title: Efficacy of new antiretroviral drugs in treatment-experienced HIV-infected patients: a systematic review and meta-analysis of recent randomized controlled trials.
abstract: OBJECTIVE
  We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the overall efficacy of new antiretroviral drugs, as well as the factors associated with increased efficacy. We compared CD4 cell count increases associated with chemokine (C-C motif) receptor 5 (CCR5) inhibitors or other new drugs, using indirect comparison.
  
  
  METHODS
  We included RCTs published in 2003-2010 that assessed the 48-week immunological and virological efficacy of adding new antiretroviral drugs vs. placebo to optimized background therapy (OBT) in treatment-experienced subjects. These drugs included maraviroc, vicriviroc, enfuvirtide, raltegravir, etravirine, tipranavir and darunavir. We collected baseline descriptive characteristics, CD4 cell count changes and virological suppression proportions (percentage with HIV RNA <50 HIV-1 RNA copies/mL).
  
  
  RESULTS
  We identified 10 studies which included a total of 6401 patients. New drugs were associated with increased virological suppression (pooled odds ratio 2.97) and larger CD4 count increases (pooled nonstandardized difference 39 cells/μL) compared with placebo. OBT genotypic sensitivity scores (GSSs) were also associated with larger differences in virological suppression (P<0.001 for GSS=0,≤1 and ≤2) and CD4 cell count increase (GSS=0, P<0.001; GSS ≤1, P=0.002; GSS ≤2, P=0.015) between the two groups. CCR5 inhibitors were not associated with significant gains in CD4 cell counts (P=0.22) compared with other new drugs.
  
  
  CONCLUSIONS
  Our study confirmed the overall immunological and virological efficacy of new antiretroviral drugs in treatment-experienced patients, compared with placebo. The main predictive factor for efficacy was the number of fully active drugs. CCR5 inhibitors did not increase CD4 cell count to a greater extent than other new drugs.
authors: Department of Infectious Diseases, Hospital of Tourcoing, Tourcoing, France. marie.pichenot@hotmail.fr
authors: M
authors: M
authors: Pichenot
authors: S
authors: S
authors: Deuffic-Burban
authors: L
authors: L
authors: Cuzin
authors: Y
authors: Y
authors: Yazdanpanah
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists