Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


METHODS
Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points.


METHODS
Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213).


METHODS
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.
Nduati
R
R
Department of Paediatrics, University of Nairobi, Kenya.
John
G
G
Mbori-Ngacha
D
D
Richardson
B
B
Overbaugh
J
J
Mwatha
A
A
Ndinya-Achola
J
J
Bwayo
J
J
Onyango
F E
FE
Hughes
J
J
Kreiss
J
J
D015492:AIDS Serodiagnosis; D000293:Adolescent; D000328:Adult; D001942:Breast Feeding; D003906:Developing Countries; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000503:physiopathology / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007225:Infant Food; D007226:Infant Mortality; D007630:Kenya; D016013:Likelihood Functions; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000503:physiopathology*; D012306:Risk; D016019:Survival Analysis