Comparative Efficacy, Tolerability and Safety of Dolutegravir and Efavirenz 400mg Among Antiretroviral Therapies for First-line HIV Treatment: A Systematic Literature Review and Network Meta-analysis

Overview

Journal EClinicalMedicine

Specialty General Medicine

Date 2020 Dec 9

PMID 33294805

Citations 41

Authors

Steve Kanters

Marco Vitoria

Michael Zoratti

Meg Doherty

Martina Penazzato

Ajay Rangaraj

Nathan Ford

Kristian Thorlund

Prof Aslam H Anis

Mohammad Ehsanul Karim

Lynne Mofenson

Rebecca Zash

Alexandra Calmy

Tamara Kredo

Nick Bansback

Affiliations

Soon will be listed here.

Abstract

Background: To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral therapy (ART) regimens.

Methods: We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework.

Findings: We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio [OR]: 1·94; 95% credible interval [CrI]: 1·48-2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04-0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48-0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50-0·92).

Interpretation: The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable.

Funding: WHO.

Citing Articles

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PMID: 39302585 DOI: 10.1007/s40261-024-01390-y.

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