Abstract Body

Doravirine (DOR), an investigational NNRTI with a novel resistance profile, was compared with efavirenz (EFV) in a randomized, double-blind, 2-part study in ART-naïve HIV-infected patients also receiving tenofovir/emtricitabine (TDF/FTC). Part 1 evaluated DOR 25, 50, 100, and 200 mg once daily and EFV 600 mg once daily; based on week 24 results, DOR 100 mg once daily was selected for ongoing evaluation. Part 2 enrolled additional patients to receive DOR 100 mg or EFV. At week 24 (Parts 1+2 combined), DOR 100 mg demonstrated antiretroviral activity and immunological effect similar to EFV (each with TDF/FTC) with significantly fewer CNS adverse events. Data through week 48 are now available from this ongoing study.

Week 48 data from patients who received DOR 100 mg or EFV in Part 1 (n=42 per group) and Part 2 (n=66 per group) were combined for this analysis. Patients were stratified at randomization by screening HIV RNA ≤ or >100,000 copies/mL. The primary efficacy endpoint is the proportion of patients with HIV RNA <40 copies/mL, using the non-completer=failure approach.

216 patients (93% male, 80% white, mean age 36 years) were randomized and treated. Mean baseline HIV RNA was 4.6 log10 copies/mL in both the DOR and EFV groups, and mean CD4 counts were 432 and 448 cells/mm3, respectively. 88% of the DOR group and 85% of the EFV group completed 48 weeks of treatment. Reasons for discontinuation included adverse event (n=3 on DOR, 6 on EFV), lack of efficacy (0, 1), and other reasons (10, 9). Efficacy and safety results are shown in the table below. Drug-related AEs with incidence >5% in either treatment group were diarrhea (DOR 0.9%, EFV 6.5%), nausea (7.4%, 5.6%), dizziness (6.5%, 25.9%), headache (2.8%, 5.6%), abnormal dreams (5.6%, 14.8%), insomnia (6.5%, 2.8%), nightmares (5.6%, 8.3%), and sleep disorder (4.6%, 6.5%). There were no discontinuations due to drug-related AEs after week 24. Laboratory abnormalities ≥Grade 2 were uncommon in both groups.

DOR 100 mg once daily demonstrated antiretroviral activity and immunological effect similar to EFV (each with TDF/FTC) and was generally safe and well tolerated during 48 weeks of treatment in ART-naïve, HIV-1 infected patients. Drug-related AEs were significantly less frequent in the DOR group compared with the EFV group.