Antiretroviral Therapies in Women After Single-Dose Nevirapine Exposure

N Engl J Med. 2010 Oct 14;363(16):1499-509. doi: 10.1056/NEJMoa0906626.

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.).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-Retroviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV Infections / transmission
  • HIV-1*
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Kaplan-Meier Estimate
  • Linear Models
  • Lopinavir
  • Nevirapine / administration & dosage*
  • Organophosphonates / therapeutic use
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pyrimidinones / therapeutic use
  • Ritonavir / therapeutic use
  • Statistics, Nonparametric
  • Tenofovir
  • Treatment Failure
  • Young Adult

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Organophosphonates
  • Pyrimidinones
  • Deoxycytidine
  • Lopinavir
  • Nevirapine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00089505