Background: Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated efficacy in two Phase 3 trials in treatment-naïve adults with HIV-1.
Methods: This open-label, active-controlled, non-inferiority (NI) trial evaluated a once-daily single-tablet regimen of doravirine 100mg, lamivudine 300mg, and tenofovir disoproxil fumarate 300mg (DOR/3TC/TDF) vs continuation of current therapy in adults with HIV-1 virologically suppressed for ≥6 months on a stable regimen of 2 NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or NNRTI. Participants with screening HIV-1 RNA <40 copies/mL, no history of virologic failure on any regimen, and no resistance to DOR/3TC/TDF were randomized (2:1) to start DOR/3TC/TDF on Day 1 (immediate switch group, ISG) or after 24 weeks (delayed switch group, DSG). The primary endpoint was the proportion (%) of participants with HIV-1 RNA <50 copies/mL (FDA snapshot approach), with the primary comparison between ISG at Week 48 and DSG at Week 24 and a secondary comparison between the groups at Week 24; the NI margin was -8%. The % of participants with HIV-1 RNA ≥50 copies/mL was also analyzed (FDA snapshot approach; NI margin 4%).
Results: 670 participants (447 ISG, 223 DSG) were treated and included in the analyses; 84.5% were male, 76.4% were white, and mean age was 43.3 years. At Week 24, 93.7% (419/447) of ISG vs 94.6% (211/223) of DSG had HIV-1 RNA <50 copies/mL (difference -0.9% [-4.7, 3.0]), and 1.8% of each group had HIV-1 RNA ≥50 copies/mL. At Week 48, 90.8% (406/447) of ISG maintained HIV-1 RNA <50 copies/mL (vs 94.6% of DSG at Week 24; difference -3.8%, 95% CI [-7.9%, 0.3%]), and 1.6% of ISG had HIV-1 RNA ≥50 copies/mL. In the ritonavir-boosted PI stratum, mean changes in fasting LDL-C and non-HDL-C at Week 24 were significantly lower (p<0.0001) in ISG vs DSG (table). Rates of any AE and of drug-related AEs at Week 24 were higher in ISG vs DSG. AEs were mild in most ISG participants (64% of those with any AE; 80% of those with drug-related AEs).
Conclusion: A once-daily single-tablet regimen of DOR/3TC/TDF demonstrated non-inferior efficacy and acceptable safety compared to continuing therapy, and is an option for maintaining viral suppression in patients considering a change in therapy.
Merck, Pfizer, Janssen,:
GSK, Gilead, Teratechnologies, TaiMed,:
J. M. Molina, Merck GIlead ViiV Janssen Teva: Ad Board and Speaker's Bureau , Consulting fee . Gilead Sciences: Grant Investigator , Research support .
G. Rizzardini, ViiV, Gilead Science, MSD, Angelini, and Abbvie: Board Member and Speaker's Bureau , Speaker honorarium . Gliead, ViiV, and MSD: Research Contractor , Research grant .
P. Cahn, Abbvie: Grant , Research grant . Merck: Grant , Advisory Board . ViiV Healthcare: Grant , Advisory Board .
M. Bickel, Merck & Co., Inc.: Research Contractor , Research grant .
J. Mallolas, None
Y. Zhou, Merck & Co., Inc.,: Employee , Salary .
C. Morais, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder , May hold stock/stock options in the company and Salary .
S. Kumar, Merck & Co., Inc.,: Employee and Shareholder , Salary .
P. Sklar, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.: Employee and Shareholder , Salary .
G. J. Hanna, Merck Sharp & Dohme, a subsidiary of Merck & Co., inc.: Employee and Shareholder , May hold stock/stock options in the company. and Salary .
C. Hwang, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder , Salary .
W. Greaves, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee , May hold stock/stock options within the company .
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