Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial

Context  A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal humanimmunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatalantiretroviral therapy (ART). However, it is unknown whether the additionof the 2-dose nevirapine regimen to standard ART would further reduce perinatalHIV transmission. Objective  To determine whether a 2-dose nevirapine regimen can decrease perinataltransmission of HIV in nonbreastfeeding women receiving standard ART. Design and Setting  International, blinded, placebo-controlled, phase 3 trial enrollingwomen between May 1997 and June 2000 at clinical sites providing care forHIV infection throughout the United States, Europe, Brazil, and the Bahamas. Participants  A total of 1270 women received nevirapine (n = 642) or placebo (n =628). Infants were followed up for 6 months to determine HIV-infection status,which was available for 1248 deliveries. Intervention  A 200-mg dose of oral nevirapine to women after onset of labor and a2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours afterbirth. Main Outcome Measures  Detection of HIV infection in infants and grade 3 and 4 toxic effectsin women and newborns. Results  After review by the data and safety monitoring board, the trial wasstopped early because the overall transmission rates were significantly lowerthan assumed for the study design. Antenatal ART included zidovudine alonein 23%; combinations without protease inhibitors in 36%; and combinationswith protease inhibitors in 41%. Thirty-four percent of women had electivecesarean delivery. No significant safety concerns were identified for womenor infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidenceinterval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%;95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the differencein transmission rate (-0.2) between the 2 study arms ranged from -1.5%in favor of nevirapine to 1.2% in favor of placebo (P= .82, Fisher exact test). The transmission rate was higher in women withlower baseline CD4 cell counts and higher delivery HIV RNA levels, but therewas no significant difference between treatment arms in any subgroup. Conclusion  Risk of perinatal HIV transmission was low and no benefit from additionalintrapartum/newborn nevirapine was demonstrated when women received prenatalcare and antenatal ART, and elective cesarean section was made available.