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A Randomized Clinical Trial

Ruth Nduati, MBChB, MPH; Grace John, MD, MPH; Dorothy Mbori-Ngacha, MBChB, MPH; Barbra Richardson, PhD; Julie Overbaugh, PhD; Anthony Mwatha, MS; Jeckoniah Ndinya-Achola, MBChB; Job Bwayo, MBChB, PhD; Francis E. Onyango, MBChB, MPH; James Hughes, PhD; Joan Kreiss, MD, MSPH

JAMA. 2000;283:1167-1174.

Context  Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries 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 formula-fed infants.

Design and Setting  Randomized clinical trial conducted from November 1992 to 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 end 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 years of life, compared between the 2 intervention groups.

Results  Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding 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 probability 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 transmission 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 transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding 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 was 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 early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1–free survival.

Author Affiliations: Departments of Paediatrics (Drs Nduati, Mbori-Ngacha, and Onyango) and Medical Microbiology (Drs Ndinya-Achola and Bwayo and Mr Mwatha), University of Nairobi, Nairobi, Kenya; Departments of Epidemiology (Dr Kreiss), Medicine (Drs John and Kreiss), Biostatistics (Drs Richardson and Hughes), and Microbiology (Dr Overbaugh), University of Washington, Seattle.

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