Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

Abstract

BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission 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 tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary 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–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.)

Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine

“…Of the 241 women enrolled in trial 1, 42 women reached a primary endpoint (death or virological failure); about three-quarters of these were in the NVP arm. The distribution of deaths and failures was similar in the two arms: four deaths of 32 endpoints in the NVP arm compared with one death of 9 endpoints in the LPV/r arm (12). Of the 239 women for whom population genotypes were obtained at baseline, 33 had NVP resistance mutations: 15 (13%) of 120 women in the NVP arm and 18 (15%) of 119 women in the LPV/r arm.…”

“…The results of the primary analysis of trial 1 (12), stratified by standard population genotype result at study entry for NVP resistance, are summarized in Fig. 1A.…”

“…The study population was described in detail by Lockman et al (12). Baseline plasma samples were collected at the time of study enrollment.…”

“…The A5208/OCTANE trials were designed to compare protease inhibitor-based therapy using lopinavir/ritonavir (LPV/r) with NVP-based therapy in ART-naive women with or without prior sdNVP. A5208 trial 1, which will be the focus of this report, showed that LPV/r + TDF and emtricitabine (FTC) was superior to NVP + TDF/FTC (P = 0.001) for initial therapy of women with prior sdNVP ≥6 mo earlier and a CD4 cell count <200 cells/mm 3 (12). Standard genotype analysis of stored pretherapy plasma samples revealed NVP resistance mutations in 13% of women in the NVP arm, 73% of whom experienced the primary study endpoint of virological failure or death.…”

The 14th Bangkok International Symposium on HIV Medicine

“…The WHO guidelines, however, provide a second option of zidovudine with single-dose nevirapine (AZT plus sd-NVP), stating that both options have advantages and disadvantages in terms of feasibility, acceptability, safety and cost [103]. The Optimal Combination Therapy After Nevirapine Exposure (OCTANE) study showed inferior outcome after NVP-versus protease inhibitor (PI)-based HAART in women exposed to sd-NVP [1]. A Thai feasibility study showed that the transition to HAART for all HIV-infected pregnant women was acceptable and achievable.…”