title: Impact of baseline HIV-1 RNA levels on initial highly active antiretroviral therapy outcome: a meta-analysis of 12,370 patients in 21 clinical trials*.
abstract: BACKGROUND
  Individual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy.
  
  
  METHODS
  A MEDLINE search identified 21 HIV clinical trials with published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a standardized efficacy endpoint of HIV-1 RNA suppression <50 copies/mL at week 48.
  
  
  RESULTS
  Among 21 clinical trials identified, eight evaluated only nonnucleoside reverse transcriptase inhibitor (NNRTI)-based combinations, eight evaluated only protease inhibitor-based regimens and five compared different treatment classes. Ten of the trials included tenofovir (TDF)/emtricitabine (FTC) as only nucleoside reverse transcriptase inhibitor (NRTI) backbone, in addition but not restricted to abacavir (ABC)/lamivudine (3TC) (n = 7), zidovudine (ZDV)/3TC (n = 4) and stavudine (d4T)/3TC (n = 1). Across trials, the mean percentage of patients achieving HIV-1 RNA < 50 copies/mL at week 48 was 81.5% (5322 of 6814) for patients with baseline HIV-1 RNA < 100 000, vs. 72.6% (3949 of 5556) for patients with HIV-1 RNA > 100 000 copies/mL. In the meta-analysis, the absolute difference in efficacy between low and high HIV-1 RNA subgroups was 7.4% [95% confidence interval (CI) 5.9-8.9%; P < 0.001]. This difference was consistent in trials of NNRTI-based treatments (difference = 6.9%; 95% CI 4.3-9.6%), protease inhibitor-based treatments (difference = 8.4%; 95% CI 6.0-10.8%) and integrase or chemokine (C-C motif) receptor 5 (CCR5)-based treatments (difference = 6.0%; 95% CI 2.1-9.9%) and for trials using TDF/FTC (difference = 8.4%; 95% CI 6.0-10.8%); there was no evidence for heterogeneity of this difference between trials (Cochran's Q test; not significant).
  
  
  CONCLUSIONS
  In this meta-analysis of 21 first-line clinical trials, rates of HIV-1 RNA suppression at week 48 were significantly lower for patients w ith baseline HIV-1 RNA > 100 000 copies/mL (P < 0.001). This difference in efficacy was consistent across trials of different treatment classes and NRTI backbones.
authors.affiliation: Johann Wolfgang Goethe University Hospital, Frankfurt, Germany. c.stephan@em.uni-frankfurt.de
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: W
authors.initials: W
authors.lastname: Sawyer
authors.forename: Y
authors.initials: Y
authors.lastname: van Delft
authors.forename: C
authors.initials: C
authors.lastname: Moecklinghoff
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology*; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors