Independent effects of nevirapine prophylaxis and HIV-1 RNA suppression in breast milk on early perinatal HIV-1 transmission

Abstract

Background: The mechanism of action of single-dose nevirapine on reducing mother-to-child transmission of HIV-1 may involve reduction of maternal HIV-1 or prophylaxis of infants.

Methods: In a study that randomized pregnant mothers to HIVNET 012 nevirapine versus short-course antenatal zidovudine, we compared breast milk HIV-1 RNA viral shedding and administration of single-dose nevirapine between mothers who transmitted HIV-1 to their infants at 6 weeks postpartum and those who did not.

Results: In multivariate analyses, maximum breast milk HIV-1 RNA levels (hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.25 to 4.99; P = 0.01) and nevirapine use (HR = 0.12, 95% CI: 0.02 to 0.97; P = 0.05) were each independently associated with perinatal transmission at 6 weeks postpartum. Mothers who transmitted HIV-1 to their infants had significantly higher HIV-1 RNA levels in their breast milk between the second day and sixth week postpartum. Among mothers with maximum breast milk virus levels less than a median of 3.5 log(10) copies/mL, the administration of nevirapine further decreased HIV-1 transmission risk from 22.2% to 0.0% (P = 0.04).

Conclusions: Peripartum administration of single-dose nevirapine to mother and infant decreases early perinatal HIV-1 transmission by means of breast milk HIV-1 RNA suppression and, independently, by providing the infant with exposure prophylaxis.

Conflict of interest statement

The authors do not have a commercial or other association that might pose a conflict of interest.

Figures

FIGURE 1

Mean log10 HIV-1 RNA in breast milk over days postpartum of HIV-1 mother-to-child transmitters (T) versus nontransmitters (NT) at 6 weeks postpartum (lines are Loess curves).

FIGURE 2

Kaplan-Meier curves of maximum breast milk log10 HIV-1 RNA viral level (BMVL) greater than and at or less than the median (3.5 log10 copies/mL) and nevirapine (NVP) administration on cumulative HIV-1 perinatal infection. The P value for a difference in the 4 groups (log-rank test) is 0.04.