Effectiveness of dolutegravir-based vs boosted darunavir-based first-line 3-drug regimens in people with HIV with advanced disease: A trial emulation
- PMID: 40089053
- DOI: 10.1016/j.ijid.2025.107883
Effectiveness of dolutegravir-based vs boosted darunavir-based first-line 3-drug regimens in people with HIV with advanced disease: A trial emulation
Abstract
Background: No randomized comparisons exist between dolutegravir (DTG) and boosted-darunavir (DRV/b) for people initiating treatment with advanced HIV.
Methods: Antiretroviral therapy (ART)-naïve people with HIV (PWH) with CD4 < 200 cells/mm3 or AIDS who started a first-line three-drug regimen with DTG or DRV/b were included. The primary outcome was a composite endpoint of newly diagnosed AIDS, serious non-AIDS events (SNAE), death, virological failure (VF), or discontinuation of the anchor drug due to failure or toxicity. A marginal structural Cox regression model was used to estimate the effect of starting DTG vs DRV/b-based regimens.
Results: A total of 1323 advanced ART-naïve PWH were included, 895 starting DTG and 428 DRV/b. The unweighted risks of the composite endpoint by 48 months were 21.1% (95% CI: 18.1; 24.1%) for DTG vs 37.9% (95% CI: 32.7; 43.2%) for DRV/b (P < 0.001). First-line treatment with DTG showed a lower risk of experiencing the composite endpoint than DRV/b (wHR of DTG vs DRV/b 0.47, 95% CI: 0.35; 0.64, P < 0.001).
Conclusion: Under the stated assumptions, this analysis indicates that in ART-naïve PWH with advanced disease, ART initiation with DTG vs DRV/b-based regimens leads to a 50% reduction in the risk of AIDS/SNAE/death/VF/discontinuation. This observed difference is partly explained by discontinuation of the anchor drug.
Keywords: AIDS; ART-naïve; Antiretroviral therapy; Integrase inhibitors; Trial emulation.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RG received consultation fees from Gilead, Viiv, and MSD. AG received consultation fees from Mylan, Gilead, ViiV, Janssen, MSD; Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Mylan, Gilead, ViiV, Janssen, MSD, and Support for attending meetings and/or travel from Gilead, ViiV. SA AG received consultation fees from Pfizer, MSD, ViiV, Gilead. SLC received consultation fees from Gilead, Viiv, Janssen and MSD.SN received consultation fees from Gilead Sciences; ViiV Healthcare; Merck Sharp & Dohme; Jannsen Cilag. CP received consultation fees from Gilead and Janssen. VM received consultation fees from Gilead and Viiv. AA received grants/research supports from Gilead, ViiV; honoraria or consultation fees from Gilead, ViiV, Merck, Roche, Astrazeneca, Pfizer, GSK; participated in company-sponsored speaker's bureau from Gilead, ViiV, Merck. The other authors have nothing to declare.
