Forty-eight-week efficacy and safety and early CNS tolerability of doravirine (MK-1439), a novel NNRTI, with TDF/FTC in ART-naive HIV-positive patients.
BACKGROUND
Doravirine (DOR) is an investigational NNRTI (aka MK-1439) that retains activity against common NNRTI-resistant mutants. We have previously reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb study in ART-naïve HIV-1-positive patients (1). At doses of 25, 50, 100 and 200 mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2.


METHODS
Patients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8) CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre-specified CNS events (all causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined).


RESULTS
Part 1 week 48 efficacy and safety results are shown below.


CONCLUSIONS
In ART-naïve, HIV-1-positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and immunological effect at week 48 and was generally safe and well tolerated. Patients who received DOR 100 mg qd had significantly fewer treatment-emergent CNS AEs by week 8 than those who received EFV.
Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain.
Josep M
JM
Gatell
Clinical Research, Clinical Research Puerto Rico, San Juan, Puerto Rico.
Javier O
JO
Morales-Ramirez
Country Health Department, Chatham Country Health, Savannah, USA.
Debbie P
DP
Hagins
AIDS Research Consortium of Atlanta, Atlanta, USA.
Melanie
M
Thompson
EPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.
Arasteh
A
Keikawus
ICH Study Center, Hamburg, Germany.
Christian
C
Hoffmann
Spitalul Clinic de Boli Infectioase, Costanta, Romania.
Sorin
S
Rugina
Triple O Research Institute PA, West Palm Beach, USA.
Olayemi
O
Osiyemi
Spitalul Clinic de Boli Infectioase, Costanta, Romania.
Simona
S
Escoriu
Infectious Disease Specialists of Atlanta, Decatur, USA.
Robin
R
Dretler
Merck & Co. Inc, Whitehouse Station, New Jersey, USA.
Charlotte
C
Harvey
Merck & Co. Inc, Whitehouse Station, New Jersey, USA.
Xia
X
Xu
Merck & Co. Inc, Whitehouse Station, New Jersey, USA.
Hedy
H
Teppler