Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results.

Background: Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor approved for 200 mg twice-daily dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing. Methods: In this single-arm, open-label study, 79 treatment- naive HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily to assess antiviral activity, safety and tolerability. ARV activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA<50 copies/ml (intention-to-treat, missing = failure). Results: Of 79 eligible subjects, 90% were men, 62% African- American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log(10) copies/ml (4.07, 5.04). A total of 69 (87%) completed a week 48 visit and 61 (77%, 95% CI 66%, 86%) achieved HIV-1 RNA<50 copies/ml at week 48. At time of virological failure, genotypic resistance-associated mutations were detected in three participants, two with E138K (one alone and one with additional mutations). Median (95% CI) CD4(+) cell count increase was 163 (136, 203) cells/mu l. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality >= Grade 3 and three participants (3.8%) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths. Conclusions: In this study of ARV-naive HIV-positive adults, once-daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once-daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naive individuals.