Mechanism of virologic failure after substitution of a protease inhibitor by nevirapine in patients with suppressed plasma HIV-1 RNA

J Acquir Immune Defic Syndr. 2001 Dec 1;28(4):309-12. doi: 10.1097/00126334-200112010-00001.

Abstract

A prospective study was set up to evaluate the emergence of HIV-1 resistance after a switch from an effective protease inhibitor (PI)-containing regimen to a multitherapy regimen including nevirapine (NVP). After 6 months with an undetectable viral load under a PI-containing regimen, the patients were switched to NVP with conservation of the associated nucleoside reverse transcriptase inhibitors (NRTIs). Patients were followed-up at 1 month and then every 3 months after switching therapy. Nucleotide sequence analysis of the pol gene was performed at the first points of virologic failure. Thirty-four patients were included. The NRTI-naive group (22 patients) had begun antiretroviral therapy with a PI-containing regimen, whereas 12 patients (experienced group) had been previously treated by nucleoside mono-and/or dual therapy. After a median follow-up of 40 weeks, no patient of the naive group, versus 41% of the experienced group, developed a virologic failure after the change toward NVP ( p =.003). The virologic failures were associated with the appearance of NNRTI-resistant mutations. All rebound mutants also presented NRTI-resistance mutations. These results are consistent with a higher risk of virologic failure after a switch to an NNRTI in patients with prior suboptimal treatment and suggest the hypothesis that archived resistant viruses may facilitate the emergence of NNRTI resistance.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Endopeptidases / genetics
  • Genes, pol
  • Genotype
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Mutation
  • Nevirapine / therapeutic use*
  • Prospective Studies
  • Protease Inhibitors / therapeutic use*
  • RNA, Viral / blood*
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Time Factors
  • Viral Load

Substances

  • Anti-HIV Agents
  • Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • HIV Reverse Transcriptase
  • Endopeptidases