Injectable long-acting pre-exposure prophylaxis for HIV prevention: advancements and future directions in pharmacotherapy.

INTRODUCTION

Long-acting (LA) injectable pre-exposure prophylaxis (PrEP) expands HIV prevention choice beyond daily oral tenofovir-based regimens and may improve persistence by decoupling protection from daily pill-taking.

AREAS COVERED: We provide a clinical-focused narrative review of intramuscular cabotegravir LA (CAB-LA) and subcutaneous lenacapavir (LEN), summarizing pivotal randomized trials, key pharmacology, safety, resistance and HIV testing considerations, and early implementation experience. Evidence was identified through targeted searches of PubMed, major HIV conference proceedings, WHO and CDC guidance, and trial registries (ClinicalTrials.gov) through February 2026.

EXPERT OPINION: Bi-monthly CAB-LA and twice-yearly LEN are both highly efficacious, but scale-up will depend on simplified testing pathways, reliable supply, acceptability, and delivery models that minimize clinic burden. Over the next five years, semiannual and potentially annual PrEP dosing could shift PrEP from 'medication adherence' to 'service access,' enabling integration with sexual health and reproductive services and improving equity if implementation and procurement issues are addressed.