1. Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
- Author
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Isabella C. Young, Ivana Massud, Mackenzie L. Cottrell, Roopali Shrivastava, Panita Maturavongsadit, Alka Prasher, Andres Wong-Sam, Chuong Dinh, Tiancheng Edwards, Victoria Mrotz, James Mitchell, Josilene Nascimento Seixas, Aryani Pallerla, Allison Thorson, Amanda Schauer, Craig Sykes, Gabriela De la Cruz, Stephanie A. Montgomery, Angela D. M. Kashuba, Walid Heneine, Charles W. Dobard, Martina Kovarova, J. Victor Garcia, J. Gerardo Garcίa-Lerma, and S. Rahima Benhabbour
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans.
- Published
- 2023
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