Baseline characteristics were well-matched between feeding arms (data not shown). Infant PCR testing occurred within 4 days of birth for 96% of infants, and later PCR testing occurred within 4 days of the scheduled 1-, 4-, and 7-month visits for 92% of infants. Of 1116 infants alive and HIV-free at birth, 6 (1.1%) in the FF arm and 7 (1.3%) in the BF arm were identified as infected between birth and 1 month (P = .99), representing transmission either intrapartum or during early breast-feeding. In the FF arm, no breast-feeding was reported to have occurred among the 6 infants who were infected during the first month.
Maternal receipt of single-dose NVP was not a significant predictor for MTCT between birth and 1 month in the BF arm (P
= .45). There was a nonsignificant trend for early protection from maternal receipt of NVP in the FF arm (P
= .12); this trend was only apparent during the first study era, before all infants received prophylactic NVP and before HAART became available for women with advanced disease. displays the breakdown of transmission between birth and 1 month by maternal and infant receipt of NVP or placebo in each feeding arm. Pharmacologic testing supported maternal self-report of NVP receipt for 95 of 96 randomly selected women [6
]. Because 937 (80%) of 1179 live-born infants in the study were randomized to receive single-dose NVP, our ability to assess the importance of the infant dose for preventing transmission of HIV during early breast-feeding was diminished. In the latter half of the study, 71 women who were receiving HAART at the time of delivery (i.e., women with a CD4 cell count <200 cells/mm3
or AIDS) did not receive single-dose NVP or placebo, which limited our ability to evaluate its effect at lower CD4 cell counts.
Timing of mother-to-child transmission of HIV (MTCT) in the Mashi Study, by randomized feeding strategy.
Of 547 infants in the BF arm who were alive and HIV-uninfected at 1 month of age, late MTCT occurred in 24 (4.4%); it occurred in 15 infants before 4 months of age, in 6 during the period from month 4 to 6, and in 3 during the period from month 7 to 24 (). An additional 4 transmissions occurred during the first 2 months of life, but the timing could not be determined to be either early or late because of missing PCR results at birth (for 1 infant) or at 1 month (for 3 infants). In the FF arm, 2 infants became infected after the 1 month visit, and 2 became infected at an undetermined time point.
Among the at-risk infants in the BF arm, univariable associations with late MTCT included higher baseline maternal plasma HIV-1 RNA level (P < .001), higher breast milk HIV-1 RNA level (P < .001), lower baseline maternal CD4 cell count (P = .004), and maternal death (P = .006). In multivariable analysis (which excluded breast milk HIV-1 RNA level, because it was colinear with plasma HIV-1 RNA level), maternal HIV-1 RNA level (P = .005), maternal CD4 cell count (P = .06), and lack of electricity in the home (P = .05) predicted late MTCT (). The duration of infant ZDV prophylaxis did not predict late MTCT (P = .98). Four (16.7%) of the 24 late transmissions occurred among infants whose prophylactic ZDV had been stopped prior to their first positive HIV test result. Maternal receipt of single-dose NVP did not predict late MTCT. Although not significant, no MTCT occurred among 34 breast-fed infants whose mothers started HAART before delivery.
Selected risk factors for mother-to-child transmission of HIV via breast-feeding after >1 month of breast-feeding.
Among infants with complete feeding information at each time point, 420 (77%) of 546 were exclusively breast-feeding at 1 month, but only 109 (21%) of 526 were exclusively breast-feeding by 5 months. Feeding method was not a significant predictor of late MTCT (P = .55, by Cox proportional hazards modeling). The progression to mixed feeding over time did not differ when late-infected and uninfected infants were compared.
The median baseline maternal CD4 cell count among women who transmitted HIV during late breast-feeding was 225 cells/ mm3 (interquartile range [IQR], 122-399 cells/mm3). The median baseline maternal HIV-1 RNA level among women who transmitted HIV during late breast-feeding was 4.9 log10 copies/mL (IQR, 4.5-5.5 log10 copies/mL). No late MTCT occurred when the HIV-1 RNA level was <3500 copies/mL.