Jose M Gatell1,2, Javier O Morales-Ramirez3, Debbie P Hagins4, Melanie Thompson5, Keikawus Arastéh6, Christian Hoffmann7, François Raffi8, Olayemi Osiyemi9, Robin Dretler10, Charlotte Harvey11, Xia Xu11, Andreas Plettenberg12, Don E Smith13, Joaquín Portilla14, Sorin Rugina15, Sushma Kumar11, Colleen Frobose11, Hong Wan11, Anthony Rodgers11, Carey Hwang11, Hedy Teppler11. 1. Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain. 2. Present address: ViiV Healthcare, Barcelona, Spain. 3. Clinical Research Puerto Rico, San Juan, Puerto Rico. 4. Chatham County Health Department, Savannah, GA, USA. 5. AIDS Research Consortium of Atlanta, Atlanta, GA, USA. 6. EPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany. 7. ICH Study Center, Hamburg, Germany. 8. Infectious Diseases Department and INSERM CIC 1413, University Hospital of Nantes, Nantes, France. 9. Triple O Research Institute PA, West Palm Beach, FL, USA. 10. Infectious Disease Specialists of Atlanta, Decatur, GA, USA. 11. Merck & Co., Inc., Kenilworth, NJ, USA. 12. ifi-Institute for Infections, Hamburg, Germany. 13. Albion Centre, Sydney, Australia. 14. Hospital General Universitario de Alicante/ISABIAL, Alicante, Spain. 15. Ovidius University, Clinical Infectious Diseases Hospital, Constanta, Romania.
Abstract
BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: 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). RESULTS: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). CONCLUSIONS:Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.
RCT Entities:
BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: 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). RESULTS: 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). CONCLUSIONS:Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.
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