Success and failure of initial antiretroviral therapy in adults

BACKGROUND: We updated a prior systematic review of initial antiretroviral therapy (ART) efficacy through week 144. MATERIALS AND METHODS: Studies (1994 to July 2017) were drawn from PubMed, ClinicalTrials.gov, Cochrane Library, and major conferences; design, eligibility, patient, and ART data were abstracted. Outcomes are expressed as group size-weighted means. Mixed-effects meta-regression was used to identify sources of efficacy heterogeneity. RESULTS: Within 354 groups (181 studies, 77 999 participants), principal backbones were tenofovir-emtricitabine (TDF/TAF-FTC) (44.2%), thymidine-based (27.7%), and abacavir-lamivudine (9.7%). Principal anchors were non-nucleoside analog (49.7%), boosted protease inhibitor (28.1%), and integrase inhibitor (INSTI; 11.5%). Mean intention-to-treat efficacy (RNA <50 copies/ml) was 71.3%, 63.5% (145 groups), and 61.8% (48 groups) at weeks 48, 96, and 144, respectively (for post-2010 studies, 83.8%, 79.9%, and 77.1%). TDF/TAF-FTC and INSTI were independent predictors of greater efficacy at weeks 48, 96, and 144. Additional independent predictors at week 48 were pre-ART resistance genotyping, higher baseline CD4 cell count, and once-daily ART. Fewer pills per day predicted greater efficacy at weeks 96 and 144. Phase 4 studies yielded progressively inferior efficacy than phase 3 studies (difference 5.1% at week 48, 15.8% at week 144). Cessation through week 144 overall (29.4%) and for adverse events (8.9%) declined over time, but cessation for virological failure (5.2%) did not. CONCLUSIONS: Initial ART efficacy continues to improve, but more than 20% of post-2010 patients failed over 3 years. Real-world efficacy is lower than in phase 3 trials. Guidelines should list non-INSTI-based initial ART as nonpreferred. Strategies are needed to improve access to pre-ART genotyping and to increase early initiation of once-daily ART.