1. Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection.
- Author
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Young IC, Massud I, Cottrell ML, Shrivastava R, Maturavongsadit P, Prasher A, Wong-Sam A, Dinh C, Edwards T, Mrotz V, Mitchell J, Seixas JN, Pallerla A, Thorson A, Schauer A, Sykes C, De la Cruz G, Montgomery SA, Kashuba ADM, Heneine W, Dobard CW, Kovarova M, Garcia JV, García-Lerma JG, and Benhabbour SR
- Subjects
- Humans, Female, Animals, Mice, Macaca, Pyridones, Rectum, HIV Integrase Inhibitors therapeutic use, Pre-Exposure Prophylaxis methods, HIV Infections prevention & control, HIV Infections drug therapy, Anti-HIV Agents therapeutic use
- 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., (© 2023. The Author(s).)
- Published
- 2023
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