title: 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.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut de Recherche pour le Développement and Department of International Health, University of Montpellier (UMR 145), Montpellier, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Laurent
authors.forename: Charles
authors.initials: C
authors.lastname: Kouanfack
authors.forename: Sinata
authors.initials: S
authors.lastname: Koulla-Shiro
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nkoué
authors.forename: Anke
authors.initials: A
authors.lastname: Bourgeois
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Bernadette
authors.initials: B
authors.lastname: Lactuock
authors.forename: Viviane
authors.initials: V
authors.lastname: Nzeusseu
authors.forename: Rose
authors.initials: R
authors.lastname: Mougnutou
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Florian
authors.initials: F
authors.lastname: Liégeois
authors.forename: Eric
authors.initials: E
authors.lastname: Nerrienet
authors.forename: Michèle
authors.initials: M
authors.lastname: Tardy
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
authors.forename: Isabelle
authors.initials: I
authors.lastname: Andrieux-Meyer
authors.forename: Léopold
authors.initials: L
authors.lastname: Zekeng
authors.forename: Michel
authors.initials: M
authors.lastname: Kazatchkine
authors.forename: Eitel
authors.initials: E
authors.lastname: Mpoudi-Ngolé
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002163:Cameroon; D003906:Developing Countries; D018450:Disease Progression; D004338:Drug Combinations; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D004338:Drug Combinations; D016568:Drugs, Generic; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine