Header

UZH-Logo

Maintenance Infos

Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials


Fournier, Anna L; Hocqueloux, Laurent; Braun, Dominique L; Metzner, Karin J; Kouyos, Roger D; Raffi, François; Briant, Anaïs R; Martinez, Esteban; De Lazzari, Elisa; Negredo, Eugenia; Rijnders, Bart; Rokx, Casper; Günthard, Huldrych F; Parienti, Jean-Jacques (2022). Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials. Open Forum Infectious Diseases, 9(6):ofac107.

Abstract

Background

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

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

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%; P = .02; I$^{2}$ = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60-16.65), CD4 T cells nadir <350/mm$^{3}$ (aHR, 12.10; 95% CI, 3.92-37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68-6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/10$^{6}$ peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99-7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I$^{2}$ = 80.2%; P for interaction = .02).

Conclusions

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.

Abstract

Background

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

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

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%; P = .02; I$^{2}$ = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60-16.65), CD4 T cells nadir <350/mm$^{3}$ (aHR, 12.10; 95% CI, 3.92-37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68-6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/10$^{6}$ peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99-7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I$^{2}$ = 80.2%; P for interaction = .02).

Conclusions

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.

Statistics

Citations

Dimensions.ai Metrics
6 citations in Web of Science®
6 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

8 downloads since deposited on 17 Nov 2022
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Health Sciences > Infectious Diseases
Language:English
Date:1 June 2022
Deposited On:17 Nov 2022 08:07
Last Modified:29 Jan 2024 02:48
Publisher:Oxford University Press
ISSN:2328-8957
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ofid/ofac107
PubMed ID:35615294
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)