Antiretroviral Activity, Pharmacokinetics, and Safety of MK-8527, an Oral Nucleoside Reverse Transcriptase Translocation Inhibitor, in Adults With HIV-1 Who Had Not Previously Taken Antiretroviral Agents: Results From 2 Open-Label, Phase 1 Studies.

BACKGROUND

MK-8527 is a novel oral nucleoside reverse transcriptase translocation inhibitor under clinical development as HIV-1 (HIV) prevention. Two Phase 1 single-dose monotherapy studies were conducted to evaluate antiretroviral activity, pharmacokinetics (PK), and safety of MK-8527 in adults with HIV who had not previously taken antiretroviral agents.

METHODS

In 2 Phase 1 studies, participants received a single oral dose of MK-8527 (0.25, 0.5, 1, 3, or 10 mg). Reduction in viral load (measured as log10 plasma HIV RNA copies/mL at 7 days post-dose), PK of plasma MK-8527 through 7 days, intracellular MK-8527-triphosphate (TP, the active form of MK-8527) through 28 days, exposure-response relationship, and safety through 28 days were assessed. Adverse events were descriptively summarized.

RESULTS

In total, 37 participants completed the studies. After single doses of MK-8527 0.5 to 10 mg, the mean decrease in HIV RNA at 7 days-post dose was ≥1.0 log10 copies/mL. The inhibitory quotient (defined as the ratio of MK-8527-TP concentration at 168 hours post-dose [C168] to the mean intracellular concentration of MK-8527-TP at the half-maximal inhibitory concentration [IC50]) exceeded 3 at single doses of ≥0.5 mg. MK-8527 at all dose levels was well tolerated, with a limited number of mild or moderate adverse events that were determined by investigators to be unrelated to the study treatment.

CONCLUSIONS

In adults with HIV who had not previously taken antiretroviral agents, single doses of MK-8527 as low as 0.5 mg achieved ≥1.0 log10 decreases in HIV RNA at 7 days post-dose administration.

CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov NCT03615183, NCT05494736.