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


  • This study was presented in part at the World AIDS Conference in Washington DC, USA, July 2012 (Abstract TUPE085).

Correspondence: Dr Christoph Stephan, Johann Wolfgang Goethe University Hospital, Medical Department no.2/Infectious Diseases Unit, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Tel: +49 69 6301 7680; fax: +49 69 6301 5712; e-mail:



Individual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy.


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.


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).


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.