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%; P=.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.
Coutsoudis
Anna
A
Dabis
Francois
F
Fawzi
Wafaie
W
Gaillard
Philippe
P
Haverkamp
Geert
G
Harris
D Robert
DR
Jackson
J Brooks
JB
Leroy
Valerie
V
Meda
Nicolas
N
Msellati
Philippe
P
Newell
Marie-Louise
ML
Nsuati
Ruth
R
Read
Jennifer S
JS
Wiktor
Stefan
S
D001942:Breast Feeding / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008895:Milk, Human / Q000821:virology*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors