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. 2025 Jun 27:ciaf346.
doi: 10.1093/cid/ciaf346. Online ahead of print.

A randomised 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

Phyo Pyae Nyein  1 , Margaret Borok  2 , Nnakelu Eriobu  3 , Richard Kaplan  4 , Nagalingeswaran Kumarasamy  5 , Anchalee Avihingsanon  6 , Marcelo H Losso  7 , Iskandar Azwa  8 , Muhammad Karyana  9 , Sounkalo Dao  10 , Mohamed Cisse  11 , Jaime F Andrade Villanueva  12 , Sergio Lupo  13 , Sandra Wagner Cardoso  14 , Evy Yunihastuti  15 , Yanri Wijayanti Subronto  16 , Munawaroh Fitriah  17 , Sudirman Katu  18 , Dannae Brown  19 , Emmanuelle Papot  1 , Jolie Hutchinson  1 , Anthony Kelleher  1 , Josh Hanson  1 , Nila J Dharan  1 , Kathy Petoumenos  1 , Gail V Matthews  1 ; DEFT Study Team
Collaborators, Affiliations

A randomised 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

Phyo Pyae Nyein et al. Clin Infect Dis. .

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 HIV who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to one of ritonavir-boosted darunavir plus two 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% 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.

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