Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

Abstract

Peripartum administration of single-dose nevirapine reduces mother-to-child trans- mission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine- resistant virus. Methods In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single- dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or te- nofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The pri- mary end point was the time to confirmed virologic failure or death. Results A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopin­avir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single- dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. Conclusions In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtri­ citabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretro- viral therapy. (Funded by the National Institute of Allergy and Infectious Disease