Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials.
HIV
dolutegravir
individual-participant data meta-analysis
monotherapy
proviral DNA
randomized trial
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
24
11
2021
accepted:
03
03
2022
entrez:
26
5
2022
pubmed:
27
5
2022
medline:
27
5
2022
Statut:
epublish
Résumé
Dolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials. We searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48. Among 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%-2%; Our study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir.
Sections du résumé
Background
UNASSIGNED
Dolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials.
Methods
UNASSIGNED
We searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48.
Results
UNASSIGNED
Among 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%-2%;
Conclusions
UNASSIGNED
Our study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir.
Identifiants
pubmed: 35615294
doi: 10.1093/ofid/ofac107
pii: ofac107
pmc: PMC9125303
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofac107Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Références
N Engl J Med. 2020 Mar 19;382(12):1112-1123
pubmed: 32130809
Clin Infect Dis. 2019 Oct 15;69(9):1489-1497
pubmed: 30601950
AIDS Res Ther. 2021 May 3;18(1):26
pubmed: 33941212
Open Forum Infect Dis. 2019 Mar 22;6(3):ofz051
pubmed: 30949521
J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19490
pubmed: 25393999
Clin Infect Dis. 2017 Nov 29;65(12):2112-2118
pubmed: 29020293
Lancet Infect Dis. 2015 Jul;15(7):785-92
pubmed: 26062880
J Antimicrob Chemother. 2018 Jul 1;73(7):1965-1971
pubmed: 29608685
N Engl J Med. 1998 Oct 29;339(18):1269-76
pubmed: 9791142
Stat Methods Med Res. 2021 Feb;30(2):376-395
pubmed: 32955403
HIV Med. 2020 Nov;21(10):617-624
pubmed: 32885559
N Engl J Med. 2020 Mar 19;382(12):1124-1135
pubmed: 32130806
Clin Infect Dis. 2020 Nov 5;71(8):1920-1929
pubmed: 31905383
Ann Intern Med. 2021 Jun;174(6):758-767
pubmed: 33721521
Stat Med. 2005 May 15;24(9):1307-19
pubmed: 15685717
Clin Pharmacokinet. 2013 Nov;52(11):981-94
pubmed: 23824675
J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):515-9
pubmed: 26262777
Clin Infect Dis. 2019 Oct 15;69(9):1498-1505
pubmed: 30601976
Lancet HIV. 2017 Dec;4(12):e547-e554
pubmed: 29107562
Antivir Ther. 2007;12(8):1157-64
pubmed: 18240856
Lancet. 2019 Jan 12;393(10167):143-155
pubmed: 30420123
J Antimicrob Chemother. 2021 May 12;76(6):1564-1572
pubmed: 33724373
PLoS One. 2017 Feb 13;12(2):e0171611
pubmed: 28192453
J Antimicrob Chemother. 2017 Oct 1;72(10):2831-2836
pubmed: 29091218
J Antimicrob Chemother. 2020 Mar 1;75(3):675-680
pubmed: 31800056
JAMA. 2020 Oct 27;324(16):1651-1669
pubmed: 33052386
J Antimicrob Chemother. 2019 Oct 1;74(10):3030-3034
pubmed: 31314108
N Engl J Med. 1998 Oct 29;339(18):1261-8
pubmed: 9791141
Lancet Infect Dis. 2015 Jul;15(7):775-84
pubmed: 26062881
J Antimicrob Chemother. 2021 Feb 11;76(3):738-742
pubmed: 33200210
Lancet Infect Dis. 2013 Nov;13(11):927-35
pubmed: 24074642
HIV Med. 2019 Jan;20(1):63-68
pubmed: 30270543
HIV Med. 2018 Jun 22;:
pubmed: 29932298
Virologie (Montrouge). 2019 Aug 1;23(4):241-249
pubmed: 31414661
J Antimicrob Chemother. 2017 Apr 1;72(4):1163-1171
pubmed: 28093483
Lancet. 2013 Aug 24;382(9893):700-8
pubmed: 23830355
N Engl J Med. 2019 Aug 29;381(9):803-815
pubmed: 31339677
Lancet. 2018 Mar 3;391(10123):839-849
pubmed: 29310899
JAMA. 2015 Apr 28;313(16):1657-65
pubmed: 25919529
Open Forum Infect Dis. 2021 Jul 01;8(7):ofab316
pubmed: 34307726
J Infect Dis. 2011 Oct 15;204(8):1211-6
pubmed: 21917894
Clin Microbiol Rev. 2016 Oct;29(4):859-80
pubmed: 27559075
N Engl J Med. 2021 Jul 22;385(4):330-341
pubmed: 34289276
BMC Infect Dis. 2017 Mar 16;17(1):215
pubmed: 28302065
J Antimicrob Chemother. 2013 May;68(5):1169-78
pubmed: 23335199
HIV Med. 2016 Feb;17(2):83-8
pubmed: 26548563