Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using...

Area of Science:

• Pharmacokinetics and Drug Delivery
• HIV Prevention and Treatment
• Biomedical Engineering

Background:

• Long-acting antiretrovirals (ARVs) are crucial for improving HIV treatment adherence.
• Islatravir (ISL) shows promise for long-acting HIV prevention and treatment.
• Microneedle array patches (MAPs) offer a pain-free, transdermal delivery method for extended drug release.

Purpose of the Study:

• To predict the pharmacokinetics of ISL delivered via MAP using physiologically based pharmacokinetic (PBPK) modeling.
• To identify key MAP characteristics for sustaining effective ISL concentrations over extended intervals.
• To assess the potential of ISL-MAPs for long-term HIV management.

Main Methods:

• Developed and verified an ISL PBPK model against oral administration data.
• Integrated an intradermal PBPK model to simulate MAP administration.
• Simulated various nanoparticle release rates and MAP bioavailability scenarios.

Main Results:

• The ISL PBPK model accurately predicted drug disposition.
• ISL MAP doses (15-80 mg) could maintain target ISL-TP concentrations for 3, 6, or 12 months.
• Nanoparticle release rate and MAP bioavailability significantly impacted dosing strategy effectiveness.

Conclusions:

• PBPK modeling successfully predicted ISL pharmacokinetics for oral and MAP administration.
• Optimal MAP doses and release rates were identified for sustained ISL-TP concentrations up to 12 months.
• ISL is a viable candidate for MAP-based long-acting HIV prevention and treatment.