HIV Prevention Knowledge Base
Biomedical Interventions: Infant Feeding for Mothers Living with HIV
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Breastfeeding in HIV-positive Women: What Can be Recommended?
This comprehensive review article summarizes key studies that examine infant feeding practices and antiretroviral treatment and prophylaxis to reduce mother-to-child transmission of HIV. The studies are grouped by category in three tables: 1) maternal treatment with highly active antiretroviral therapy (HAART) [Note: although the authors refer to HAART, the table includes women given highly active antiretroviral drugs solely as prophylaxis to prevent mother-to-child transmission]; 2) infant HIV prophylaxis; and 3) upcoming trials of maternal antiretroviral therapy or infant HIV prophylaxis. The authors conclude that well-designed studies show that infant prophylaxis with antiretroviral drugs during breastfeeding can reduce HIV transmission to as low as 1.2 percent at 6 weeks to 6 months. A combination of maternal HAART (or antiretroviral drugs for prophylaxis) and infant prophylaxis for the duration of breastfeeding, say the authors, could “effectively eliminate” mother-to-child transmission of HIV where formula is not acceptable.
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HIV Prevention is Not Enough: Child Survival in the Context of Prevention of Mother to Child HIV Transmission
Prevention of HIV transmission is not enough, according to the authors of this commentary, who say that measures to improve maternal health and child survival must also be addressed. The authors review key pitfalls of some prevention programs, from earlier attempts to encourage all women living with HIV to abstain from breastfeeding (which led to a sixfold increase in child mortality in Uganda), to the tendency to conduct prevention activities such as voluntary testing and counseling in urban areas. Because some prophylactic antiretroviral regimens are administered during, prior to, or just after a child’s birth, many children of mothers with HIV are left unprotected during breastfeeding—a period when 40 percent of children with HIV will acquire the virus.
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Maternal Highly Active Antiretroviral Treatment (HAART): Does it Improve Child Survival?
This clinical trial conducted in Malawi evaluated HIV-free survival rates of children whose mothers were categorized into one of three groups: group A, highly active antiretroviral therapy (HAART)-ineligible (defined as a CD4 count of 250 or greater); group B, HAART-eligible but untreated women; and group C, HAART-eligible and treated women. At 24 months, HIV-free survival of infants was 82 percent in group A; 68 percent in group B; and 81 percent in group C. When survival rates were adjusted for various infant prophylaxis regimens, the risk of death among the children of treated mothers and treatment-ineligible mothers were each approximately half that of the children of treatment-eligible but untreated women.
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Triple-antiretroviral (ARV) Prophylaxis During Pregnancy and Breastfeeding Compared to Short-ARV Prophylaxis to Prevent Mother-to-child Transmission of HIV-1 (MTCT): the Kesho Bora Randomized Controlled Clinical Trial in Five Sites in Burkina Faso, Kenya
This study, conducted in Burkina Faso and Kenya, randomized 824 pregnant women living with HIV and with CD4 counts of 200 to 500 to receive either triple antiretroviral (ARV) prophylaxis or short-ARV prophylaxis. Over three-quarters of infants in both groups were breastfed. Infants in both groups were treated with single-dose nevirapine. At 12 months, the cumulative HIV infection rates among infants born to women receiving triple-ARV and short-ARV were 5.6 percent and 9.3 percent, respectively; however, there was no statistically significant difference in overall mortality.
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Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission
This study randomized 2,637 mother-infant pairs, in which the mothers had CD4 counts higher than 250, to receive either maternal triple drug prophylaxis (referred to by the authors as highly active antiretroviral therapy), infant nevirapine, or no additional prophylaxis (all pairs were treated with single-dose nevirapine and one week of two-drug prophylaxis immediately after birth). Treatment extended up to 28 weeks of breastfeeding, and mothers breastfed exclusively for 24 weeks, followed by rapid weaning. Preliminary data show that at one week, 4.9 percent of infants in the two treatment groups were infected, reflecting transmission during pregnancy. At 28 weeks, 6.4 percent of infants in the control arm (those with no additional treatment) developed HIV; 3.0 percent of infants born to mothers treated with triple drug prophylaxis became HIV-positive; and 1.8 percent of infants treated with nevirapine became infected. Revised results will be published in an upcoming issue of the New England Journal of Medicine.
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Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana
Five hundred and sixty women living with HIV with CD4 counts of 200 or higher were randomized to receive one of two triple drug regimens (referred to by the authors as highly active antiretroviral therapy): Arm A received abacavir/zidovudine/lamivudine and Arm B received lopinavir/ritonavir/Combivir, which were prescribed at 26 to 34 weeks of pregnancy through 6 months following birth. A control group of 170 women with CD4 counts less than 200 were treated with nevirapine/Combivir. Seven of 10 mothers breastfed for five months or longer. Neither infant mortality nor HIV transmission differed significantly among the groups. Infant mortality at six months did not differ by groups and was very low in all arms.
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Interventions for Preventing Late Postnatal Mother-to-Child Transmission of HIV
This systematic review of clinical trials of prevention of mother-to-child transmission of HIV during breastfeeding found that up to 42 percent of transmission occurs during breastfeeding. Mothers who had a high viral load; were young; did not breastfeed exclusively; or who had breast lesions were more likely to transmit HIV to their infants. In low-resource areas with poor sanitation, infants were more likely to die of diarrheal diseases and pneumonia when not exclusively breastfed—completely offsetting deaths from HIV at 2 years. The authors suggest that for mothers who initiate breastfeeding, a) breastfeeding should be exclusive, and b) extended prophylaxis should be given to the infant (nevirapine alone or nevirapine with zidovudine).
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Population-based Study of a Widespread Outbreak of Diarrhea Associated with Increased Mortality and Malnutrition in Botswana, January-March, 2006
An outbreak of diarrhea led to an abrupt increase in acute malnutrition and deaths among children younger than 5 years old in Botswana. The outbreak occurred during a period of heavy rains when sewage may have flooded the water supply. The study authors examined risk factors for diarrhea, including the HIV status of mother and child; contamination of the water supply; presence of flush toilets; and breastfeeding. Approximately one-third of mothers were living with HIV and, as a result of local prevention counseling against breastfeeding, almost none of these mothers breastfed, whereas almost half of uninfected mothers did breastfeed. HIV status of the infant and failure to breastfeed were correlated with the risk of diarrhea.
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Effects of Early, Abrupt Weaning on HIV-free Survival of Children in Zambia
In an attempt to balance the benefits of breastfeeding with reduced risk of HIV transmission by reducing exposure time, researchers randomized mother-infant pairs to early, abrupt cessation of breastfeeding at four months or to a control group that breastfed as long as desired. Children who were infected with HIV at four months were somewhat less likely to survive to 24 months if breastfeeding was stopped early. However, there was no statistically significant difference in overall child survival at 24 months in the two groups: approximately one-quarter of the children in the intervention arm and the control arm had died by 24 months. The authors conclude that the failure of early breastfeeding cessation and its associated costs did not justify such an approach.
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Survival of Infants Born to HIV-positive Mothers, by Feeding Modality, in Rakai, Uganda
Mothers living with HIV who chose to breastfeed were compared to those who chose to formula feed their infants. Eligible mothers received antiretroviral treatment and those who were not eligible received antiretroviral drugs to prevent mother-to-child transmission of HIV. Only one-quarter of mothers practiced exclusive breastfeeding at one month. Although formula-fed infants were less likely to become HIV-infected at one month, they were six times as likely to die by 12 months compared to breast-fed infants. Formula feeding was particularly risky for HIV-positive infants; all 3 formula-fed HIV-positive infants died by 12 months, compared to none of the 12 breast-fed HIV-positive infants.
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Bacterial Contamination and Over-Dilution of Commercial Infant Formula Prepared by HIV-Infected Mothers in a Prevention of Mother-to-Child Transmission (PMTCT) Programme
Formula prepared by mothers in Durban, South Africa, had high levels of fecal contamination. The mothers, who participated in a program to prevent mother-to-child transmission of HIV, all said that they boiled the water before preparing formula. Some of the mothers stored the boiled water for later use, however, which significantly increased the risk of contamination. Other factors associated with contamination included storing leftover formula for later feeds and the use of unboiled water to rinse previously sterilized bottles. Although mothers correctly diluted powdered formula for younger infants, they tended to overdilute formula for older children. Some mothers put extra scoops of powder in the feed, mistakenly thinking the baby “needs it,” a practice that puts the child at risk of potentially fatal problems from too much salt and sugar in the bloodstream.
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High Uptake of Exclusive Breastfeeding and Reduced Early Post-natal HIV Transmission
This prospective, observational study examined the hypothesis that exclusive breastfeeding would reduce mother-to-child HIV transmission. Some study mothers received either single-dose nevirapine for prophylaxis or antiretroviral treatment. Infants who were exclusively breastfed were at least half as likely to acquire HIV at four months of age as infants of mothers who practiced non-exclusive breastfeeding. Eighty-four percent of the 958 mothers in the study practiced exclusive breastfeeding at four months. The researchers review factors hypothesized to increase HIV transmission during mixed feeding, and add a new hypothesis of their own.
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Mother-to-Child Transmission of HIV Infection During Exclusive Breastfeeding in the First 6 Months of Life: An Intervention Cohort Study
Mothers in this study were encouraged to either exclusively breastfeed or to exclusively use replacement feeds if they chose not to breastfeed. Infants who received mixed feedings were, by three months, nearly 11 times as likely to become HIV infected as infants receiving exclusive breastfeeding. Infants who received replacement feeds for three months were more than twice as likely to die as infants who were exclusively breastfed. The authors state that 210,000 to 270,000 new HIV infections acquired by breastfeeding annually could be averted if mothers are encouraged to stop exclusive breastfeeding at six months (around 4 percent transmission) rather than the “more usual 18–24 months of mixed feeding” (16 percent transmission).
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Effect of the HIV Epidemic on Infant Feeding in South Africa: “When They See Me Coming with the Tins they Laugh at Me”
Mothers interviewed about their infant-feeding practices were selected from a cohort that had achieved some success in either exclusive breastfeeding or exclusive formula feeding. Despite the relative success of this cohort, 80 percent of breastfeeding mothers introduced other liquids to the infant’s feeds within the first month. Factors that led to mixed feedings included conflicting health care messages (posters promoting breastfeeding and formula feeding were found in the same clinic); pressure from mothers, mothers-in-law, and grandmothers to add other liquids; and secrecy regarding the diagnosis of HIV, which led many women to reject recommended feeding practices out of fear that it would make their diagnosis obvious if they chose to exclusively formula feed or to stop breastfeeding early.
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Breastfeeding Plus Infant Zidovudine Prophylaxis for 6 Months vs Formula Feeding Plus Infant Zidovudine for 1 Month to Reduce Mother-to-Child HIV Transmission in Botswana: A Randomized Trial: The Mashi Study
This small study examines transmission of HIV from mother to child during the postnatal (after birth and during breastfeeding) period. Breastfed infants who received zidovudine prophylaxis for six months were compared to formula-fed infants given one month of infant zidovudine. Three-quarters of mothers practiced mixed feeding. HIV infection at seven months was somewhat higher (9 percent) in the breastfed group than in the formula-fed group (5.6 percent); however, mortality at the same time was higher in the formula-fed group (9.3 percent) compared to the breastfed group (4.9 percent). HIV-free survival was similar between the two groups by 18 months.
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Early Exclusive Breastfeeding Reduces the Risk of Postnatal HIV-1 Transmission and Increases HIV-free Survival
This large study assessed the risk of mother-to-child transmission (MTCT) of HIV among mothers who practiced exclusive breastfeeding, predominant breastfeeding, or mixed feeding. Mixed breastfeeding was associated with the highest risk and exclusive breastfeeding with the lowest risk of MTCT. Mixed breastfeeding infants were 2.6 times as likely to become HIV positive at 18 months, and predominantly breastfed infants were 1.6 times as likely as exclusively breastfed infants to become HIV positive. Only 7.6 percent of infants were exclusively breastfed for at least three months. By six months, 93 percent of infants received early mixed feedings. More than two-thirds of the breastfeeding transmission occurred after six months. Maternal CD4 <200 was significantly associated with postnatal transmission.
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Morbidity and Mortality in Breastfed and Formula-Fed Infants of HIV-1-infected Women: A Randomized Clinical Trial
The authors previously reported that the risk of mother-to-child transmission of HIV from breastfeeding is 16 percent. Among infants with HIV, up to 44 percent acquired the infection from breastfeeding. In this study, mothers living with HIV were randomized to either breastfeed or formula-feed their infants. Infant mortality at two years was similar in the two groups (approximately 1 of every 4 or 5 infants died by their second birthday). However, as HIV-free survival was higher in the formula-fed group, the authors concluded that “formula feeding can be a safe alternative to breastfeeding.” The authors acknowledge that their study represents a “best-case scenario” as the mothers all had access to potable water, a reliable source of formula, and ready access to medical care.
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Non-Antiretroviral Approaches to Prevention of Breast Milk Transmission of HIV-1: Exclusive Breastfeeding, Early Weaning, Treatment of Expressed Breast Milk
This chapter describes the evidence on three strategies of infant feeding (exclusive breastfeeding, early weaning, and treatment of expressed breast milk) to reduce the likelihood of HIV transmission from an HIV-positive mother to her infant. The evidence for the reduced transmission of HIV to infants when mothers exclusively breastfeed is strong. The theories given on why mixed feeding may increase HIV transmission include: 1) mixed feeding damages an infant’s intestinal mucosa which then facilitates HIV infection, and 2) mixed feeding may cause the mother’s breasts to have subclinical mastitis that increase the breast milk’s viral loads. However, further studies on these two theories have disproven them, and research is still necessary to further investigate them. Early weaning was thought to be a strategy in reducing HIV transmission to infants since it reduced their exposure to the virus; however, it was found that early weaning could cause increased morbidity and mortality to HIV-positive infants and had no effect among HIV-negative infants. The World Health Organization (WHO) no longer recommends this strategy. Treating breast milk with microbicides to inactivate HIV-1 was successfully reported in one study but subsequent research could not replicate the findings. Another study attempted to inactivate HIV by leaving breast milk at room temperature for six hours, but this was found to be ineffective as well. Direct and indirect heat treatment of breast milk are two prevention of mother-to-child transmission strategies. However, direct heat treatment often leads to loss of important nutrients in the milk. There are two types of indirect heat treatments—“Pretoria pasteurization” and “flash heat”—and both had positive results, but more research is needed to conclusively recommend these methods. WHO updated its guidelines on HIV-1 and infant feeding in 2010 based on the current evidence.
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Maternal and Infant Antiretroviral Regimens to Prevent Postnatal HIV-1 Transmission: 48-week Follow-up of the BAN Randomised Controlled Trial
This article describes a follow-up study of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial, which assessed the effectiveness of 28 weeks of use of maternal or infant antiretroviral (ARV) prophylaxis on postnatal HIV infection at 48 weeks. The study also examined the effects on breastfeeding cessation and on maternal and infant deaths, as well as serious adverse events. The original BAN randomized clinical trial provided mothers and infants with antiretroviral therapy (maternal triple ARVs, infant nevirapine, or ARVs for both before and during labor but not after the birth) to prevent postnatal HIV-1 transmission. According to the authors, the 48-week follow-up study has demonstrated that both infant and maternal prophylaxis effectively reduces postnatal HIV-1 transmission, and that the protective benefits continue after breastfeeding ends. They report that once mothers wean their infants from breastfeeding, there is an increase in HIV transmission, infant morbidity, and mortality. They particularly point out that weaning at six months or less may increase infant morbidity. Due to these results, the authors recommend breastfeeding with prophylaxis for more than 28 weeks. They also remind readers that the World Health Organization now recommends that HIV-positive mothers or uninfected infants receive antiretroviral prophylaxis for 12 months of breastfeeding.
