title: Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy.
abstract: OBJECTIVE
  To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.
  
  
  METHODS
  Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.
  
  
  METHODS
  Patients with any stage of HIV infection who had not received antiretroviral therapy.
  
  
  METHODS
  Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
  
  
  METHODS
  Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.
  
  
  RESULTS
  54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.
  
  
  CONCLUSIONS
  Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.
authors.affiliation: Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham B15 2TT. r.e.jordan@bham.ac.uk
authors.forename: Rachel
authors.initials: R
authors.lastname: Jordan
authors.forename: Lisa
authors.initials: L
authors.lastname: Gold
authors.forename: Carole
authors.initials: C
authors.lastname: Cummins
authors.forename: Chris
authors.initials: C
authors.lastname: Hyde
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic / Q000592:standards; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents