Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance

J Clin Virol. 2005 May;33(1):75-8. doi: 10.1016/j.jcv.2004.11.012.

Abstract

Background: In HIV-infected patients on first-line antiretroviral therapy, the significance of intermittent viremia and their relationship with drug resistance remain unclear.

Objective: To study the virological characteristics of intermittent viremia (IV) and the association between IV and later virological failure (VF) in patients on a first-line, PI-containing therapy.

Study design: Antiretroviral-naive patients were enrolled in the APROVIR substudy of the prospective, multicenter APROCO cohort at the time they initiated a PI-containing therapy and were followed-up at month 1 and every 2 months. IV was defined as plasma HIV-1 RNA > 500 copies/ml on a single specimen. VF were defined as: (1) viral rebound on two consecutive plasma specimens with HIV-1 RNA > 500 copies/ml after an initial response below 500 copies/ml, or (2) persistence of plasma HIV-1 RNA> or =500 copies/ml during the first year of follow-up. Genotypic resistance analysis was performed at baseline and at the time of IV. PI plasma concentrations were determined at the time of IV.

Results: IV was found in 20/219 patients in a 2 years follow-up. The occurrence of IV in the first year of therapy was associated with a higher risk of virological failure during the second year (p = 0.03). Genotypic resistance at the time of IV was found in only 4/16 patients and was not predictive of a subsequent virological failure. PI plasma levels suggested lack of adherence in 50% of patients with IV.

Conclusion: The occurrence of IV > 500 copies/ml among patients on first-line, PI-containing ART is suggestive of a lack of adherence rather than the selection of resistant variants and should lead to an intensification of adherence monitoring in order to reduce the risk of subsequent VF.

Publication types

  • Clinical Trial

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Patient Compliance
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Viral Load
  • Viremia / drug therapy
  • Viremia / virology*

Substances

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