Efficacy and safety of ritonavir-boosted dual protease inhibitor therapy in antiretroviral-naive HIV-1-infected patients: the 2IP ANRS 127 study

J Antimicrob Chemother. 2009 Jul;64(1):118-25. doi: 10.1093/jac/dkp146. Epub 2009 May 6.

Abstract

Objectives: We evaluate the efficacy and tolerability of ritonavir-boosted dual protease inhibitor as a nucleoside reverse transcriptase inhibitor-sparing regimen in a prospective open-label randomized pilot trial in antiretroviral-naive patients.

Methods: Thirty patients received fosamprenavir/atazanavir/ritonavir (Group 1) and 31 patients received saquinavir/atazanavir/ritonavir (Group 2). The primary endpoint for efficacy was the rate of early virological success, defined as plasma viral load <50 copies/mL at week 16. The study is registered with ClinicalTrials.gov (NCT00122603).

Results: At baseline, median (range) viral load was 4.8 log(10) copies/mL (4.0-5.7) and the median CD4 cell count was 271/mm(3) (197-740). Viral load was <50 copies/mL in 12/30 patients [40%, 95% confidence interval (CI) 23%-58%] and 13/31 patients (42%, 95% CI 25%-59%) at week 16 in Groups 1 and 2, respectively. Patients with failing regimens (viral load >or=400 copies/mL at week 16 or >or=50 copies/mL at week 24) were switched to a standard antiretroviral regimen. At week 48, by an intention-to-treat analysis, 23/30 patients (77%) and 26/31 patients (84%) had plasma HIV-1 RNA <50 copies/mL in Groups 1 and 2, respectively. Four patients discontinued treatment for adverse events, all before week 4. No major changes in the protease gene were detected at treatment failure relative to baseline. Baseline viral load <50 000 copies/mL was the only predictor of virological success at week 16.

Conclusions: Ritonavir-boosted dual protease inhibitor regimens targeting only one step of viral replication were insufficient to rapidly suppress plasma HIV RNA to <50 copies/mL in antiretroviral-naive patients with high viral load at baseline.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Asparagine / adverse effects
  • Asparagine / analogs & derivatives
  • Asparagine / therapeutic use
  • Atazanavir Sulfate
  • CD4 Lymphocyte Count
  • Carbamates / adverse effects
  • Carbamates / therapeutic use
  • Female
  • Furans
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use
  • Organophosphates / adverse effects
  • Organophosphates / therapeutic use
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • RNA, Viral / blood
  • Ritonavir / adverse effects*
  • Ritonavir / therapeutic use*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Carbamates
  • Furans
  • HIV Protease Inhibitors
  • Oligopeptides
  • Organophosphates
  • Pyridines
  • Quinolines
  • RNA, Viral
  • Sulfonamides
  • sequinavir
  • Atazanavir Sulfate
  • Asparagine
  • Ritonavir
  • fosamprenavir

Associated data

  • ClinicalTrials.gov/NCT00122603