Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial

Lancet. 2004 Jul;364(9428):29-34. doi: 10.1016/S0140-6736(04)16586-0.

Abstract

Background: Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine.

Methods: 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis.

Findings: At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine.

Interpretation: Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Anti-Retroviral Agents / adverse effects
  • CD4 Lymphocyte Count
  • Cameroon
  • Developing Countries*
  • Disease Progression
  • Drug Combinations
  • Drugs, Generic / administration & dosage*
  • Drugs, Generic / adverse effects
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1* / isolation & purification
  • Humans
  • Lamivudine / administration & dosage
  • Lamivudine / adverse effects
  • Male
  • Nevirapine / administration & dosage
  • Nevirapine / adverse effects
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Stavudine / administration & dosage
  • Stavudine / adverse effects
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • Drug Combinations
  • Drugs, Generic
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Nevirapine
  • Stavudine