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.

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.

• Authors: Jose M Gatell, Javier O Morales-Ramirez, Debbie P Hagins, Melanie Thompson, Keikawus Arastéh, Christian Hoffmann, François Raffi, Olayemi Osiyemi, Robin Dretler, Charlotte Harvey, Xia Xu, Andreas Plettenberg, Don E Smith, Joaquín Portilla, Sorin Rugina, Sushma Kumar, Colleen Frobose, Hong Wan, Anthony Rodgers, Carey Hwang, Hedy Teppler
• Journal: Antiviral therapy (Antivir Ther) Vol. 24 Issue 6 Pg. 425-435 ( 2019) ISSN: 2040-2058 [Electronic] England
• PMID: 31355775 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-HIV Agents
• Benzoxazines
• Cyclopropanes
• Pyridones
• Triazoles
• doravirine
• efavirenz

Topics

• Adult
• Aged
• Alkynes
• Anti-HIV Agents (administration & dosage, adverse effects)
• Antiretroviral Therapy, Highly Active
• Benzoxazines (administration & dosage, adverse effects)
• Cyclopropanes
• Female
• HIV Infections (drug therapy, virology)
• HIV-1 (drug effects, genetics)
• Humans
• Male
• Middle Aged
• Pyridones (administration & dosage, adverse effects)
• Treatment Outcome
• Triazoles (administration & dosage, adverse effects)
• Viral Load
• Young Adult