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

Nat Commun. 2023 Feb 9;14(1):708. doi: 10.1038/s41467-023-36330-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-HIV Agents* / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • HIV Integrase Inhibitors* / therapeutic use
  • Humans
  • Macaca
  • Mice
  • Pre-Exposure Prophylaxis* / methods
  • Pyridones
  • Rectum

Substances

  • cabotegravir
  • Pyridones
  • HIV Integrase Inhibitors
  • Anti-HIV Agents