Mother-to-child transmission (MTCT) of HIV is the primary way that children become infected with HIV. Such transmission can take place when the child is still in the mother’s womb, around the time of birth, or through breastfeeding after birth. Hundreds of thousands of children are infected this way every year, with most of them in developing countries. Major progress has been made in preventing MTCT when the baby is still in the mother’s womb, or around the time the baby is born. In many resource-rich settings, mothers with HIV infection are counseled not to breastfeed their children, and there are feasible and affordable alternatives to breastfeeding. However, in parts of the world where the vast majority of mothers with HIV infection live, complete avoidance of breastfeeding is often not feasible (for example, because of the lack of availability of clean water and of affordable replacement feeding). Therefore, interventions to prevent transmission of HIV infection through breast milk are urgently needed. The authors found that, in addition to complete avoidance of breastfeeding if safe and affordable, exclusive breastfeeding (where the baby receives only breast milk) for the first few months of life helps prevent transmission (as compared to breastfeeding supplemented by feeding the baby other liquids or solids). Another intervention, giving the baby an anti-HIV medicine (antiretroviral) while breastfeeding, decreases the risk of transmission of HIV from mother to child. Implementation of such interventions, as well as developing more and better interventions, is essential.
Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2) extended antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission.
Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection. Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented. However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission.
The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival.
Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative.
Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis. Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality).
Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies.
Six randomized clinical trials and one intervention cohort study were included in this review. Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding abruptly around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT by six months of age according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids any time after birth (hazard ratio = 10.87, 1.51-78.00, p = 0.018). Cumulative 3-month mortality among formula fed infants was higher than among exclusively breastfed infants (hazard ratio = 2.06, 1.00-4.27, p = 0.051). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. In one trial conducted in Botswana, mothers received zidovudine prophylaxis beginning at 34 weeks gestation and during labor, and mother and infants were randomized to receive a two-dose nevirapine regimen or placebo. Infants were randomized to six months of breastfeeding with zidovudine prophylaxis (breastfeeding+zidovudine) or formula feeding with one month of infant zidovudine (formula+zidovudine). Mothers were instructed to initiate and complete weaning between five and six months of age. Breastfeeding+zidovudine (transmission rate = 9.0%) was not as effective as formula+zidovudine (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding+zidovudine and formula+zidovudine had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended infant nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, mothers were counseled to breastfeed exclusively for six months and to consider weaning thereafter. Nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of two-dose nevirapine prophylaxis (10.6%) (p < 0.001). HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group.