Analysis of protocol defined virologic failure through week 48 from a phase 2 trial (P011) of islatravir and doravirine in treatment-naïve adults with HIV-1 infection
BACKGROUND: Islatravir (ISL,MK-8591) is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for treatment and prevention of HIV-1 infection. The objective of this analysis is to show detailed data of participants who discontinued with protocol-defined virologic failure (PDVF) from the phase-2 trial of islatravir (ISL) and doravirine (DOR).
METHODS: Randomized, double-blind, dose-ranging trial participants initially
received ISL(0.25, 0.75, or 2.25 mg) with DOR(100 mg) and lamivudine(3TC,
300 mg) or fixed-dose combination of DOR, 3TC, and tenofovir disoproxil
fumarate(DOR/3TC/TDF) daily. Participants receiving ISL achieving HIV-1
RNA<50 copies/mL at week-20 or later stopped 3TC at next visit. PDVF was
conservatively defined as rebound with confirmed HIV-1 RNAâ?¥50 copies/mL after
suppression any time during the trial or non-response with failure to achieve
HIV-1 RNA<50 copies/mL by week-48. Participants with PDVF were required to discontinue
from the trial.
RESULTS: 121 participants received study drug and were included in
analyses. At week-48, 89.7% (26/29), 90.0% (27/30), 77.4% (24/31) of randomized
participants achieved HIV-1 RNA<50 copies/mL in the 0.25, 0.75, and 2.25mg
ISL groups, respectively, compared to 83.9%(26/31) with DOR/3TC/TDF. Six
participants had PDVF; 2 rebounders each in the 0.25 and 0.75 mg ISL groups, 1
non-responder in the 2.25mg ISL group and 1 rebounder in the DOR/3TC/TDF group.
All confirmatory HIV-1 RNA Levels were <80copies/mL (Figure1); none met
criteria for resistance testing. Despite changing to new regimens, three of six
participants (1 each from the 0.25 and 0.75 mg ISL groups and 1 from the
DOR/3TC/TDF group) continued to have low-level viremia during 42-day
post-discontinuation assessment.
CONCLUSIONS: Rates of PDVF were low and all participants who discontinued due to PDVF had HIV-1 RNA levels below the clinically significant level of 200 copies/mL. The observed low-level viremia was comparable to levels detected in other treatment-naïve studies.
Figure 1: HIV-1 RNA levels Over Time for Participants with PDVF
C. Orkin * (1), J.-M. Molina (2), Y. Yazdanpanah (3), C. Chahlin Anania (4), E. DeJesus (5), J. Eron (6), S. Klopfer (7), A. Grandhi (7), K. Eves (7), D. Rudd (7), M. Robertson (7), P. Sklar (7), C. Hwang (7), G. Hanna (7), T. Correll (7)
(1) Queen Mary Univeristy of London, London, United Kingdom, (2) St. Louis Hospital and University, Paris, France, (3) Bichat Hospital, Paris, France, (4) Hospital Hernan Henriaquez Aravena of Temuco, Temuco, Chile, (5) Orlando Immunology Center, Orlando, United States, (6) University of North Carolina, Chapel Hill, United States, (7) Merck & Co., Inc., Kenilworth, United States