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AIDS. 2018 Nov 19. doi: 10.1097/QAD.0000000000002077. [Epub ahead of print]

Success and failure of initial antiretroviral therapy in adults: an updated systematic review of 77,999 subjects from 1994 to 2017.

Author information

1
Centre for Applied Medical Research, St Vincent's Hospital.
2
University of New South Wales, Sydney, Australia.

Abstract

BACKGROUND:

We updated a prior systematic review of initial ART efficacy through Week 144.

MATERIALS AND METHODS:

Studies (1994-July 2017) were drawn from PubMed, ClinicalTrials.gov, Cochrane Library, and major conferences; design, eligibility, subject 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 subjects), principal backbones were tenofovir-emtricitabine (TDF/TAF-FTC) (44.2%), thymidine-based (27.7%), and abacavir-lamivudine (9.7%). Principal anchors were non-nucleoside analogue (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 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 >20% of post-2010 subjects failed over 3 years. Real-world efficacy is lower than in phase-3 trials. Guidelines should list non-INSTI-based initial ART as non-preferred. Strategies are needed to improve access to pre-ART genotyping and to increase early initiation of once-daily ART.

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