Dolutegravir and Darunavir Evaluation in Adults Failing Therapy
Summary
D²EFT is a randomised, open-label study in HIV-1 infected patients failing first-line antiretroviral therapy (ART). The study compares 2 regimens of second-line ART (dolutegravir and darunavir pharmaco-enhanced with ritonavir and dolutegravir and 2 prespecified NRTIs) with the WHO recommended regimen of 2NRTIs plus a ritonavir-boosted PI (Standard of Care (SOC)). 1,010 participants from 14 predominantly low-middle income countries will be followed for 96 weeks with the primary endpoint at week 48. The design is based on the hypothesis that one or both of the new regimens will be non-inferior to SOC in terms of virologic control while being easier to take, economically viable and affording simplification of treatment programs.
Timeline
- Start
- 2017-11-23
- Primary completion
- 2022-11-11
- Completion
- 2023-10-31
Outcome
Met primary endpoint
paper the difference in virological suppression was 8·6% (95% CI 1·7 to 15·5; p=0·016) for dolutegravir plus ritonavir-boosted darunavir PMID 38788744 ↗
paper was non-inferior in achieving viral suppression compared with ritonavir-boosted darunavir plus two NRTIs. PMID 38788744 ↗
Publications
- Nyein PP, Donoghoe MW, Eriobu N, Uche B, Kaplan R, Carey D, Brown D, Kundro M, Dharan NJ, Hanson J, Petoumenos K, Matthews GV; the D EFT study group. Cardiometabolic impact of dolutegravir as second-line therapy: secondary analysis of a randomized controlled trial. AIDS. 2026 Jul 1;40(7):937-948. doi: 10.1097/QAD.0000000000004476. Epub 2026 Mar 2.
- D2EFT Study Group. Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial. Lancet HIV. 2024 Jul;11(7):e436-e448. doi: 10.1016/S2352-3018(24)00089-4. Epub 2024 May 21.
- Nyein PP, Petoumenos K, Borok M, Eriobu N, Kumarasamy N, Avihingsanon A, Azwa I, Dao S, Cisse M, Dharan NJ, Hanson J, Matthews GV. Associations Between Antiretroviral Regimen and Changes in Blood Pressure: Results From the D2EFT Study. Clin Infect Dis. 2025 Feb 5;80(1):160-163. doi: 10.1093/cid/ciae256.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Darunavir | Small molecule | 800 mg | Oral |
| Subject | Dolutegravir | Other / unclassified | 50 mg | Oral |
| Subject | Lamivudine | Other / unclassified | 300 mg | — |
| Subject | Tenofovir disoproxil fumarate | Small molecule | 300 mg | — |
| Subject | emtricitabine | Other / unclassified | 200 mg | — |
| Background | Ritonavir | Other / unclassified | 100 mg | Oral |