Abstract Body

In the phase 3 DRIVE-AHEAD trial, a once-daily single-tablet regimen of doravirine 100 mg, lamivudine 300 mg, and tenofovir DF 300 mg (DOR/3TC/TDF) demonstrated non-inferior efficacy and a superior safety profile for neuropsychiatric events and fasting lipids compared to efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg (EFV/FTC/TDF) at Week 48. To further characterize the effects of DOR/3TC/TDF, Week 48 results were examined by pre-specified subgroups (efficacy) and selected prognostic subgroups (safety).

DRIVE-AHEAD is a randomized (1:1), multicenter, double-blind, 96-week non-inferiority trial of DOR/3TC/TDF vs EFV/FTC/TDF in HIV-1 infected treatment-naïve adults. Randomization was stratified by screening HIV-1 RNA (≤/>100,000 copies/mL) and hepatitis B/C co-infection (yes/no). The primary endpoint was the proportion of participants achieving HIV-1 RNA <50 copies/mL at Week 48 (FDA Snapshot approach). For the current analysis, Week 48 efficacy results were summarized within pre-specified subgroups using the Observed Failure approach (participants with data missing for reasons other than lack of efficacy were excluded). Adverse events were also summarized by selected subgroups (gender, race/ethnicity, hepatitis co-infection, and baseline CD4+ T-cell count).

Baseline characteristics were balanced across the treatment groups. In the primary analysis, HIV-1 RNA <50 copies/mL was achieved by 84% of DOR/3TC/TDF recipients and 81% of EFV/FTC/TDF recipients at Week 48 (difference 3.5%, 95% CI [-2.0, 9.0]). Of the 728 participants who received study drug (364 in each treatment group), 677 (93%) were included in the subgroup efficacy analyses. Across the prespecified and selected demographic and baseline prognostic factors, the proportions of participants with HIV-1 RNA <50 copies/mL at Week 48 were comparable between the treatment regimens (table). Similar results were observed using the HIV-1 RNA cutoffs of 40 and 200 copies/mL and in the change from baseline in CD4+ T-cell counts. In the safety analysis, similar adverse event rates between treatment groups were observed across the subgroups.

At Week 48, across all baseline subgroups and prognostic factors, DOR/3TC/TDF demonstrated virologic and immunologic efficacy and safety comparable to that of EFV/FTC/TDF in HIV-1 treatment-naïve adults.