Click to scroll back to the topClick to go to previous articleClick to go to next article
Follow us
Copyright 2024. Houston Methodist, Houston, TX. All rights reserved.
Outcomes Research

PrEPping for the Future

Researchers advance the future of HIV prevention with PrEP-eluting, refillable, nanofluidic implants.

The HIV epidemic remains a significant public health problem globally and in the United States, especially in the South.
In the most recent surveillance report, the Center for Disease Control notes that the South has the highest number of people living with HIV and, in 2021, accounted for more than half of new U.S. cases.
Pre-exposure prophylaxis, or PrEP, is a critical tool in fighting the HIV epidemic. In those who are at risk from sexual or intravenous drug use transmission, PrEP provides up to 99% protection when taken as directed. According to the first-ever study on state-level PrEP use, the South accounted for 52% of HIV diagnoses but only 39% of PrEP users.
Share this story
The imbalance of PrEP use in the South comes down to health disparities exacerbated by barriers to consistent access. The regimen requires either daily oral intake or bi-monthly injections from a health care provider and missing even one dose can have dire consequences. While increasing access for underserved communities is crucial, developing a more practical, low-maintenance PrEP regimen would significantly advance equitable PrEP access. Long-acting delivery systems that could increase PrEP uptake and persistence may be the answer.
Alessandro Grattoni, PhD
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.
Our goal was to find a fool-proof delivery mechanism that would be easier and more convenient to use for patients who have trouble adhering to a daily oral pill regimen or bi-monthly injection schedule.
Alessandro Grattoni, PhD
Chair of the Department of Nanomedicine
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.
Fernanda P. Pons-Faudoa, Nicola Di Trani, Simone Capuani, Jocelyn Nikita Campa-Carranza, Bharti Nehete, Suman Sharma, Kathryn A. Shelton, Lane R. Bushman, Farah Abdelmawla, Martin Williams, Laura Roon, David Nerguizian, Corrine Ying Xuan Chua, Michael M. Ittmann, Joan E. Nichols, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Alessandro Grattoni
Heather Lander, PhD
October 2023
Share this story