Efficacy, tolerability and virological consequences of long-term use of unboosted atazanavir plus 2 NRTIs in HIV-infected patients

Curr HIV Res. 2014;12(5):339-46. doi: 10.2174/1570162x12666140807151616.

Abstract

Purpose: Switch to unboosted atazanavir (ATV) is an attractive option due to convenience and tolerability in HIV-positive patients. With limited available data we investigated the determinants of long-term efficacy and the consequences of virological failure of unboosted atazanavir-based regimens.

Methods: Retrospective analysis in two Italian large outpatient clinics including demographic, immunovirological, resistance and pharmacokinetic data.

Results: 249 patients receiving atazanavir (400 mg once-daily) plus 2 NRTIs were included; 163 were males (65.5%) and median age was 47 years (42-51.5). Median CD4+ T-cell count was 396/uL (261-583); 146 (58.6%) presented a viral load < 50 copies/mL. Over a median follow up of 157 weeks (106-203) 193 patients (77.5%) were still on treatment with 10 (4%) and 2 (0.8%) stopping for virological failure or toxicity, respectively. Ten patients with virological failure presented newly selected resistance associated mutations (RAMs) for NRTIs (2/10) or ATV (4/10, one I50L). Total cholesterol and triglycerides showed significant decreases at 48 [-4 mg/dL and -41 mg/dL] and 96 weeks [-14 mg/dL and -54 mg/dL] as compared to baseline. At multivariate analysis a genotypic sensitivity score ≤ 1, atazanavir RAMs > 1 and suboptimal adherence were independently associated with virological failure; in lamivudine/emtricitabine-treated patients the presence of M184V (without other NRTI RAMs) was not associated with virological failure.

Conclusion: Unboosted-atazanavir containing regimens were efficacious (with uncommon virological failures) and well-tolerated (with improvements in lipid profile over time) treatments in HIV-positive patients. Isolated M184V in lamivudine/emtricitabine recipients was not associated with higher failure rates supporting the use of functional ATV-based dual therapies as maintenance strategies.

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Atazanavir Sulfate
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral / genetics
  • Drug Substitution
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / therapeutic use*
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • RNA, Viral / genetics
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Viral Load

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Atazanavir Sulfate