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

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.

Mother-to-child transmission of HIV-1 can occur in utero, during delivery, and postnatally through breastfeeding [1]. In settings where breast-feeding is the norm, a significant proportion of mother-to-child transmission of HIV-1 occurs through breast-feeding [2]. However, more information is needed with regard to the risk and timing of transmission through breast-feeding and potential risk factors for such transmission.

To inform the development of appropriate interventions to prevent transmission through breast-feeding in areas of the world where complete avoidance of breastfeeding is not, generally, feasible, we conducted an individual patient data meta-analysis of transmission of HIV-1 through breast-feeding. The objectives were the following: to estimate the contribution of late postnatal transmission of HIV-1 to the overall risk of mother-to-child transmission of HIV-1 and to characterize the timing and determinants of late postnatal transmission.