A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for...

Area of Science:

• Pharmacology
• Infectious Diseases
• Drug Delivery Systems

Background:

• Islatravir (MK-8591), a deoxyadenosine analog, is under development for HIV-1 treatment and prevention.
• An islatravir-eluting implant offers a potential new method for HIV-1 pre-exposure prophylaxis (PrEP).

Purpose of the Study:

• To evaluate the safety, tolerability, and pharmacokinetics of a next-generation islatravir-eluting implant for PrEP.
• To determine if islatravir concentrations in plasma and peripheral blood mononuclear cells (PBMCs) remain above the established PrEP threshold.

Main Methods:

• A randomized, double-blind, placebo-controlled phase 1 trial involving 36 participants at low risk of HIV infection.
• Participants received a 12-week subdermal implant containing 48 mg, 52 mg, or 56 mg of islatravir, or a placebo.
• Safety, tolerability, and islatravir/islatravir triphosphate levels in plasma and PBMCs were assessed during and after implant removal.

Main Results:

• The islatravir implants were generally well-tolerated, with no adverse event-related discontinuations.
• No significant dose-dependence was observed in implant-related adverse events.
• Mean islatravir triphosphate levels at day 85 exceeded the 0.05 pmol/10^6 cells PrEP threshold across all dose groups (0.101–0.561 pmol/10^6 cells).

Conclusions:

• Subdermal administration of islatravir via implant is a potentially effective and well-tolerated strategy for HIV-1 PrEP.
• The islatravir-eluting implant demonstrates favorable safety and pharmacokinetic profiles for long-acting PrEP.
• This novel drug delivery system holds promise for improving adherence and accessibility of HIV-1 prevention methods.