Late Postnatal Transmission of HIV-1 in Breast-Fed Children: An Individual Patient Data Meta-Analysis

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Abstract

Background.

We analyzed individual patient data to determine the contribution of late postnatal transmission to the overall risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) and the timing and determinants of late postnatal transmission.

Methods.

Eligible trials were conducted where breast-feeding was common; included ≥2 HIV-1 tests by 3 months, and, if follow-up continued, ≥2 tests at 3-12 months; and regularly assessed infant-feeding modality Data on children born before January 2000 were analyzed.

Results.

Of 4085 children from 9 trials (breast-fed singletons for whom HIV-1 testing was performed), 993 (24%) were definitively infected (placebo arms, 25.9%; treatment arms, 23.4%; =.08). Of 539 children with known timing of infection, 225 (42%) had late postnatal transmission. Late postnatal transmission occurred throughout breast-feeding. The estimated hazard function for time to late postnatal transmission was roughly constant. The cumulative probability of late postnatal transmission at 18 months was 9.3%. The overall risk of late postnatal transmission was 8.9 transmissions/100 child-years of breast-feeding and was significantly higher with lower maternal CD4+ cell counts and male sex.

Conclusions.

Late postnatal transmission contributes substantially to overall mother-to-child transmission of HIV-1. The risk of late postnatal transmission is generally constant throughout breast-feeding, and late postnatal transmission is associated with a lower maternal CD4+ cell count and male sex. Biological and cultural mechanisms underlying the association between sex and late postnatal transmission should be further investigated. Interventions to decrease transmission of HIV-1 through breast-feeding are urgently needed.

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