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- Title
Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection.
- Authors
Young, Isabella C.; Massud, Ivana; Cottrell, Mackenzie L.; Shrivastava, Roopali; Maturavongsadit, Panita; Prasher, Alka; Wong-Sam, Andres; Dinh, Chuong; Edwards, Tiancheng; Mrotz, Victoria; Mitchell, James; Seixas, Josilene Nascimento; Pallerla, Aryani; Thorson, Allison; Schauer, Amanda; Sykes, Craig; De la Cruz, Gabriela; Montgomery, Stephanie A.; Kashuba, Angela D. M.; Heneine, Walid
- 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. In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques.
- Subjects
MACAQUES; PRE-exposure prophylaxis; INTEGRASE inhibitors
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36330-5