Antiretroviral therapy for initial HIV/AIDS treatment: Critical appraisal of the evidence from over 100 randomized trials and 400 systematic reviews and meta-analyses

There have been over 100 randomized clinical trials of diverse regimens of antiretroviral therapy (ART) for treatment-naive HIV+ patients. A further 400 systematic reviews and meta-analyses are informed by these trials. There are, however, difficulties in using systematic reviews and meta-analyses of this clinical evidence to inform guidelines and clinical practice. Several issues can make the interpretation of comparative effectiveness challenging. In this article, we review the key challenges of interpreting multiple trials in this population. We specifically examine the network geometry of the clinical trial comparisons, the dominance of non-inferiority trial designs, issues related to potential class-effects, heterogeneous documentation of adverse events, and a relative lack of RCTs that reflect specific current clinical guideline recommendations. We conclude with recommendations for future clinical trials and meta-analyses. This article is protected by copyright. All rights reserved.