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Success and failure of initial antiretroviral therapy in adults

an updated systematic review

Carr, Andrewa; Richardson, Robyna; Liu, Zhixinb

doi: 10.1097/QAD.0000000000002077
CLINICAL SCIENCE
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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.

aCentre for Applied Medical Research, St Vincent's Hospital

bUniversity of New South Wales, Sydney, Australia.

Correspondence to Professor Andrew Carr, Centre for Applied Medical Research and HIV, Immunology and Infectious Diseases Unit, St Vincent's Hospital, Victoria St, Darlinghurst NSW 2010, Sydney, Australia. Tel: +61 2 83823359; e-mail: andrew.carr@svha.org.au

Received 27 August, 2018

Accepted 8 October, 2018

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