PMID- 33294805 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220418 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 28 DP - 2020 Nov TI - 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. PG - 100573 LID - 10.1016/j.eclinm.2020.100573 [doi] LID - 100573 AB - 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. CI - (c) 2020 Published by Elsevier Ltd. FAU - Kanters, Steve AU - Kanters S AD - School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Vitoria, Marco AU - Vitoria M AD - Department of HIV/AIDS, WHO, Geneva, Switzerland. FAU - Zoratti, Michael AU - Zoratti M AD - Departments of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada. FAU - Doherty, Meg AU - Doherty M AD - Department of HIV/AIDS, WHO, Geneva, Switzerland. FAU - Penazzato, Martina AU - Penazzato M AD - Department of HIV/AIDS, WHO, Geneva, Switzerland. FAU - Rangaraj, Ajay AU - Rangaraj A AD - Department of HIV/AIDS, WHO, Geneva, Switzerland. FAU - Ford, Nathan AU - Ford N AD - Department of HIV/AIDS, WHO, Geneva, Switzerland. FAU - Thorlund, Kristian AU - Thorlund K AD - Departments of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada. FAU - Anis, Prof Aslam H AU - Anis PAH AD - School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. AD - Centre for Health Evaluation and Outcome Science, University of British Columbia, Vancouver, Canada. FAU - Karim, Mohammad Ehsanul AU - Karim ME AD - School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. AD - Centre for Health Evaluation and Outcome Science, University of British Columbia, Vancouver, Canada. FAU - Mofenson, Lynne AU - Mofenson L AD - Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA. FAU - Zash, Rebecca AU - Zash R AD - Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, USA. AD - Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana. FAU - Calmy, Alexandra AU - Calmy A AD - HIV/AIDS Unit, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland. FAU - Kredo, Tamara AU - Kredo T AD - South African Medical Research Council, Cape Town, South Africa. FAU - Bansback, Nick AU - Bansback N AD - School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. AD - Centre for Health Evaluation and Outcome Science, University of British Columbia, Vancouver, Canada. LA - eng GR - 001/WHO_/World Health Organization/International GR - K23 HD088230/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20201016 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC7700905 OTO - NOTNLM OT - Antiretroviral therapy OT - First-line OT - HIV OT - Network meta-analysis COIS- Dr. Karim reports grants from Michael Smith Foundation for Health Research, grants from Natural Sciences and Engineering Research Council, grants from BC SUPPORT Unit, grants from Canadian Institutes of Health Research, personal fees from Biogen Inc., outside the submitted work. Dr. Alexandra reports grants from Unrestriceted Educational Grant (for the Unit) by MSD and Gilead Sciences, grants from Financial support by Gilead Sciences, AbbVie, MSD, ViiV Healthcare and Janssen Cilag for the day hospital, outside the submitted work. All other authors have nothing to declare. EDAT- 2020/12/10 06:00 MHDA- 2020/12/10 06:01 PMCR- 2020/10/16 CRDT- 2020/12/09 06:16 PHST- 2020/07/01 00:00 [received] PHST- 2020/09/17 00:00 [revised] PHST- 2020/09/18 00:00 [accepted] PHST- 2020/12/09 06:16 [entrez] PHST- 2020/12/10 06:00 [pubmed] PHST- 2020/12/10 06:01 [medline] PHST- 2020/10/16 00:00 [pmc-release] AID - S2589-5370(20)30317-5 [pii] AID - 100573 [pii] AID - 10.1016/j.eclinm.2020.100573 [doi] PST - epublish SO - EClinicalMedicine. 2020 Oct 16;28:100573. doi: 10.1016/j.eclinm.2020.100573. eCollection 2020 Nov.