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Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection by 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; S. Rahima Benhabbour is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection about?

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.

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Author

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; S. Rahima Benhabbour

Publisher

Nature Publishing Group UK

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)