The following is a summary of “D2EFT: DOLUTEGRAVIR AND DARUNAVIR EVALUATION IN ADULTS FAILING FIRST-LINE HIV THERAPY”, presented by Gail Matthews, Margaret Borok, Nnekelu Eriobou, Richard Kaplan, N Kumarasamy, Anchalee Avihingsanon, Marcelo H. Losso, Iskander Shah Azwa, Muhammad Karyana, Sounkalo Dao, Mohamed Cisse, Emmanuelle Papot, Simone Jacoby, Jolie Hutchison, Matthew G. Law

Limited comparative randomised data on the efficacy and safety of second-line antiretroviral (ARV) regimens, after failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) across diverse geographical settings are available. The D2EFT trial was conducted to investigate this, as an international open-label randomised study comparing dolutegravir (DTG) with ritonavir boosted darunavir (DRV/r) versus DTG with fixed tenofovir and lamivudine or emtricitabine (TDF/XTC) versus standard of care (SOC: DRV/r+2NRTIs with a rotation of nucleosides or in adaptation to HIV genotyping) in adult HIV-1 patients whose first-line NNRTI therapy has failed.

The trial was composed of 2 stages: Stage 1 compared DTG+DRV/r to SOC, and Stage 2 added a third arm (DTG+TDF/XTC). The primary outcome was to demonstrate non-inferiority against SOC in terms of HIV-RNA< 50c/mL at 48 weeks, using a delta=12%. About 831 participants from 14 countries across Asia, Africa and Latin America were included in the trial, with a median age of 55 years and 54% being female. The median CD4 was 206 cells/mm3 and median HIV-RNA was 4.2log10c/ml, with an 85% failure of efavirenz-based first-line therapy.

At 48 weeks, the percentage with HIV-RNA< 50c/ml in Stage 1 was 75.4% SOC vs 84.1% DTG+DRV/r; in Stage 2: 71.4% SOC, 84.7% DTG+DRV/r, 78.0% DTG+TDF/ XTC. Compared to the SOC, the % difference in HIV-RNA < 50c/ml was -8.6% (95% CI; -15.5, -1.7, P=0.02) for DTG+DRV/r, and -6.7 (-14.4, 1.2, P=0.09) for DTG+TDF/XTC. Additionally, mean CD4 gain to week 48 was significantly greater in both DTG+DRV/r and DTG+TDF/XTC compared to SOC. 14 deaths (none treatment related) and 97 SAEs (14 possibly treatment related) occurred, as well as 35 pregnancies (24 deliveries) with no congenital defects. The results of the D2EFT trial indicate that, in individuals with failing NNRTI-based first-line ARV, a switch to either DTG+DRV/r or DTG+TDF/XTC, without universal access to genotyping, was non-inferior in achieving viral suppression compared to DRV/r+2NRTIs, with DTG+DRV/r also achieving superiority.