Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor (NNRTI) with demonstrated efficacy in treatment-naïve adults with HIV-1.
In this open-label, active-controlled, non-inferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or an NNRTI were randomized (2:1) to switch to once-daily, single-tablet doravirine 100mg with lamivudine 300mg and tenofovir disoproxil fumarate 300mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24, and a secondary comparison between the groups at week 24 (non-inferiority margin, -8%).
670 participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL (difference -0.9 [-4.7, 3.0]). At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating non-inferiority vs Baseline Regimen at week 24 (difference -3.8 [-7.9, 0.3]). In participants on ritonavir-boosted PI at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (p<0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively.
Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy.
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1Royal Free Hospital, Department of HIV Medicine, London UK
2Medstar Georgetown University Hospital, Div. of Infectious Diseases and Travel Medicine, Washington DC, USA
3University of Paris Diderot, Hôpital Saint-Louis, Paris, France
4ASST Fatebenefratelli Sacco Hospital, Department of Infectious Diseases, Milan, Italy
5Fundación Huésped and Buenos Aires University, Buenos Aires, Argentina
6Infektiologikum, Centre for Infectious Diseases, Frankfurt, Germany
7HIV Unit, Infectious Diseases Service, Hospital Clinic, Barcelona, Spain
8Merck & Co., Inc., Kenilworth, NJ USA.
Corresponding Author: Wayne Greaves, MD, Merck Sharp & Dohme Corp., 126 E. Lincoln Avenue, RY34-A484, Rahway, NJ 07065-0900, (732) 594-3736, 305-7403, email@example.com
Conflicts of Interest and Source of Funding: Funding for this research was provided by Merck Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MJ has received grants and consulting fees from Gilead and Viiv. PK is on Advisory Boards for ViiV, Janssen, Merck, and Theratechnologies; has received grants from Merck, ViiV, Gilead, and Theratechnologies; and owns stock in Johnson & Johnson, Gilead, Merck, Pfizer, and GSK. J-MM has received grants from Gilead and consulting fees (Advisory Board) from Gilead and MSD. GR has received Advisory board and speaker fees from JanssenCilag, Abbvie, Gilead Science, ViiV, MSD, and Angelini. PC is an Advisory Board member for MSD and ViiV and has received research grants from AbbVie, MSD, and ViiV. MB has no conflicts to declare. JM has received honoraria, speakers’ fees, consultant fees or funds for research from MSD, Roche, Boehringer-Ingelheim, ViiV, Gilead, Janssen, BMS, and Abbvie. YZ, CM, SK, PS, GJH, CH, and WG are current or former employees of MSD.
Parts of the data were presented at: IDWeek 2018, San Francisco CA, 04-Oct-2018.