BACKGROUND: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants. METHODS: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method. RESULTS: Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. CONCLUSIONS: Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).