Antiretroviral activity and safety of abacavir in combination with selected HIV-1 protease inhibitors in therapy-naive HIV-1-infected adults

Antivir Ther. 2001 Jun;6(2):105-14.

Abstract

Objective: To assess antiretroviral efficacy and safety of abacavir in combination with selected HIV-1 protease inhibitors.

Design: A 48-week, open-label study.

Materials and methods: Eighty-two antiretroviral naive HIV-1-infected adults (CD4 cell count > or = 100 cells/mm3, plasma HIV-1 RNA > or = 5,000 copies/ml) were randomly assigned to receive abacavir (300 mg twice daily) in combination with standard doses of one of five protease inhibitors: indinavir, saquinavir soft-gel, ritonavir, nelfinavir or amprenavir. Adults who met protocol-defined switch criteria at or after week 8 could modify their randomized therapy. Antiretroviral activity was assessed by the proportion of subjects with plasma HIV-1 RNA < or = 400 and < or = 50 copies/ml, and by changes in plasma HIV-1 RNA levels and CD4 cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities.

Results: At week 48, the proportion of subjects in the indinavir, saquinavir, ritonavir, nelfinavir and amprenavir groups with plasma HIV-1 RNA < or = 400 copies/ml was 53, 50, 50, 41 and 56%, respectively, and the proportion with HIV-1 RNA < or = 50 copies/ml was 47, 56, 50, 47, and 44%, respectively (by intent-to-treat analysis). Median reductions from baseline in plasma HIV-1 RNA for each group ranged from 1.7 to 2.4 log10 copies/ml. The median CD4 cell count increase from baseline was 195, 131, 116, 136 and 259 cells/mm3 in the indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir groups, respectively. Overall, the most common adverse events attributed to study drugs were diarrhoea, nausea, malaise/fatigue, headache and perioral paresthesia. The frequency of treatment-limiting adverse events did not differ between groups.

Conclusions: Abacavir is safe and effective when used in combination with a protease inhibitor.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / drug effects
  • Dideoxynucleosides / administration & dosage*
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / administration & dosage*
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Male
  • RNA, Viral / blood
  • Time Factors

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • HIV Protease Inhibitors
  • RNA, Viral
  • abacavir