Antiretroviral Activity and Safety of Once-Daily Etravirine in Treatment-Naive HIV-Infected Adults: 48-Week Results

• Published in: Antiviral therapy Vol. 21; no. 1; pp. 55 - 64
• Main Authors: Floris-Moore, Michelle A, Mollan, Katie, Wilkin, Aimee M, Johnson, Marc A, Kashuba, Angela DM, Wohl, David A, Patterson, Kristine B, Francis, Owen, Kronk, Catherine, Eron, Joseph J
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2016
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Biomarkers; CD4 Lymphocyte Count; Drug Resistance, Viral; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1; Humans; Lentivirus; Male; Pyridazines - administration & dosage; Pyridazines - adverse effects; Pyridazines - therapeutic use; Retroviridae; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - therapeutic use; Time Factors; Treatment Failure; Treatment Outcome; Viral Load; Young Adult
• ISSN: 1359-6535; 2040-2058; 2040-2058
• DOI: 10.3851/IMP2982

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 log10 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/μl. 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. ClinicalTrials.gov NCT00959894.