{"doi":"10.1093/cid/ciaf346","title":"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","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.","journal":"Clinical Infectious Diseases","year":2025,"id":534001,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9448,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769462,"name":"Margaret Borok","orcid":"0000-0002-1234-0913","position":1,"is_corresponding":false},{"id":950988,"name":"Nnakelu Eriobu","orcid":"0000-0003-2528-8082","position":2,"is_corresponding":false},{"id":950989,"name":"Richard Kaplan","orcid":"0000-0003-1565-4704","position":3,"is_corresponding":false},{"id":380562,"name":"Nagalingeswaran Kumarasamy","orcid":"0009-0006-2252-5731","position":4,"is_corresponding":false},{"id":424033,"name":"Anchalee Avihingsanon","orcid":"0000-0003-3222-9611","position":5,"is_corresponding":false},{"id":12017,"name":"Marcelo Losso","orcid":"0000-0002-4273-4833","position":6,"is_corresponding":false},{"id":376621,"name":"Iskandar Azwa","orcid":"0000-0003-1977-6709","position":7,"is_corresponding":false},{"id":321455,"name":"Muhammad Karyana","orcid":"0000-0002-7785-5731","position":8,"is_corresponding":false},{"id":950987,"name":"Sounkalo Dao","orcid":"0000-0002-9628-8728","position":9,"is_corresponding":false},{"id":950986,"name":"Mohamed Cissé","orcid":"0000-0002-6859-8745","position":10,"is_corresponding":false},{"id":373715,"name":"Jaime Andrade‐Villanueva","orcid":"0000-0003-1948-655X","position":11,"is_corresponding":false},{"id":535828,"name":"Sergio Lupo","orcid":null,"position":12,"is_corresponding":false},{"id":531919,"name":"Sandra Wagner Cardoso","orcid":"0000-0001-5230-0003","position":13,"is_corresponding":false},{"id":376622,"name":"Evy Yunihastuti","orcid":"0000-0001-6650-0559","position":14,"is_corresponding":false},{"id":1213183,"name":"Yanri Wijayanti Subronto","orcid":"0000-0002-6367-4884","position":15,"is_corresponding":false},{"id":1394090,"name":"Munawaroh Fitriah","orcid":"0000-0002-7617-9874","position":16,"is_corresponding":false},{"id":1213951,"name":"Sudirman Katu","orcid":null,"position":17,"is_corresponding":false},{"id":951478,"name":"Dannae Brown","orcid":null,"position":18,"is_corresponding":false},{"id":950984,"name":"Emmanuelle Papot","orcid":"0000-0003-2782-0263","position":19,"is_corresponding":false},{"id":364604,"name":"Jolie Hutchinson","orcid":"0000-0003-1936-3808","position":20,"is_corresponding":false},{"id":535018,"name":"Anthony D. 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