Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial

This study is registered with ClinicalTrials.gov, NCT02217904, and EudraCT, 2014-002192-28.FindingsBetween Sept 17, 2015, and May 11, 2017, we enrolled 30 participants (six per panel). Islatravir was generally well tolerated. 27 (90%) participants had 60 adverse events after receipt of drug, of which 21 (35%) were deemed to be drug related. The most common (n>1) drug-related adverse events were headache (in nine [30%] participants) and diarrhoea (in two [7%]). No serious adverse events were reported, and no participants discontinued due to an adverse event. Plasma islatravir pharmacokinetics and intracellular islatravir-triphosphate pharmacokinetics were approximately dose proportional. The islatravir-triphosphate intracellular half-life was 78·5–128·0 h. Least-squares mean HIV-1 RNA at 7 days after dose decreased from 1·67 log10 copies per mL (95% CI 1·42–1·92) at 10 mg dose to 1·20 log10 copies per mL (0·95–1·46) at 0·5 mg dose. No genetic changes consistent with development of viral resistance were detected.InterpretationSingle doses of islatravir as low as 0·5 mg significantly suppressed HIV-1 RNA by more than 1·0 log at day 7 in treatment-naive adults with HIV-1 infection and were generally well tolerated, supporting the further development of islatravir as a flexible-dose treatment for individuals with HIV-1 infection.FundingMerck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc, Kenilworth, NJ, USA.
Source: The Lancet HIV - Category: Infectious Diseases Source Type: research