Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.

Abstract

Background:

Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile.

Methods:

DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment-naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%).

Results:

Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs +13.3 mg/dL, respectively).

Conclusions:

In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF.

Clinical Trials Registration:

NCT02403674.

• Authors: Chloe Orkin, Kathleen E Squires, Jean-Michel Molina, Paul E Sax, Wing-Wai Wong, Otto Sussmann, Richard Kaplan, Lisa Lupinacci, Anthony Rodgers, Xia Xu, Gina Lin, Sushma Kumar, Peter Sklar, Bach-Yen Nguyen, George J Hanna, Carey Hwang, Elizabeth A Martin, DRIVE-AHEAD Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 68 Issue 4 Pg. 535-544 (02 01 2019) ISSN: 1537-6591 [Electronic] United States
• PMID: 30184165 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• RNA, Viral
• Reverse Transcriptase Inhibitors

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-HIV Agents (administration & dosage)
• Antiretroviral Therapy, Highly Active (methods)
• Double-Blind Method
• Female
• HIV Infections (drug therapy, virology)
• HIV-1 (isolation & purification)
• Humans
• Male
• Middle Aged
• RNA, Viral (blood)
• Reverse Transcriptase Inhibitors (administration & dosage)
• Treatment Outcome
• Viral Load
• Young Adult