ContextDespite the success of highly active antiretroviral therapy, the optimal approach for preventing perinatal HIV-1 transmission is not known.ObjectiveA retrospective survey was conducted at six centers in the United States and Puerto Rico from January 1997 to October 1998 to evaluate the effects of protease inhibitor use during pregnancy on maternal and infant safety, prematurity rate, and frequency of perinatal HIV-1 transmission.ResultsIn the study, 91 live infants, including 3 sets of twins, and 1 neonate who died shortly after birth were born to 89 women. HIV perinatal transmission rate in this series was 0 (95% confidence interval [CI], 0%–3%). Prematurity rate was 19.1%, comparable to rates in earlier reports of HIV-1–infected women. In multiple regression analysis, only cocaine use and premature rupture of membranes were associated with prematurity (p= .03 and .008, respectively). The gestational week during which the protease inhibitors were initiated was not found to be significantly associated with prematurity. Adverse maternal, obstetric, and infant events possibly related to protease inhibitors were uncommon.ConclusionsProtease inhibitors appeared generally safe in mothers and infants in this series. No perinatal HIV-1 transmission occurred. Further prospective, controlled studies are needed to define the optimal management of HIV-1 in pregnancy.