Meta-analysis of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and nevirapine therapy in patients with HIV

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 vir ologic response. To determine whether baseline pVL is predictive of virolog ic response during the study periods. Methods: A meta-analysis was conducted of the original individual patient d ata from two randomized controlled trials comparing zidovudine (ZDV)/didano sine (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 gVL <100,000 copies/ml wer e more likely to achieve a pVL <300 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those wi th baseline pVL >100,000 copies/ml. Among triple therapy patients, the rela tive risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log(10) copies/ml, p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure asso ciated 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 nadi r <20 copies/ml is important for maintaining virologic suppression. In part icular, we have demonstrated that a pVL nadir <20 copies/ml is at least fiv efold 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.