Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

The findings of a number of observational or uncontrolled studies suggested that initiation of an antiretroviral regimen during the antenatal period and continuation postpartum markedly reduced rates of postnatal human immunodeficiency virus type 1 (HIV-1) transmission during breast-feeding by 6 months after birth. Two randomized controlled trials reported that nevirapine administration to infants prevented HIV-1 transmission during breast-feeding. There are no published studies comparing infant and maternal interventions. This randomized controlled trial evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine administration in reducing postpartum HIV transmission during 28 weeks of breast-feeding. A total of 2369 HIV-1–positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants were randomly assigned to receive a maternal antiretroviral regimen (n = 849), infant nevirapine (n = 852), or to a control group (n = 668). The study was conducted at antenatal clinics in Malawi. Perinatal prophylaxis in all mothers in labor and their newborn infants was a single oral dose of nevirapine and zidovudine plus lamivudine for 1 week. The primary efficacy end points were the rate of infant HIV-1 infection or the composite outcome of HIV-1 infection or death. The Kaplan–Meier method was used to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were uninfected (HIV-1–negative) at 2 weeks after birth. Two-sided log-rank tests were used to estimate differences between the intervention groups and the control group. At 2 weeks, the estimated risks of infection were similar in the 3 study groups (control group, 5.4%; maternal-regimen group, 5.5%; P = 0.97; and infant-regimen group, 4.4%; P = 0.35). Among infants (HIV-1–negative) at 2 weeks, the estimated risk of HIV-1 infection between 2 and 28 weeks was 5.7% in the control group, 2.9% in the maternal-regimen group (P = 0.009), and 1.7% in the infant-regimen group (1.7%, P < 0.001). Similarly, the estimated risk of infection or death by 28 weeks among infants HIV-1–negative at 2 weeks was significantly lower in the intervention groups (7.0% in the control group, 4.1% in the maternal-regimen group; P = 0.02, and 2.6% in the infant-regimen group; P < 0.001). The incidence of grade 3 or 4 neutropenia among mothers who received the antiretroviral regimen was higher (6.2%) compared with the infant-regimen group (2.6%) or the control group (2.3%). A hypersensitivity reaction developed in 1.9% of the infants receiving nevirapine. These findings indicate that both a maternal antiretroviral regimen and an infant nevirapine regimen during 28 weeks of breast-feeding were effective in reducing postnatal HIV-1 transmission compared with a control regimen. Accordingly, these data provide evidence for 2 effective options to prevent maternal-to-infant transmission of HIV-1 during breast-feeding in resource-limited countries.