Journal
HIV MEDICINE
Volume 14, Issue 5, Pages 284-292Publisher
WILEY
DOI: 10.1111/hiv.12004
Keywords
antiretroviral drug resistance; antiretroviral therapy; baseline viral load; viral suppression
Categories
Funding
- Janssen to MetaVirology Ltd
- European AIDS Treatment Network (NEAT)
- European Union [LSHP-CT-2006-037570]
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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<50copies/mL at week 48 was 81.5% (5322 of 6814) for patients with baseline HIV-1 RNA <100000, vs. 72.6% (3949 of 5556) for patients with HIV-1 RNA>100000copies/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) 5.98.9%; P<0.001]. This difference was consistent in trials of NNRTI-based treatments (difference=6.9%; 95% CI 4.39.6%), protease inhibitor-based treatments (difference=8.4%; 95% CI 6.010.8%) and integrase or chemokine (C-C motif) receptor 5 (CCR5)-based treatments (difference=6.0%; 95% CI 2.19.9%) and for trials using TDF/FTC (difference=8.4%; 95% CI 6.010.8%); 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>100000 copies/mL (P<0.001). This difference in efficacy was consistent across trials of different treatment classes and NRTI backbones.
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