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

J Acquir Immune Defic Syndr. 1999 Nov 1;22(3):260-6. doi: 10.1097/00126334-199911010-00007.

Abstract

Objectives: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Didanosine / administration & dosage
  • Didanosine / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nevirapine / administration & dosage
  • Nevirapine / therapeutic use*
  • Proportional Hazards Models
  • Viral Load
  • Zidovudine / administration & dosage
  • Zidovudine / therapeutic use*

Substances

  • Zidovudine
  • Nevirapine
  • Didanosine