title: Meta-analysis of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and nevirapine therapy in patients with HIV. INCAS study team.
abstract: OBJECTIVE
  To extend the range of CD4 counts in which a plasma viral load nadir (pVL) <20 copies/ml was known to be predictive of the duration of virologic response. To determine whether baseline pVL is predictive of virologic response during the study periods.
  
  
  METHODS
  A meta-analysis was conducted of the original individual patient data from two randomized controlled trials comparing zidovudine (ZDV)/didanosine (ddI) with ZDV/ddI/nevirapine (NVP).
  
  
  RESULTS
  In total, 87 patients received ZDV/ddI and 83 received ZDV/ddI/NVP. Study subjects on triple therapy with baseline pVL <100,000 copies/ml were more likely to achieve a pVL <400 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those with baseline pVL > 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir <20 copies/ml and between 21 and 400 copies/ml were .04 (p = .0001) and .56 (p = .26), respectively, compared with patients with a pVL nadir >400 copies/ml.
  
  
  CONCLUSIONS
  We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.
authors.affiliation: Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. jraboud@hivnet.ubc.ca
authors.forename: J M
authors.initials: JM
authors.lastname: Raboud
authors.forename: S
authors.initials: S
authors.lastname: Rae
authors.forename: S
authors.initials: S
authors.lastname: Vella
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: R
authors.initials: R
authors.lastname: Bucciardini
authors.forename: V
authors.initials: V
authors.lastname: Fragola
authors.forename: D
authors.initials: D
authors.lastname: Ricciardulli
authors.forename: J S
authors.initials: JS
authors.lastname: Montaner
mesh_terms: D000328:Adult; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015215:Zidovudine; D019829:Nevirapine; D016049:Didanosine