Increasing rate of TAMs and etravirine resistance in HIV-1-infected adults between 12 and 24 months of treatment: the VOLTART cohort study in Côte d'Ivoire, West Africa

J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):211-9. doi: 10.1097/QAI.0b013e3182a009e4.

Abstract

Background: In sub-Saharan Africa, most HIV-infected patients receive antiretroviral therapy (ART) without virological monitoring. Longitudinal data on secondary resistance are rare.

Methods: We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had plasma HIV-1 RNA viral load (VL) tests at months 12 (M12) and 24 (M24) after ART initiation and HIV-1 resistance genotype tests if VL was detectable (≥300 copies/mL).

Results: Overall, 1573 patients initiated ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M12 and M24, 944 and 844 patients, respectively, remained in active follow-up. Among them, 25% (M12) and 27% (M24) had detectable VLs and 12% (M12) and 19% (M24) had virus resistant to at least 1 antiretroviral drug, accounting for 54% (M12) and 75% (M24) of patients with detectable VLs. Among the resistant strains, 95% (M12) and 97% (M24) were resistant to lamivudine/emtricitabine, efavirenz, and/or nevirapine, the frequency of thymidine analog mutations increased from 8.1% (M12) to 14.7% (M24) and etravirine resistance increased from 13.5% (M12) to 24.5% (M24).

Conclusions: Of the patients with detectable VLs at M24, 25% still did not harbor resistant virus. Preventing mutations from emerging with adherence reinforcement in patients with detectable VLs remains important beyond M24. Switching therapy early in patients with resistance to 3 TC/FTC and/or to nonnucleoside reverse transcriptase inhibitors to prevent extended resistance to nucleoside reverse transcriptase inhibitors and etravirine resistance from occurring is also a major challenge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Cote d'Ivoire
  • Drug Monitoring / methods
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Mutation*
  • Nitriles
  • Prospective Studies
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacology*
  • Pyridazines / therapeutic use
  • Pyrimidines
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacology
  • Time Factors
  • Viral Load

Substances

  • Anti-HIV Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • etravirine
  • Thymidine