title: Antiretroviral therapy for initial human immunodeficiency virus/AIDS treatment: critical appraisal of the evidence from over 100 randomized trials and 400 systematic reviews and meta-analyses.
abstract: There have been over 100 randomized clinical trials (RCTs) of diverse regimens of antiretroviral therapy for treatment-naïve human immunodeficiency virus-positive 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 in interpreting multiple trials in this population. We specifically examine the network geometry of the clinical trial comparisons, the predominance 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.
authors.affiliation: School of Population & Public Health, University of British Columbia, Vancouver, BC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Kanters
authors.forename: E J
authors.initials: EJ
authors.lastname: Mills
authors.forename: K
authors.initials: K
authors.lastname: Thorlund
authors.forename: H C
authors.initials: HC
authors.lastname: Bucher
authors.forename: J P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012196:Review Literature as Topic
chemical_list: D044966:Anti-Retroviral Agents
keywords: Adverse events; HIV/AIDS; antiretroviral therapy; class effects; meta-analysis; network meta-analysis; non-inferiority; randomized clinical trials; systematic reviews