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.
Antiretroviral therapy
First-line
HIV
Network meta-analysis
Journal
EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
01
07
2020
revised:
17
09
2020
accepted:
18
09
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
10
12
2020
Statut:
epublish
Résumé
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. 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. 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). 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. WHO.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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
BACKGROUND
WHO.
Identifiants
pubmed: 33294805
doi: 10.1016/j.eclinm.2020.100573
pii: S2589-5370(20)30317-5
pmc: PMC7700905
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100573Subventions
Organisme : World Health Organization
ID : 001
Pays : International
Organisme : NICHD NIH HHS
ID : K23 HD088230
Pays : United States
Informations de copyright
© 2020 Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
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.
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