Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial

• Published in: Antiviral therapy Vol. 24; no. 6; pp. 425 - 435
• Main Authors: Gatell, Jose M, Morales-Ramirez, Javier O, Hagins, Debbie P, Thompson, Melanie, Arastéh, Keikawus, Hoffmann, Christian, Raffi, François, Osiyemi, Olayemi, Dretler, Robin, Harvey, Charlotte, Xu, Xia, Plettenberg, Andreas, Smith, Don E, Portilla, Joaquín, Rugina, Sorin, Kumar, Sushma, Frobose, Colleen, Wan, Hong, Rodgers, Anthony, Hwang, Carey, Teppler, Hedy
• Format: Journal Article
• Language: English
• Published: England International Medical Press 01.01.2019
• Subjects: Antiretroviral drugs; Antiretroviral therapy; Central nervous system; Efavirenz; Emtricitabine; HIV; Human immunodeficiency virus; Ribonucleic acid; RNA; Safety; Tenofovir
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP3323

The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). A Phase IIb double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100,000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 24 (Parts I+II combined). 210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002). Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.