PrEPping for the Future

Toward that end, Houston Methodist researchers have developed a long-acting, refillable, subcutaneous implant for sustained release of the HIV drug islatravira—nucleoside reverse transcriptase translocation inhibitor that is in development for HIV PrEP.

In a pre-clinical model, the islatravir-delivering implants provided protective levels of islatravir in all subjects within 24 hours. The levels remained consistent for more than 20 months. When challenged with SHIVSF162P3, the implants conferred 100% protection against infection compared to control groups. SHIVSF162P3 is a CCR5-specific chimeric simian/human immunodeficiency virus that has been shown effective in preclinical assessment of HIV antivirals.

The implants were well-tolerated throughout the study with only mild local tissue inflammation observed and no systemic toxicity. In addition, they found no reduction in total lymphocytes, or CD4+ or CD8+ cells. The impact of PrEP on the global HIV epidemic, including the epidemic closer to home, hinges on effective drugs and delivery platforms. Variable adherence to the current regimens makes it clear that alternative strategies are needed, and the drug-eluting implant has the potential to make a difference. Grattoni’s team has shown similar promise in implants for delivering chemotherapeutics in a pancreatic cancer model, so the efficacy in this model wasn’t unexpected. "We were more excited than surprised with our results," Grattoni said. From here, the team will determine the lowest dose needed for continued protection, and whether the implant is effective against sexual and IV transmission of the virus, while they prep for clinical trials. “We hope for clinical testing within three years. If all goes well with human trials, we think the implant could be available within five years,” added Grattoni. Learn more about the Grattoni Lab.