of the milk blood barrier, concentrations of HIV are typically 10 100 times lower in breastmilk than in p lasma, however infection and inflammation of breast tissue can increase viral load in breastmilk significantly 8 1 The increase in breastmilk viral load increases risk of postnatal mother to child transmission. Roughly 10% 33% of women experience mastitis, typically during early breastfeeding, mixed feeding and during the weening stages of lactataion. 80 Clinical mastitis and subclinical mastitis differ and are classified based on the degree of inflammation in the mammary gland s Clinical mastitis may be cha racterized by cracked nipples sores, pain, swelling, and redness Cracked nipples and s ores frequently bleed during breastfeeding, therefore increasing the infant's exposure to plasma HIV of which viral cells are higher than in breastmilk alone 8 2 Similarly, subclinical mastitis is characterized by an elevated leukocyte count, elevated sodium or elevated sodium/potassium ratio and is much more common 80 Both clinical and subclinical mastitis can alter the cellular tight junctions which regulate brea st epithelial permeability. 80 Research has suggested that up to 50% of postnatal HIV 1 transmission s can be

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %" attributed to some form of subclinical mastitis. 8 3 If an HIV positive mother does develop mastitis or an abscesses, she must express milk from the affected side frequently and discard it and continue feeding fro m the unaffected side. 84 In sub Saharan Africa, and many other places worldwide it is common practice for mothers to pre masticate food given to infants during the weaning period, or if not exclusively breastfeeding. 8 5 There have been various studies that not e infants becoming infected with HIV who were previously HIV negative, yet had only been given food that was pre masticated by an HIV positive mother or caregiver. 80 In these cases, the H IV positive mothers or caregivers had evidence of bleeding gums: gingivitis. It is contraindicated for HIV positive mothers and caregivers to pre masticate food with poor dentition as it can increase d risk of transmission If an infant has oral thrush, or al sores, or bleeding in the oral cavity, risk of HIV 1 transmission via breastfeeding increases. 8 6 HIV progression has been associated with low serum concentrations of micronutrients, intestinal abnormalities and a continuous inflammatory state through o ut the body. 8 7 Many micronutrient deficiencies are apparent within underdeveloped countries and HIV infected populations Micronutrient deficiencies can impair immune response, and is associated with accelerated disease progression in the HIV/AIDS population 8 8 Current research suggests that adequate vitamins B, C, E and folic acid ( an additional B vitamin ) have been shown to delay the progression of HIV and reduce mother to child transmission 8 7 B vitamins are essential in the hum an body and immune system. Riboflavin (vitamin B 2 ) deficiency decreases the humoral antibody response, vitamin B 6 deficiency reduces maturation of lymphocytes, and vitamin B 12 deficiency impairs the function of neutrophils. 8 9 People living with HIV could i mprove survival with increased intake of B vitamins overall. In various studies, high serum levels of vitamin B 12

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %# B 1 B 2 B 6 and niacin were all associated with improved survival and delayed HIV progression. 90 9 1 The overall survival time of patients using vitamin B supplements w ere significantly longer than of those not supplementing with B vitamins in HIV positive population s 90 According to various studies, ascorbic acid ( vitamin C ) and tocopherol (vitamin E ) were found to be lower among people living with HIV. 8 7 Lower levels of vitamin s C and E are related to higher levels of oxidative stress, which in turn, may lead to increased viral replication therefore increasing viral load 9 2 Multivitamin supplements with vitamin C and E delay the progre ssion of HIV by increasi ng CD4 and CD8 cell counts while lowering viral load. 92 93 The role of vitamin D is not well studied in HIV progression, although there have been few studies regarding vitamin D status and maternal infant morbidity and mo rtality as well as vitamin D association and mother to child HIV 1 transmission. 8 7 One study found that children born to mothers with low vitamin D levels had a 64% great er risk of dying during follow up and an overall 46% greater risk of contracting HIV. 9 4 Conversely, in another study with a trial of 367 tuberculosis patients containing a subgroup of 135 HIV positive patients located in Guinea Bissau the impact of vitamin D supplementation every four months over a twelve month period on mortality and the c linical severity of tuberculosis was tested. 95 The study found that vitamin D did not appear to have an impact on mortality in both the complete group and the HIV positive subgroup. 9 5 There is limited, or insufficient evidence to recommended vitamin D use among people living with HIV unless already deficient. Selenium has been suggested to be a key nutrient for people living with HIV. Lower serum concentrations of selenium in both adults and children infected with HIV have been linked to increased viral lo ad, and mortality. 9 6 The role of selenium in immunity and antioxidant

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %$ defense may be the underlying mechanism of an increased HIV progression with lower serum levels. 9 7 Observational findings prompted various clinical trials that assessed whether selenium supplementation could have an impact on HIV viral load, CD4 counts, or HIV progression. In a randomized control study with 186 HIV positive men and women, who were supplemented with 200 g of selenium, found that the selenium did not affect CD4 count leve ls or viral load after two years follow up. 9 8 Although, a smaller proportion (25%) among the selenium group experienced a substantial decline in CD4 count, when compared to the placebo group (46%). 9 8 Additionally, the relative risk of being admitted to a hospital was 2.4 times lower among the selenium supplemented group compared to the placebo group. 9 8 I n a randomized control trial, 262 HIV infected patients were supplemented for nine months with 200 g of selenium. 9 9 This resulted in an increase in CD4 counts, and a decrease in viral load. 9 9 Specifically looking at the impact of seleni um supplementation on HIV positive mother and child mortality, a randomized controlled study was conducted with 913 pregnant HIV positive women in Tanzania. 100 Daily 200 g selenium supplementation until six months postpartum did not affect CD4 count, vira l load, or overall maternal and infant mortality. 100 However, six weeks after delivery, a reduction of 57% morbidity and mortality in the selenium supplemental child population was found. 100 Although selenium is important for maternal and child health, overall, there is not enough evidence to support providing selenium supplements to HIV positive persons who a re not deficient or are already receiving a high dose multivitamin. 8 7 In contrast excessive supplementation of vitamin A, iron, and zinc have been associated with adverse health effects and caution is warranted for their use in HIV positive maternal po pulaitons. 8 7 Vitamin A plays an important role in immune function, and is essential for maternal and infant health. According to the WHO, supplementation of vitamin A and/or

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %% carotene to HIV positive women during pregnancy may reduce the risk of mother to child transmission of HIV. 10 1 However various studies have challenged that claim, and in contrast prove an increase of viral loa d in breastmilk with high dose supplementation of vitamin A and/or carotene therefore increasing risk of mother to child HIV 1 transmission via breastfeeding. According to a Randomized Trial of Vitamin Supplements in Relation to Vertical Transmission of HIV 1 in Tanzania a total of 1,078 HIV positive women were given either vitamin A and carotene, or a multivitamin excluding vitamin A and carotene starting at 20 weeks' gesta tion through out lactation. 10 2 According to the study, vitamin A and carotene increased the risk of vertical HIV 1 transmission while the multivitamin excluding vit amin A and carotene had no effect on the total risk of transmission. 10 2 In the study Effect of Vitamin Supplements on HIV Shedding in Breast Milk 594 Tanzanian HIV infected women received either a multivitamin, vitamin A and carotene, a multivitamin including vitamin A and carotene, or a placebo. 10 3 Women received these supplement s in a 2 x 2 factorial fashion during pregnancy and throughout the first two years postpartum. 10 3 Results concluded that vitamin A and carotene increased viral load in breast milk thus increasing risk of transmission 10 3 In some instanc es, supplementation of vitamin A and/or carotene for HIV positive women who are breastfeeding may carry additional risks, therefore contributing to mother to child HIV 1 transmission via breastfeeding. According to the article, Vitamin Su pplementation Increases Risk of Subclinical Mastitis in HIV Infected Women 674 women produced 1,642 breast milk samples for analysis of Na:K (sodium: potassium) ratio to determine risk of subclinical mastitis. 10 4 Women were placed on a multivitamin excluding vitamin A or carotene, a multivitamin including vitamin A and carotene, only vitamin A and carotene, or

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %& a placebo with breastmilk sampling e very three months. 10 4 Results found that supplementation of vitamin A and carotene increased the risk of severe subclinical mastitis by 45%. 10 4 The increased risk of subclinical mastitis directly correlates to an increase in mother to child HIV 1 transmission via breastfeeding. The literature regarding vi tamin A supplementation and mother to child HIV 1 transmission via breastfeeding is largely i n need of more research Additional research will strive to determine whether or not mothers who are HIV positive and breastfeeding should be supplemented with vitamin A and / or carotene, at what tim es during pregnancy and/or lactation and at what regimen s. Overall, women who are deficient regarding general micronutrient status might reduce transmission rates via breastfeeding if placed on a multivitamin in order to re plete and maintain a ppropriate nutrition status, but it may not be appropriate to megados e with vitamin A and/or carotene. Iron deficiency is the most common nutritional deficiency in the world while t he majority of people suffering are wom en. 17 In the HIV /AIDS population, anemia is prevalent and is associated with increased mortality HIV progression and a more rapid (50%) decline i n CD4 counts leading to an early AIDS related death 10 5 However, iron deficiency anemia does not increase risk of vertical HIV 1 transmission via breastfeeding. I n the study, Postnatal Anemia and Iron Defici ency in HIV Infected Women and the Health and Survival of Their Children maternal anemia was not significantly associated with an increased risk of mother to chi ld HIV 1 infection postnatally. 10 6 Although i t has been documented that very low maternal iron stores contribute to diminished child health and survival by reducing infant iron stores, and impairing cellular immunity during breastfeeding. 10 6 ,107

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %' Proper screening for low iron stores and iron deficiency anemia in women particularly in the HIV p ositive population, will increase survival rates considerably Zinc deficiency amongst people living with HIV may account for an improper maturation of CD4 cells mediated through low levels of the zinc dependent hormone, thymuline. This may lead to a less effective immune response and a higher susceptibility to opport unistic infections further perpetuating HIV to AIDS while increasing risk of morbidity and mortality. 10 8 Several studi es have been conducted with zinc supplementation to HIV positive populations and may be harmful, rather than helpful In reference to, Trial of Zinc Supplements in Relation to Pregnancy Outcomes, Hematologic Indicators and T Cell Counts Among HIV 1 Infected Women in Tanzania 400 HIV positive women in Tanzania were assigned to receive a daily oral dose of 25mg of zinc or a placebo startin g between 12 and 27 weeks' gestation 10 9 The study found that zinc had no effect on CD4, CD8, or CD3 coun ts during the follow up period, but had negative effects on hemoglobin concentrations. 10 9 In a similar study, Zinc Supplementation to HIV 1 Infected P regnant Women: Effects on Maternal Anthropometry, Viral Load, and Early Mother to Child Transmission 400 HIV positive pregnant women who had never been treated with antiretroviral therapy drugs received a multivitamin (vitamins B, C, E, and folic acid). 1 1 0 The women were randomized to receive, in addition, either a placebo or a 25 mg daily dosage of zinc until 6 weeks after delivery. 1 10 Results of the study showed no differences in HIV transmission, CD4 or CD8 counts, and viral load. However, zinc suppleme ntation was inversely associated with hemoglobin levels, and was then related to a threefold increase in the probability of maternal wasting. 1 10

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %( Further research is warranted to assess whether there is a potential role for zinc supplementation among HIV positive persons treated w ith antiretroviral therapy drugs and those who have never been on treatment However it may not be appropriate for pregnant HIV positive women to be supplemented with zinc, as it may lead to increased wasting Overall, HIV posi tive women who are deficient regarding general micronutrient status m ay reduce transmission rates via breastfeeding if placed on a multivitamin regimen in order to re plete and maintain appropriate nutrition status However it may not be appropr iate to meg adose with vitamin A, and/or carotene, zinc or iron Without proper access to health care and breastfeeding education, women are likely to transmit HIV to their infants when comorbidities arise and if supplementation is not appropriate Maternal health status can greatly influence rates of inc rease d or decrease d HIV 1 transmission via breastfeeding. Global Health Policy I. Developing Nations Health policy differs at the local, national and global level. With differing circumstances across the world, global health policy is crafted and determined by issue s which affect communit ies and the majority of at risk populations HIV/AIDS has existed for years, dating back to the 1950's, later reaching the United S tates in the mid to late 1970's. 11 1 In 1983, scientists discovered the virus that causes HIV and AIDS only thirty four years ago. 11 1 HIV/AIDS is a relatively new disease which has infected and killed millions. V arious policies at the national and global level have been established and revised aimed at thwarting and reducing the instance of HIV/AIDS Once researchers and scientists discovered that HIV can be transmitted vertically, programs have been implemented to prevent moth er to child HIV 1 transmission. Although,

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %) there is no single means of prevention, therefore, global and national organizations have changed recommendations and policies repeatedly over the last thirty years. When recommendations and policy are revised, ne w research and information alters current recommendations providing more culturally appropriate and evidence based material. Various topics can change recommendation and policy which may include challenges with implementation, as well as coverage and quali ty of interventions being disturbingly low and inaccurate. 112 Furthermore, insufficient or non existent infant feeding counseling provided by health workers leads to inappropriate feeding choice s by both HIV infected and HIV uninfected women 112 Poor counseling recommendations on breastfeeding consequently caus e sharp increases of infant death from diarrheal episodes and pneumonia 11 2 Therefore, problematic issues have to be considered in order to provide recommendations that are evidence based a nd appropriate for the at risk population. Most notably the World Health Organization (WHO) has been releasing and reviewing recommendations for HIV positive mothers since 2000 aimed at dec reas ing and prevent ing vertical HIV 1 transmission H owever the WHO's recomme ndations have drastically changed over the last 17 years I n 2006 the WHO recommended exclusive breastfeeding for HIV infected women for the first 6 months of life unless replacement feeding was acceptable, feasible, affordable, sustaina ble, and safe for them and their infants before that time. 11 2 Additionally, when replacement feeding was acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV infected women was recommended. 11 2 Additionally, the 2006 WHO guidelines recommended lifelong antiretroviral therapy drugs for pregnant women, based on specific eligibility criteria. Lifelong antiretroviral therapy could be started for pregnant women

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES %* who had a CD4 count below 200 cells/mm 3 which i s generally the stage of the disease in which the immune system is no longer able to effectively prevent opportunistic infections. 112 Among the guidelines and recommendations for HIV positive breastfeeding, programmatic implications for monitoring and evalu ation, as well as implications for conflict and emergency settings also exist. In 2010, recommendations from the WHO changed again stating that women known to b e HIV infected (and whose infants were HIV uninfected or of unknown HIV s t atus) should exclusive ly breastfeed their infants for the first 6 months of life, int roducing appropriate complementary food thereafter, and continue brea stfeeding for the first 2 years of life. 11 3 The WHO 2010 recommendations also provided national governments the option of recommending either (1) exclusive breastfeeding and antiretrovi ral therapy drugs for women who meet eligibility criteria, or (2) recommend avoidance of all breastfeeding, which would most likely give the infant a greater change of HIV free survival. 11 3 T h e 2010 WHO guidelines promote starting lifelong antiretroviral therapy drugs for all HIV positive pregnant women with severe or advanced clinical disease (stage 3 or 4), or with a CD4 count at or below 350 cells/mm 3 regardless of symptoms. 11 3 As soon as t he eligibility criteria are met for pregnant and non pregnant HIV positive women, antiretroviral therapy drugs could be initiated. 11 3 In 2015 W HO recommendations changed once more Currently, HIV positive mothers should breastfeed for at least 12 months and may continue breastfeeding for up to 24 months or longer while being fully supported for antiretroviral therapy drug adherence. 11 4 The next time the WHO guidelines and recommendations regarding prevention of mother to child HIV 1 transmission will be updated is in 2019. 11 4 Countries are encouraged to hold discussions to

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &+ inform decision making on the use and introduction of the 2015 WHO recommendations into national programs. 11 4 For the first time, current WHO guidelines recommend two interventions involving antiretroviral therapy drugs : (1) providing lifelong antiretroviral therapy drugs to all pregnant and breastfeeding women living with HIV regardless of CD4 count or clinical stage, and (2) prov iding antiretroviral therapy drugs for HIV positive pregnant and breastfeeding women during the mother to child transmission risk period and then continuing lifelong antiretroviral therapy drugs for those women eligible for treatment for their own health. 11 5 This allows the child to benefit from breastfeeding with little risk of becoming infected with HIV However, attaining and compliance of taking the recommended antiretroviral therapy drugs may not be as simple as the current recommendation suggests. The combination of exclusive breastfeeding and antiretroviral therapy drugs can significantly reduce the risk of vertical HIV 1 transm ission via breastfeeding. 14 The WHO led Kesho Bora study found that giving HIV positive mothers a combination of antiretr oviral therapy during pregnancy, delivery and breastfeeding reduced the risk of HIV transmission to infants by 42%. 1 4 The breastfeeding Antiretroviral and N utrition study in Malawi also showed a risk of HIV transmission reduced to just 1.8% for infants giv en the antiretroviral drug N evirapine daily while bre astfeeding for six months. 1 4 A simple method of trying to reduce transmission rates of HIV through breastfeeding would be t o offer free infant formula to the HIV positive maternal population Although distribution of free infant formula seems to encourage mixed breastfeeding, consequently increasing rates of HIV transmission and infant death 8 4 The greatest declines in breastfeeding

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &" have taken place in countries where infant formula has been distribute d at no cost, South Africa being a prime example. In the early 2000's, South Africa had some of the highest rates of HIV prevalence in the world. In 2001, in order to prevent mother to child HIV 1 transmission infant formula was distributed by national a nd local authorities in addition to local nongovernmental organizations at no cost for all infants up to 6 months of age. 11 6 The free formula was provided at all public health facilities, a lthough, the policy had unforeseen consequence s w omen who were no t HIV positive turned to infant formula as well. 11 6 This initiative inevitabl y undermined breastfeeding, as a result, breastfeeding rates plummeted to roughly 1.5% nationwide in 2003. 11 6 Infant death subsequently skyrocketed, and South Africa was left with a challenging decision on how to fix the issue. In 2011, South Africa passed the Tshwane Declaration aimed at improving low breastfeeding rates while increasing infant survival. The po licy mandates that public health facilities stop providing infant formula to all new mothers, whil e promoting milk banks, and increasing counseling services about the importance of breastfeeding. In 2016, exclusive breastfeeding rates for the first 3.5 mon ths postpartum were at approximately 40%, although, rates decrease to 8% at six months. 11 7 Significant increases in breastfeeding over the last 5 years, points to success with South Africa's newest policy implementation. HIV positive mothers are provided free antiretroviral medication, and are forced to exclusively breastfeed if they cannot aff ord infant formula as none will be provided free of charge Exclusive breastfeeding, coupled with accessible antiretroviral therapy drugs, has decreased mother to child HIV 1 transmission, while significantly increased exclusive breastfeeding rate s and dec reasing infant death

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &# However, the Tshwane Declaration poses an issue for mothers who need to return to work or leave their child in the care of someone else for whatever reason. 11 8 Now these mothe rs are faced with the issue of finding alternative feeding methods for their infant s or trying to express breastmilk in the workplace Certain organizations and places of work may not be suitable for pumping or expressing breastmilk for an infant Workplaces may also lack appropriate storage for the expressed breastmilk during work hours Additionally, women may be comm uting long hours to work and cannot store expressed breastmilk appropriately on their way back home. 11 6 It has been documented that a ntiretroviral therapy drugs can drastically reduce rates o f mother to child HIV 1 transmissio n. In developed countries, providing antiretroviral therapy drugs for mother and infant is standard of care decreasing mother to child HIV 1 transmission rates to below 2%. 11 In developed countries such as the United States breastfeeding while HIV positive is contraindicated, even on antiretroviral therapy drugs. As said by the American Academy of Pediatrics, "In the industrialized world, it is not recommended that HIV positive mothers breastfeed." 13 The position statement does take into account developing countries and HIV positive mother's breastfeeding, "However, in the developing world, where mortality is increased in non breastfeeding infants from a com bination of malnutrition and infectious diseases, breastfeeding may outweigh the risk of the acquiring HIV infection from human milk Infants in areas with endemic HIV who are exclusively breastfed for the first 3 months are at a lower risk of acquiri ng HIV infection than are those who received a mixed diet of human milk and other foods and/or commercial infant formula Recent studies document that

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &$ combining exclusive breastfeeding for 6 months with 6 months of antiretroviral therapy significantly decreases the postnatal acquisition of HIV 1." 13 The American Academy of Pediatrics also states, c ontinued ingestion of illicit drugs or alcohol, and underlying conditions, such as HIV infection, are not compatible with breastfeeding. Patients als o require ongoing psychosocial support to maintain abstinence." 13 T he CDC has a much more declarative stance on the issue, It is not advised to breastfeed if the infant's mother has been infected with HIV, or is taking antiretroviral medication." 1 2 1 Although the WHO has provide d suitable guidelines for HIV positive breastfeeding for women of developing countries, in developed countries such as the United States, policy differs. T he American Academy of Pediatrics takes into account women of developin g countries however, they do not denote anything about cultural stigmatization, cultural barriers, or superstition issues that are prominent many cultures and countries When women of developing countries seek asylum, immigrate, or become refugees in the United States, the question of whether or not HIV positive women are receiving care based on policy alone or in conjunction with cultural health belief s dev elops From 1993 until January, 2010 positive HIV status was considered a ground of inadmissibility in the United States HIV positive foreign nationals would be denied short term visas or applications for lawful permanent residence based s olely on HIV status. 1 2 0 Various countries worldwide have similar, strict, regulations on entry, stay and residence for people living with HIV. Countries that currently have an entry ban fo r people living with HIV/AIDS are as follows: Brunei, Equatorial Guinea, Iran, Iraq, Jordan, Papua New Guinea, Qatar, Russia, Singapore, Solomon Islands, Sudan, the United Arab Emirat es, and Yemen. 1 2 1 C ountries that

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &% have travel and residence bans in the context of positive HIV/AIDS status have considerably smaller prevalence of people living with HIV/AIDS compared to many other parts of the world 1 2 2 After a twenty year HIV travel and immigration ban in the United States, on January 4, 2010 it came to an end. Being HIV positive is no longer an auto matic ground of inadmissiblity 1 2 0 Doctors no longer perform an HIV assay as part of the medical examination, although, the doctor could ask questions about overall health in which HIV status could come up. When The Department of Health and Human Services (HHS) final regulations went into effect, it removed HIV from a list of communicable diseases of public health significance' A lthough so me doctors may continue to use the old form, they are now instructed not to test for HIV. 1 2 0 Many women and children seek asylum and/or refugee in the United States because of the stigmas and hardships associated with positive HIV status in their own country. During 2007 2008, approximately 14% of the incoming refugees to the United States arrive d fro m countries with HIV prevalence >5%. 1 2 3 Since the 2010 ban on travel restrictions for persons living with HIV, assumptions can be made that a significant increase of HIV positive people have, and are, immigrating and seeking refugee status in the Unite d States annually. The CDC outlines post arrival screening methods in order to best serve the health of people living with HIV who are moving to the United States. 12 3 Current CDC guidelines for the United States recommends HIV screenings in health care setting s for all refugees aged 13 64 not to deny entry, but as a preventative measure 1 2 3 For refugees who may be considered in the window period' when they arrive, repeat screening 3 6 months following resettlement is recommended. 1 2 3 The window period of HIV varies from person to person. Most HIV tests are antibody tests, although, the body takes time to produce

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES && enough antibodies for an HIV test to detect the disease. 12 4 The soonest an antibody test will detect infection is at three weeks post infecti on. 12 4 However, most people will develop d etectable antibodies closer to 4 12 weeks post infection. 12 4 Source: http://i base.info/guides/testing/what is the window period The CDC guidelines have special pediatric considerations regarding HIV and testing Children <13 years of age should be screened unless the mother of the child can confirm HIV negative status. In most situations, complete risk information will not be available, therefore, most children <13 years of age should be screened. 1 2 3 Children who are <18 months of age who initially test positive for HIV antibodies, should receive further testing with DNA or RNA assays. Results of an initial positive antibody test in this age group can be unreliable, as they may detect persistent mater nal antibod ies 1 2 3 Additionally, all children born to, or breastfed by an HIV positive mother should receive antiretroviral therapy beginning >6 weeks of age until confirmed to be uninfected. 1 2 3 In the pregnant refugee population, all women should undergo routine HIV screening as part of their post arrival and prenatal medical screening and care. 1 2 3 During initial intake assessments, disclosure of HIV status may not be forthcoming. It is imperative that the screening and assessments in this population is d one with dignity, and in a supportive manner. Refugees represent a population vulnerable to HIV infection and disease, therefore HIV screening should

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &' be offered to all refugees, immigrants, and persons seeking asylum resettling in the United States. 1 2 3 Overall, global and national health policy are ever changing. Health policy can be seen as an umbrella, covering most, but not all. Although health policy aids the majority in need, s ome policies may not be appropriate for certain populations. With an incr ease in research, and continued information in the context of vertical HIV 1 transmission, policy will constantly change until the epidemic is reduced. With global health policy shifts, compliance with recommendations and policy is passive G lobal health p olicy then becomes essentially ineffective in populations who need it most. !!" #$%&'()*+,.(/0 1'$2)'-3,)'/0-4$'(+5 Policy shifts can impact people at all levels. T he ultimate goal of global health policy is to provide evidenced based recommendations to the HIV positive maternal infant dyad, while taking into consideration cultural differences and barriers. Global health policy is obligated to promote recommendations enabling maternal and infant health However, it is difficult to provide recommendations on a glo bal level when research on the subject is still being done HIV/AIDS is such a new' disease, that recommendations over the last twenty years have changed dramatically attempting to prevent and reduce mother to child HIV 1 transmission. Recommendatio n shifts from the WHO negatively impact HIV positive mothers who have to make the difficult decision to either initiate or avoid breastfeeding as well as the health workers counseling and proving advice to this population These various global health policy shifts are confusing health workers and HIV positive mothers, to a degree that policy becomes relatively ineffective and complicat es prevention programs

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &( Many countries continue to face shortages of trained health wo rkers. 12 5 Additionally, the effectiveness and efficiency of available personnel is lacking. 12 5 There are c hallenges concerning health workers to keeping prevention programs ongoing and successful Effective programs require more than basic resources, there fore, proper training is dynamic and difficult. 12 6 Health workers may not have up to date information and recommendations in the context of vertical HIV 1 transmission via breastfeeding. 12 6 It is though t that health workers need contextualized, easy to fol low guidelines in order to effectively provide evidence based advice and services. 12 6 Supportive supervision should also be in place to enable health workers to provide a confident service. P rogram managers, counselors and HIV positive pregnant women continue to be confused with shifting global health policy and recommendations Low levels of knowledge and awareness pertaining to infan t feeding options confirms a need for clarity. 12 7 Many c ounselors and health workers either avoid the topic during coun selling sessions, or push women in a particular direction that may not be suitable at an individual level 12 7 As a result, HIV positive women are given inadequate knowledge to mak e appropriate infant feeding choices. 12 7 The social and cultural distance between the producers of the guidelines and the global recipients has generated a sense of helplessness, confusion, guilt and fear among people involved in intervention s with in certain populations 12 8 HIV positive women have b een unable to adhere to the c hanging infant feeding recommendations without emotional stress and fear of harming their infant 12 8 Counselors have reported uncertainty and loss of faith with their work in infant feeding after experiences with large number s of non compliant HIV positive mothers. 12 8 Overall, many health workers are worried that the continual confusion regarding infant feeding has reduced public trust in nursing as a profession. 12 8

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &) The lack of clarity with shifting global health policy promote s mixed feeding methods as confusion rises. HIV positive mothers may be recommended to feed their infant in a certain wa y fro m health workers who are not as knowledgeable about the topic as they should be, or health workers may be referencing old recommend ations, or something false they have heard from a program manager. Confusion increases in b oth the coun selor and HIV positive mother which contribut es to psychological barriers, as well as inappropriate infant feeding me thods Following the release of th e 2015 WHO guidelines, the global organization no longer recommends multiple options for prevention of mother to child HIV 1 transmission, but instead advises that all HIV positive pregnant and breastfeeding women should receive antiretroviral therapy drug s regardless of clinical stage (CD4 count) of disease provided by national governments This approach has since been adopted by most countries with high burden of disease. 1 29 However, t here are numerous issues with implementing this method to reduce and prevent mother to child HIV 1 transmission Common antiretroviral therapy drugs for the HIV positive maternal infant dyad include: Z idovudine ( r etovi r ) and N evirapine (viramune) 1 3 0 With use of Zidovudine serious side effects can arise. Severe bone marrow problems have been reported, especially in patients with advanced HIV infection causing anemia. Additionally, instances of lactic acidosis, as well as severe and sometimes fatal liver problems have also been reported. 1 3 1 Iron deficiency anemia is th e most common deficiency worldwide, and prevalent in the HIV positive female population. 17 Lifetime use of Zidovudine will perpetuate the high rate of anemia in HIV positive women causing increased comorbidities, greater risk of opportunistic infection and subsequently death. Additionally, 51.4% of people taking this drug experience nausea, 21.1% anorexia, and 17.2% vomiting 1 3 1

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES &* Severe side effects have been reported with the use of N evirapine as well. F atal liver problems have occurred in patients, especially during the first 18 weeks of th erapy, but may occur at any time during treatment. 1 3 2 Pregnant women, and women with a CD4 count higher than 250 mm 3 are at greatest risk. Major and common side effects of N evir apine include : diarrhea, nausea, and v omiting, pl us sores, ulcers, or white spots in the mouth or on the lips. 1 3 1 Up to 10% of people on N evirapine experience nausea and vomiting and up to 5% experience diarrhea. 1 3 2 Almost 52% of people who take Zidovudine experience nausea, while 20% of people experience vomiting. 13 1 1 3 2 Additionally, 10% of people taking N evirapine experienc e vomiting, with 10% experiencing diarrhea 13 3 1 3 4 The combination of taking both drugs increases n ausea and diarrhea which can in turn decrease therapeutic le vels of the antiretroviral therapy drug s Sub therapeutic drug levels cause decreas ed medication effectiveness that impairs the efficiency of the d r ugs leading to instances of vertical HIV 1 transmission via breastfeeding even while taking the prescribed medication 1 3 3 Additionally, side effects with medication were the most commonly reported barriers to antiretroviral therapy drug adherence. 30 As the disease progresses into the symptomatic stage of HIV common symptoms in crease and become more prominent. N otable issue s relating to untreated HIV progression are the instance s of chronic diarrhea weight loss, in addition to mouth and skin problems. 13 4 The 2015 WHO recommendations suggest providing antiretroviral therapy drugs at no cost to HIV positive mothers without eligibility requirements. I f an HIV positive pregnant women is already in the third stage of HIV, chronic diarrhea is prominent and antiretroviral therapy drugs would perpe tuate that issue which could decrease therapeutic levels of the drugs provided 13 1 13 2 ,13 5

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '+ Assumptions can be made that a majority of HIV positive pregnant women are also drinking unclean water thereby increasing risk of diarrheal episodes from waterborn e pathogens Therapeutic levels of antiretroviral therapy drugs are reduced with i n stances of diarrhea l episodes from unclean water, disease progression, and side effects of antiretroviral therapy drugs 1 3 5 In order to increase sub therap e utic levels to effective ranges, additional antiretroviral medication is warranted and blood serum levels should be tested frequently. The above limitations will test the sustainability of recommended antiretroviral therapy drugs for all HIV positive women in upcoming years Although there are downsides to taking antiretroviral therapy drugs, i n the context of saving lives, they are essential Since 1995, an estimated 1.6 million new HIV infections among children have been averted due to the provision of antiretroviral medication. 77 Antiretroviral therapy drugs do not cure HIV or AIDS, but t he disease is treated using a combination of medications a imed at suppressing the amount of the HIV virus in the body. 13 6 Antiretroviral therapy drugs prevent HIV from multiplying while giving your body a chance to recover and fight off infe ctions and cancers caused by the disease 13 6 Additionally, the use of antiretroviral therapy dugs decrease risk of transmitting HIV to o thers as well as prolong life expectancy of the infected individual 13 6 In 2005, only seven developing countries provided free antiretroviral therapy drugs to at risk populations : Botswana, Brazil, Ethiopia, The United Republic of Tanzania, Thailand, Sene gal and Zambia 30 The countries decided to abolish user fees for HIV treatment in order to increase adherence and overall public health. 30 The importance of no cost treatment is significant because cost of any amount prevents people from adhering to antire troviral therapy. 30 Throughout the years, as access to antiretroviral therapy drugs increased, many populations were

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '" able to effectively utilize health care services to prolong their lives and reduce risk of transmission However, because of prominent barriers, only about half of women who were eligible fo r antiretroviral therapy drugs were accessing treatment 13 7 W hen the WHO put out the 2015 recommendations concern ing prevention of mother to child HIV 1 transmission and antiretroviral therapy treat ment priorities included: increasing the demand for antiretroviral therapy, investment in antiretroviral t herapy programs, and effective deliver y of antiretroviral therapy services. 30 African governments are among leaders in global efforts to mobilize resources for antiretroviral therapy ; domestic contributions account for roughly half of all spending on HIV treatment and care across sub Saharan Africa. 1 3 8 Notable countries including Bo tswana, Angola and South Africa finance 80% of antiretroviral therap y drugs through public and private sources. 1 3 8 Several countries have been exploring innovative financial strategies in order to diversify funding and generate renewable sources of funding for HIV programs. 1 3 8 As an example, in C™te d'Ivoire, tobacco and a lcohol are being taxed to generate funds for HIV and AIDS response. 1 3 8 National priorities for HIV spending is important for the effectiveness of HIV response. The magnitude of costs is a serious challenge for many countries 83% of domestic financing go es to care and treatment in sub Saharan Africa South Africa alone distributes a sizable amount of antiretroviral therapy drugs, owing to increased prevalence of the disease. 138 Although there is significant financial support from domestic contributions, e xternal donors (The United States, and other developed countries) supplement HIV prevention programs which include antiretroviral therapy drugs. 31, 1 3 8 The cost of antiretroviral therapy drugs fo r all persons infected with HIV is grossly high, which remains concerning for sustainability efforts for financing HIV/AIDS care and treatment. 1 3 8

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '# The United State s alone has provided funding to address the global HIV epidemic starting in 1986. 1 39 Total funding has increased since initiation, although, since about 2010, funding from the United States has r emained relatively flat. 1 39 Of the $6.6 billion (USD) spent each year on global HIV/AIDS efforts by the United States $5.2 billion (USD) is allo cated to bilateral programs, and $1.35 billion (USD) is distributed as a U.S. contribution to T he Global Fund to R educe AIDS, Tuberculosis and Malaria. 1 39 Source: The Henry J. Kaiser Family Foundation. Global health policy: U.S. federal funding for HIV/AIDS: trends over time. Updated 2016. http:// kff.org/glob al health policy/fact sheet/u s federal funding for hivaids trends over time/ Accessed April 30, 2017. Currently there are around 18.2 million people on treatment for HIV worldwide 10 million of which through programs supported by T he Global Fund 14 0 In 2015, $33 billion (USD) in cumulative and fully paid contributions from various donors and governments was allocated by The Global Fund to support programs based on national health strategies, and to operate in a balanced manner with in d ifferent regions for HIV, Tuberculosis and Malaria. 14 0 Overall c osts are expected to increase with the 2015 WHO recommendations and policy that delineat es lifelong antiretroviral therapy drugs provided at no cost to HIV positive pregnant women without elig ibility requirements Indicated below, an increase of 6.9 million people are now eligible for antiretroviral therapy drugs, therefore there will be increas ed costs associated.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '$ Source: Doherty M. New directions in the 2015 WHO Consolidated ARV Guidelines. 8 th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), Vancouver, Canada. 2015. National and global organizations need to find sustainable resources in order to implement the new WHO recommendatio ns with future success. Furthermore, HIV positive women may have additional barriers to attaining and complying with antiretroviral therapy drug regimens Although antiretroviral therapy drugs have become available to the at risk population in many develop ing counties, several governments and health clinics still have not adhered to the current WHO recommendations and policy guidelines For many HIV positive women of low socioeconomic stat u s health clinics are far out of reach not only because of transport ation barriers 1 4 1 Owing to the prominent and negative stigmas associated with HIV positive status many women will often travel to different towns altogether in order to receive treatment or pick up appropriate medication for fear of being ostracized from their homes and communities by visiting the nearest health clinic 1 4 2 The perpetual shifts in global health polic y and recommendations, in addition to non adherence pose s difficulties in thwarting mother to child HIV 1 transmission on a global scale

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '% With the WHO's recommendations, and revisions of recommendations, health workers and HIV positive mothers become confused and proper information is not relayed therefore perpe tuating mother to child HIV 1 transmission via breastfeeding Without proper knowledge of current and evidenced based recommendations negative effects can occur Conclusion In the Unites States and other developed count r ies medical advancements have allow ed a less than 2% risk of mother to child HIV 1 transmission 11 Per policy and position statements from the Amer ican Academy of Pediatrics and T he Centers for Disease Control and Prevention, breastfeeding is contraindicated by HIV infectivity. 13 ,120 With maternal and infant antiretroviral medication elective caesarian sections ( C section ), and safe alternative methods to infant feeding, people in developed countries pos e relatively no risk of mother to child HIV 1 transmission. 25 26 However, the complex issues surrounding vertical HIV 1 transmission in developing countries is still prominent today I n 2015, if a person was diagnosed with HIV in one of 13 countries including: Argentina, Australia, Brazil, t he United Kingdom, France, the Maldives, Mexico, t he Nederland's Spain, South Korea, Thailand, Turkey and the United States, policies mandate d that any person with HIV have access to treatment regardless of CD4 count (stage of HIV progression) 14 3 In contrast any other country in the world had policies that prolonged appropriate treatment until eligibility requirements regarding CD4 count were met 14 3 Scientific evidence strongly supports immediate access to HIV treatment as it improves the health of people livin g with HIV, and is one of the most effective tools in decreasing transmission rates 13 6 Up until 2015, most people living with HIV/AIDS in developing countries

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '& had to be sick, or at much greater risk of future illness and premature death, before they could get the treatment that prolongs health while virtually eliminating risk of transmission to others. 14 3 There have been accomplishments and hin drances with various different global health policies and recommendations in the context of mother to child HIV 1 transmission in developing countries. Throughout the years, global health recommendations and policies have shifted with increased research and knowledge surrounding the relatively new disease This shifting has caused significant co nfusion for health workers providing advice to HIV pos itive mothers who have to make the challenging decision of whether or not breastfeeding is best for them and their child A single global health policy and recommendation is warranted to aid in evidence based prevention of mother to child HIV 1 transmission via breastfeeding The current po licy in South Africa eliminates the use of infant formula within low socioeconomic populations which has drastically increased exclusive breastfeeding rates while dec reasing infant morbidity and mortality. Implementing this policy to all endemic HIV/AIDS countr ies will provide the best chance at survival for infant s and mother s alike. South Africa's current policy and recommendations coupled with the WHO's current 2015 policy providing lifelong antiretroviral therapy drugs to all HIV infected mothers will reduce mother to child HIV 1 transmission while prolonging the life of mother and infant. This idea is not perfect. If this policy were implemented globally, many HIV positive mothers would be disadvantaged. Many mothers would have to return to work, or discontinue breastfeeding for other reasons. Some mothers may not seek out antiretroviral therapy drugs attributed to stigma association. Yes, children will become i nfected with HIV, and many will die, but South Africa's current recommendations will be the most effective method to reduce and prevent vertical HIV 1 transmission via breastfeeding in other developing countr ie s. With shifts

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '' in global health policy and rec ommendations causing confusion and doubt, one policy and recommendation needs to hold true in order to enable health workers with the skills to empower HIV positive mothers to seek now available treatment while promoting maternal and infant health above a ll else. In an ideal situation, policy would require places of work to provide safe and appropriate spaces for breastfeeding with adequate stor age, in addition to appropriate time to express. Furthermore health workers would always be up to date on current recommendations and evidenced based care from proper training. There would be no stigma associated to HIV infectivity and a ll HIV positive mothers would effortlessly adhere to antiretroviral therapy drug treatment. This is obviously not realistic, but efforts could be made Through the course of the HIV/AIDS epidemic m any accomplishments have been made with efforts to prevent mother to child HIV 1 transmission most notably, by providing antiretroviral therapy drugs at no cost to HIV positive moth ers T he recent 2015 WHO guideli nes recommend that all pregnant HIV positive women be started on antiretroviral therapy drug treatment regardless of disease stage which enables women to receive the medication they need to reduce t ransmissio n rates, while improving their own health The previous "come back when you're more sick" policies are fortunately changing. The WHO estimates that >95% of pregnant women in South Africa living with HIV (257,456 people) received antiretroviral therapy drugs aimed at pre venting mother to child HIV 1 transmission. 33 In South Africa 53% of HIV positive women are currently on antiretroviral therapy drugs 14 4 However of the 4 million HIV positive women in South Africa aged 15 years and older only 6 .7 % are currently on antiretroviral medication in 2016 32 Assumptions can be made that more than 6 .7 % of the HIV infected population of South Africa is reproducing which

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '( is why many other women are on treatment, although, it is only about half of the female population. The ab ove data is primarily collected f ro m antenatal clinics Therefore, assumptions can be made that a disproportionate number of HIV positive pregnant women are not accessing preventative care. Asking women to seek antiretroviral medication when they bec ome p regnant regardless of clinical stage of HIV is a human rights accomplishment. Although this preventative measure can be improved In order to truly prevent HIV 1 transmission rates not only in the c ontext of mother to child HIV 1 transmission, antiretroviral medications should be provided to all women and truly all HIV infected people As of June 2015 the Joint United Nations Programme on HIV and AIDS estimates that 18. 2 million people globally were acces sing antiretroviral therapy, only 49% of the HIV infected population. 14 5 In contrast to South Africa, only about 77% of all HIV positive women globally had access to antiretroviral therapy treatment aimed at prevent ing HIV 1 transmission from mother to chi ld 14 5 Without access to effective treatment and health services, people are left to illness and death, the rate of new infections will continue to increase With the 2015 WHO recommendations, h ealth workers in developing countries need to be trained t o empower HIV positive soon to be and current mothers to actively seek out antiretroviral therapy drugs to improve their health, while decreasing risk of transmission. In order to truly impact prevention antiretroviral medications should be distributed at no cost to all women who are HIV positive 53 % of the HIV population accessing treatment is not good enough. Additionally, o ne policy in endemic countries should be mandated providing recommendat ions for breastfeeding while HIV positive South Africa alone spent roughly $1.5 billion USD on its HIV/AIDS programs in 2014. 14 6 With South Africa's new commitment to funding lifelong antiretroviral therapy drugs,

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES ') the sustainability of domestic funding will become challenging in the upcoming years. 14 6 W ith hel p from external donors and inter national government financial support, f unds for all countries affected by the HIV/AIDS epidemic could be manageable Financial support would provide the standard of care good enough for HIV infected populations in developed countries, but only recently good enough for HIV infected populations living in developing countries With the current medical knowledge and pharmaceutical drugs, coupled with increased evidenced based knowledge provided to people working on the front lin es, in theory, the HIV /AIDS epidemic could be reduce d to almost nothing in one single generation. At the end of 2015, $19 billion USD was invested in AIDS response programs throughout developing count r ies, with 57% of funding from domestic resources. 14 3 In 2020, estimates indicate $26.2 billion USD will be required for the AIDS response, and $23.9 billion USD in 2030. 14 6 However, t he global economy will pay more for the response to the epidemic in the long run. Paying up and trea ting people now, saves mo ney later. Mother to child HIV 1 transmission and the HIV/AIDS epidemic as a whole is a multifaceted issue there is no single way to fix the problem. The above recommendations regarding increased funding and a ccess to antiretroviral therapy drugs, coupled with implementing a single recommendation and policy in the context of infant feeding and HIV infectivity while empowering HIV positive mothers to access treatment may not be realistic, but why not try.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES '* References 1. The World Health Organization. Global strategy for infant and young child feeding. Geneva, Switzerland. Published 2003. Accessed September, 2016. 2. The Partnership for Maternal, Newborn and Child Health. Newborn death and illness. http://www.who.int/pmnch/media/press_materials/fs/fs_newborndealth_illness/en/ Published 2010. Updated September 2011. Accessed March 2, 2017. 3. Lamberti L, Walker C, Noiman A, Victora C, Black R. Breastfeeding and the risk for diarrhea morbidity and mortality. BMC Public Health 2011;11:S13. 4. Asbjornsdottir K, Slyker J, Weiss N, Mbori Ngacha D, Maleche Obimbo E, Wamalwa D, et al. Breastfeeding is associated with de creased pneumonia incidence among HIV exposed, uninfected Kenyan infants. AIDS 2013;27(17):2809 2815. 5. Tromp I, Kiefte de Jong J, Raat H, Jaddoe V, Franco O, Hofman A, et al. Breastfeeding and the risk of respiratory tract infections after infancy: the ge neration R study. PLos One 2017;12(2):e0172763. 6. The World Health Organization. HIV/AIDS fact sheet. http://www.who.int/mediacentre/factsheets/fs360/en/ Updated November 2016. Accessed J anuary 29, 2017. 7. The Joint United Nations Programme on HIV/AIDS. AIDSinfo: factsheets. http://aidsinfo.unaids.org/ Accessed March 2, 2017. 8. The United Nations Children's Fund. Mother to child transmission of HI V. A UNICEF factsheet. 2002. 9. Cock K, Fowler M, Mercier E, de Vincenze I, Saba J, Hoff E, et. Al. Prevention of mother to child transmission in resource poor countries, translating research into policy and practice. JAMA 2000;283:1175 1182. 10. The World Hea lth Organization. HIV/AIDS Data and Statistics. http://www.who.int/hiv/data/en/ Updated 2016. Accessed January 29, 2017. 11. The World Health Organization. Literature review on HIV and infant feeding. http://www.who.int/nutrition/topics/Paper_5_Infant_Feeding_bangkok.pdf Updated 2007. Access January 30, 2017. 12. The World Health Organization & UNICEF. Guideline: updates on HIV and infant feeding. http://apps.who.int/iris/bitstream/10665/246260/1/9789241549707 eng.pdf?ua=1 Updated 2016. Accessed January 30, 2017. 13. American Academy of Pediatrics. Policy statement: breastfeeding and the use of human milk. Peds 2012;129(3):e827 e841. 14. The World Health Organization. Bulletin of the World Health Organization: breast is best, e ven for HIV positive mothers. 2010;88(1). http://www.who.int/bulletin/volumes/88/1/10 030110/en/ Accessed February 12, 2017.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES (+ 15. The Centers for Disease Control and Prevention. Breastfee ding report card United States 2014. https://www.cdc.gov/breastfeeding/pdf/2014breastfeedingreportcard.pdf Updated July 2014. Accessed February 3, 2017. 16. The United Nati ons Children's Fund. UNICEF Data: monitoring the situation of children and women: adopting optimal feeding practices is fundamental to a child's survival, growth and development, but too few children benefit. https://data.unicef.org/topic/nutrition/infant and young child feeding/# Updated Oct 2016. Accessed February 3, 2017. 17. Brown J. Nutrition through the lifecycle: sixth edition. 2016;6:163 174. 18. Position of the acade my of nutrition and dietetics: promoting and supporting breastfeeding. J Acad Nutr Diet 2015;115:444 449. 19. Ballard O, Morrow A. Human milk consumption: nutrients and bioactive factors. Pediatr Clin North Am 2013;60(1):49 74. 20. The United Nations Children' s Fund. Breastfeeding. https://www.unicef.org/nutrition/index_24824.html Updated July 2015. Accessed February 19, 2017. 21. Phillips R. Uninterrupted skin to skin contact immediately after bir th. NAINR 2013;13(2):67 72. 22. The United Nations Children's Fund. Undernutrition contributes to nearly half of all deaths in children under 5 and is widespread in Asia and Africa. https: //data.unicef.org/topic/nutrition/malnutrition/ Updated February 2017. Accessed March 12, 2017. 23. Vesel L, Bahl R, Martines J, Penny M, Bhandari N, Kirkwood B, et al. Use of new World Health Organization child growth standards to assess how infant malnutrit ion relates to breastfeeding and mortality. WHO 2010;88(1):39 48. 24. The World Health Organization. HIV transmission through breastfeeding: a review of available evidence. 2004:11 15. 25. Lehman D, Farguhar C. Biological mechanisms of vertical human immunodefi ciency virus (HIV 1) transmission. Rev Med Virol 2007;17(6):381 403. 26. Kourtis A, Lee F, Abrams E, Jamieson D, Bulterys M. Mother to child transmission of HIV 1: timing and implications for prevention. Lancet Infect Dis 2006;6(11):726 732. 27. AIDS.gov. What is HIV/AIDS?. https://www.aids.gov/hiv aids basics/hiv aids 101/what is hiv aids/ Updated September 2016. Accessed December 15, 2016. 28. The World Health Organization. HIV/A IDS: Mother to child transmission of HIV. http://www.who.int/hiv/topics/mtct/about/en/ Accessed December 15, 2016. 29. The Joint United Nations Programme on HIV/AIDS. Early diagnosis and treatment saves babies from AIDS related death. http://www.unaids.org/en/resources/presscentre/featurestories/2009/may/20090527unicef Published 2009. Accessed Apri l 20, 2017. 30. The World Health Organization. Fact sheet: countries offering free access to HIV treatment. 2005. http://www.who.int/hiv/countries_freeaccess.pdf Accessed April 20, 2017.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES (" 31. The Jo int United Nations Programme on HIV/AIDS. Press release: HIV treatment now reaching more than 6 million people in sub Saharan Africa. http://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2012/july/2012 0706prafricatreatment Accessed April 20, 2017. 32. The Joint United Nations Programme on HIV/AIDS. AIDSinfo. Data Sheets: Number of people living with HIV. http://aidsinfo.unaids.org/ 2014. Accessed April 1, 2017. 33. The World Health Organization. Global Health Observatory data repository: prevention of mother to child transmission, data by country. http://apps.who.int/gho/data/node.main.627?lang=en Updated April 2016. Accessed April 1, 2017. 34. The Central Intelligence Agency. The world fact book. People and society: South Africa. https://www.cia.gov/library/publications/the world factbook/geos/sf.html Updated January 12, 2017. Accessed March 30, 2017. 35. Wilkinson K. Africa Check: race, poverty and inequality, fact c hecked. https://africacheck.org/reports/race poverty and inequality black first land first claims fact checked/ Published 2015. Accesse d March 30, 2017. 36. Price Check. "baby formula". https://www.pricecheck.co.za/search?search=baby+formula Accessed March 14, 2017. 37. Baby Yum Yum. Formula feeding: what to expect. http://babyyumyum.co.za/formula feeding what to expect/ Updated March 31, 2016. Accessed March 30, 2017. 38. Clicks: Feel Good, Pay Less. Nan Stage 1 Starter Infant Formula 900g. https://clicks.co.za/nestle_nan stage 1 starter infant formula 900g/p/103116 Accessed March 30, 2017. 39. Baby Group. Infant Formula (Stage 1) 900g: Nan 1. https://www.babygroup.co.za/Shop/Feeding/All Feeding/NAN Infant Formula 900g#reviews Accessed March 30, 2017. 40. NUMBEO. Cost of living in South Africa. https://www.numbeo.com/cost of living/country_result.jsp?country=South+Africa Updated April 2017. Accessed April 1, 2017. 41. Skuse D. Non organic failure to thrive: a reapp raisal. Archives of Disease in Childhood 1985;60:173 178. 42. The United Nations. The millennium development goals report. New York, New York. 2014:44 46. 43. United States Agency for International Development. Programming guidance for integrating water, sanita tion, and hygiene improvement into HIV/AIDS programs to reduce diarrhea morbidity. 2008. 44. United Sates Agency for International Development: CDC. Programming Water, Sanitation and Hygiene (WASH) activities in U.S. Government Country Operational Plans (COPs ): A toolkit for FY2009 planning. 2008. 45. WSP. Water, sanitation, and hygiene for people living with HIV and AIDS. Field Note. Water and Sanitation Program 2007.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES (# 46. Water Supply & Sanitation Collaborative Council. HIV/AIDS & WASH. WSSCC Reference Note. 2009. 47. Yates T, Lantagne D, Mintz E, Quick R. The impact of water, sanitation, and hygiene interventions on the health and well being of people living with HIV: a systematic review. J Acquir Immune Defic Syndr 2015;68:S318 S330. 48. Lule J, Mermin J, Ekwaru J, Malamba S, Downing R, Ransom R, et al. Effect of home based water chlorination and safe storage on diarrhea among persons with human immunodeficiency virus in Uganda. Am J Trop Med Hyg 2005;73(5):926 933. 49. Barzilay E, Aghoghovb ia T, Blanton E, Akinpelumi A, Coldiron M, Akinfolayan O, et al. Diarrhea prevention in people living with HIV: an evaluation of a point of use water quality intervention in Lagos, Nigeria. AIDS Care 2011;23(3):330 339. 50. Harris J, Greene S, Thomas T, Ndiv e R, Okanda J, Masaba R, et al. Effect of point of use water treatment and safe water storage intervention on diarrhea in infants of HIV infected mothers. J Infect Dis 2009;200(8):1186 93. 51. Korich D, Mead J, Madore M, Sinclair N, Sterling C. Effects of oz one, chlorine dioxide, chlorine, and monochloramine on Cryptosporidium pavum oocyst viability. Appl Environ Microbiol 1990;56(5):1423 1428. 52. Dunne E, Angoran BŽniŽ H, Kamelan Tano A, Sibailly T, Monga B, Kouadio L, et al. Is drinking water in Abidjan, C™t e d'Ivoire, safe for infant formula? J Acquire Defic Syndr 2001;28(4):393 8. 53. Peletz R, Simuyandi M, Sarenje K, Baisley K, Kelly P, Filteau S, et al. Drinking water quality, feeding practices, and diarrhea among children under 12 years of HIV positive mot hers in peri urban Zambia. Am J Trop Med Hyg 2011;85(2):318 326. 54. Arvelo W, Kim A, Creek T, Legwaila K, Puhr N, Johnston S, et al. Case control study to determine risk factors for diarrhea among children during a large outbreak in country with a high prev alence of HIV infection. IJID 2010;14:e1002 e1007. 55. Oliveria M, Os—rio M. Cow's milk consumption and iron deficiency anemia in children J. Pediatr (Rio J.) 2005;18(5):361 367. 56. Fomon S, Ziegler E. Renal solute load and potential renal solute load in infa ncy. J Pediatr 1999;134(1):11 14. 57. Agostoni C, Turck D. Is cow's milk harmful to a child's health. JPGN 2011;53:594 600. 58. Ziegler E. Consumption of cow's milk as a cause of iron deficiency in infants and toddlers. Nutrition Reviews 2011;69(1):537 542. 59. Guetouache M, Guessas B, Medjekal S. Composition and nutritional value of raw milk. Issues Biol Sci Pharm Res 2014;2(10):115 122. 60. Basnet S, Schneider M, Gazit A, Mander G, Doctor A. Fresh goat's milk for infants: myths and realities a review. Pediatric s 2010;125(4):e973 e977. 61. United States Food and Drug Administration. The dangers of raw milk: unpasteurized milk can pose a serious health risk.

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NUTRITIONAL IMPLICATIONS OF VERTICAL HIV 1 TRANSMISSION VIA BREASTFEEDING IN DEVELOPING COUNTRIES (% 74. Coutsoudis A, Pillay K, Khun L, Spooner E, Tsai W, Coovadia H, et al. Method of feeding and transmission of HIV 1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001;15:379 387. 75. Rol lins N, Filteau S, Coutsoudis A, Tomkins A. Feeding mode, intestinal permeability, and neopterin excretion: a longitudinal study in infants of HIV infected South African women. JAIDS 2001;28:132 139. 76. Visser M, Neufeld S, Villers A, Makin J, Forsyth B. To tell or not to tell: South African women's disclosure of HIV status during pregnancy. AIDS Care 2008;20(9):1138 1145. 77. AVERT. Prevention of mother to child transmission (PMTCT) of HIV. https://www.avert.org/professionals/hiv programming/prevention/prevention mother child Updated 2017.Accessed April 28, 2017. 78. Varga C, Sherman G, Jones S. HIV disclosure in the context of vertical transmission: HIV positiv e mothers in Johannesburg, South Africa. AIDS Care 2005;18(8):952 960. 79. Chisenga M, Siame J, Baisley K, Kasonka L, Filteau S. Determinants of infant feeding choices by Zambian mothers: a mixed quantitative and qualitative study. Ltd Maternal and Child Nutr ition 2011;7:148 159. 80. King C, Ellington S, Kourtis A. The role of co infections in mother to child transmission of HIV. Curr HIV Res 2013;11(1):10 23. 81. Rousseau C, Nduati R, Richardson B, Steele M, John Stewart G, Mbori Ngacha D. Longitudinal analysis o f human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 2003;187(5):741 747. 82. Embree J, Njenga S, Datta P, Nagelkerke N, Ndinya Achola J, Mohanned Z, et al. Risk factors for p ostnatal mother child transmission of HIV 1. AIDS 2000;10(14):2535 2541. 83. Piwoz E, Ross J, Humphrey J. Human immunodeficiency virus transmission during breastfeeding: knowledge, gaps, and challenges for the future. Adv Exp Med Biol 2004;554:195 210. 84. Coutsoudis A. Le Leche League International: current status of HIV and breastfeeding research. http://www.lalecheleague.org/ba/feb05.html Published 2005. Accessed April 22, 2017. 85. Pelto G, Zhang Y Habicht A. Premastication: the second arm of infant and young child feeding for health and survival? Matern Child Nutr 2010;6(1):4018. 86. The World Health Organization. HIV transmission through breastfeeding: a review of available evidence. 2007:11 14. 87. H ummelen R, Hemsworth J, Reid G. Micronutrients, n acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression. Nutrients 2010;2:626 651. 88. Dreyfuss M, Fawzi W. Micronutrients and vertical transmission of HIV 1. Am J Cl in Nutr 2002;75:959 970. 89. Fawzi W, Msamanga G, Spiegelman D, Urassa E, McGrath N, Mwakagile D, et al. Randomized trial of effects of vitamin supplements on pregnancy outcomes and T cell count in HIV 1 infected women in Tanzania. Lancet 1998;351(9114):147 7 82.

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