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Islatravir safety analysis through week 96 from a phase 2 trial in treatment naïve adults with HIV-1 infection

Title
Islatravir safety analysis through week 96 from a phase 2 trial in treatment naïve adults with HIV-1 infection
Presenter
Douglas Cunningham
Authors
D. Cunningham * (1), J.-M. Molina (2), Y. Yazdanpanah (3), A.A. Saud (4), C.C. Anania (5), S.O. Klopfer (6), A. Grandhi (6), K. Eves (6), D. Hepler (6), C. Hwang (6), R. Lahoulou (7), T.A. Correll (6)
Institutions
(1) Pueblo Family Physicians Ltd, Phoenix, United States, (2) Saint-Louis Hospital and University of Paris, Department of Infectious Disease, Paris, France, (3) Bichat Hospital, Paris, France, (4) University of Chile, Santiago, Chile, (5) Hospital Hernan Henriquez Aravena of Temuco, Temuco, Chile, (6) Merck & Co., Inc., Kenilworth, United States, (7) MSD France, Puteaux, France

BACKGROUND: Islatravir (ISL, MK-8591) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for treatment and prevention of HIV-1 infection. We previously showed that ISL + doravirine (DOR) was effective in maintaining viral suppression through week 96 and was well-tolerated. Here we present a detailed safety analysis of those results.
METHODS: In this Phase 2b trial, treatment-naïve adults with HIV-1 were randomized to receive ISL (0.25, 0.75, or 2.25mg) + DOR (100mg) and lamivudine (3TC, 300mg) QD, or a fixed-dose combination of DOR (100mg), 3TC (300mg), and tenofovir disoproxil fumarate (300mg) (DOR/3TC/TDF) QD. In the ISL groups, participants who achieved HIV-1 RNA <50 copies/mL at Week 20 or later, stopped 3TC at the next study visit. All participants receiving ISL were switched to ISL (0.75mg) between weeks 60 and 84. For the current analysis, we conducted a detailed review of adverse events (AEs) and examined these AEs for study periods at weeks 0-48, 48-96 and 0-96.
RESULTS: 121 participants received drug and were included in the analyses. Similar AE rates between treatment arms were observed across all arms of the trial for each time period. No dose-dependent difference in the safety profile of ISL was observed. AEs were more frequent in the first 48 weeks of the trial, as compared to the second 48-week period, for all treatment arms (see table). During the 96 week-period overall, diarrhea, mostly mild and transient, was more frequently reported for DOR/3TC/TDF (19.4%) as compared to ISL groups (combined 7.9%), while headache was more common in ISL groups (combined 11.1%) as compared to the DOR/3TC/TDF group (6.5%).
CONCLUSIONS: ISL was well-tolerated, regardless of dose, through 96 weeks of treatment, with most AEs reported as mild and transient. No participants had drug-related AEs or discontinued the study due to a drug-related AE between weeks 48-96.