A Randomized Trial to Compare Dolutegravir Plus Boosted Darunavir Versus Recommended Standard of Care Antiretroviral Regimens in People With HIV-1, Whose First-line Non-nucleoside Reverse Transcriptase Inhibitor Therapy Has Failed: Final 96-week Results of the D2EFT Study

Year: 2025

Type: article

Abstract: BACKGROUND: Longer-term outcome data following second-line antiretroviral therapy initiation in resource-limited settings is limited, especially in regions where genotypic resistance is inaccessible. This analysis evaluated extended efficacy and tolerability data from the D2EFT study. METHODS: D2EFT is a completed, multicenter, phase IIIB/IV, randomized, open-label trial in 14 low- and middle-income countries. People with human immunodeficiency virus (HIV) who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to 1 of ritonavir-boosted darunavir plus 2 nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r), or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC), with or without pre-switch genotyping. Here we report virological suppression at 96 weeks, defined as HIV RNA <50 copies/mL in a modified intention-to-treat population. RESULTS: Between November 2017 and January 2022, 1190 participants were screened, 828 were randomized, and 826 were included in the analysis. At week 96, the proportions of participants with HIV RNA <50 copies/mL were 191/251 (76.1%) in DRV/r + 2NRTIs, 215/251 (85.7%) in DTG + DRV/r, and 231/283 (81.6%) in DTG + TDF/XTC. The treatment differences (95% confidence intervals [CIs]) in proportions achieving virological suppression were 9.6% (2.7, 16.4) in DTG + DRV/r and 9.0% (1.4, 16.6) in DTG + TDF/XTC, compared to DRV/r + 2NRTIs. Intermediate or high-level dolutegravir resistance was identified in 3/27 (13%) of virological failures in individuals taking DTG + TDF/XTC but in no one taking DTG + DRV/r. No darunavir resistance was observed. CONCLUSIONS: After 96 weeks of follow-up, DTG + DRV/r and DTG + TDF/XTC demonstrated virological superiority over DRV/r + 2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG + TDF/XTC, requires ongoing global surveillance.

Source: Clinical Infectious Diseases

DOI: 10.1093/cid/ciaf346

Authors: Phyo Pyae Nyein, Margaret Borok, Nnakelu Eriobu, Richard Kaplan, Nagalingeswaran Kumarasamy, Anchalee Avihingsanon, Marcelo H Losso, Iskandar Azwa, Muhammad Karyana, Sounkalo Dao, Mohamed Cisse, Jaime F Andrade Villanueva, Sergio Lupo, Sandra Wagner Cardoso, Evy Yunihastuti, Yanri Wijayanti Subronto, Munawaroh Fitriah, Sudirman Katu, Dannae Brown, Emmanuelle Papot, Jolie Hutchinson, Anthony Kelleher, Josh Hanson, Nila J Dharan, Kathy Petoumenos, Gail V Matthews, the D2EFT Study Team, Marcelo Losso, Sergio Lupo, Ana Melisa Solari, Silvina Tavella, David Cooper, Sean Emery, Mark Polizzotto, Anthony Kelleher, Matthew Law, Gail V Matthews, Beatriz Grinsztejn, Marcelo Wolff, Otto Sussmann, Mohamed Cisse, Poongulali Selvamuthu, Usman Hadi, Sudirman Katu, Yanri Wijayanti Subronto, Evy Yunihastuti, Iskandar Azwa, Ting Soo, Sounkalo Dao, Juan Luis Mosqueda Gómez, Juan Sierra Madero, Jaime F Andrade Villanueva, Nnakelu Eriobu, Jaclyn Ann, Richard Kaplan, Lerato Mohapi, Anchalee Avihingsanon, Ploenchan, Suwimon Khusuwan, Weerawat Manosuthi, Margaret Borok

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,763

Funders: World Health Organization, ViiV Healthcare, National Institutes of Health, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases, Janssen Pharmaceuticals, Unitaid

Awards: G1825655257, G3122772534, G4365152597

OpenAlex ID: W4411728811