LB2. Switch to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial
Session: Oral Abstract Session: Late Breaker Oral Abstracts: HIV and Antibiotic Trials
Thursday, October 4, 2018: 10:40 AM
Room: S 151-153

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.

Princy Kumar, M.D.1, Margaret Johnson, MD, FRCP2, Jean-Michel Molina, MD3, Giuliano Rizzardini, MD4, Pedro Cahn, MD, PhD5, Markus Bickel, MD6, Josep Mallolas, MD7, Yan Zhou, PhD8, Cristiana Morais, PhD8, Sushma Kumar, PhD8, Peter Sklar, MD, MPH8, George J. Hanna, MD8, Carey Hwang, MD, PhD8 and Wayne Greaves, MD8, (1)Division of Infectious Diseases and Travel Medicine, Medstar Georgetown University Hospital, Washington, DC, (2)Royal Free Hospital, London, United Kingdom, (3)University of Paris Diderot and Hôpital Saint-Louis, Paris, France, (4)ASST Fatebenefratelli Sacco, Milan, Italy, (5)Fundación Huésped, Buenos Aires, Argentina, (6)Infektiologikum, Frankfurt, Germany, (7)University of Barcelona, Barcelona, Spain, (8)Merck & Co., Inc., Kenilworth, NJ

Disclosures:

P. Kumar, Merck, Pfizer, Janssen,: Grant Investigator and Shareholder , Research grant . GSK, Gilead, Teratechnologies, TaiMed,: Grant Investigator , Scientific Advisor and Shareholder , Consulting fee and Research grant .

M. Johnson, None

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 .

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.