Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition

AIDS. 2023 May 1;37(6):957-966. doi: 10.1097/QAD.0000000000003494. Epub 2023 Jan 25.

Abstract

Objective: HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines.

Design: Systematic review and meta-analysis.

Methods: We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resistance, pregnancy-related adverse events, and sexual behavior. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively.

Results: We identified 12 articles/abstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval: 0.07-0.61), resulting in a 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior.

Conclusions: CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies; more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • Humans
  • Male
  • Pre-Exposure Prophylaxis* / methods
  • Pyridones / therapeutic use
  • Randomized Controlled Trials as Topic

Substances

  • cabotegravir
  • Anti-HIV Agents
  • Pyridones