Effect of breastfeeding and formula feeding on transmission of HIV-1 - A randomized clinical trial

Context Transmission of human immunodeficiency virus type 1 (HIV-1) is know n to occur through breastfeeding, but the magnitude of risk has not been pr ecisely defined. Whether breast milk HIV-1 transmission risk exceeds the po tential risk of formula-associated diarrheal mortality in developing countr ies is unknown. Objectives To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and for mula-fed infants. Design and Setting Randomized clinical trial conducted from November 1992 t o July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. Participants Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial e nd points. Interventions Mother-infant pairs were randomized to breastfeeding (n = 212 ) vs formula feeding arms (n = 213). Main Outcome Measures Infant HIV-1 infection and death during the first 2 y ears of life, compared between the 2 intervention groups. Results Compliance with the assigned feeding modality was 96% in the breast feeding arm and 70% in the formula arm (P<.001). Median duration of breastf eeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative prob ability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P=.001). The estimated rate of breast milk transmissio n was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk tra nsmission occurred early, with 75% of the risk difference between the 2 arm s occurring by 6 months, although transmission continued throughout the dur ation of exposure. The 2-year mortality rates in both arms were similar (br eastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P=.30). The rate of HIV-1-free survival at 2 years w as significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P=.02). Conclusions The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred ea rly during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-f ree survival.