Long-Acting Injectable Antiretroviral Therapies for HIV Treatment and Prevention: Clinical Pharmacology, Recent Advances and Future Opportunities.

Long-acting (LA) antiretroviral (ARV) medications represent a significant advancement in the HIV treatment and prevention field. LA ARVs help reduce daily pill burden and thus optimize adherence, which has translated into sustained virologic suppression in persons with HIV, prevention of HIV transmission among those at risk, and improved patient satisfaction. This review examines the clinical pharmacology considerations, clinical trials, and real-world use of small molecule LA injectable ARVs, specifically cabotegravir, rilpivirine, and lenacapavir, in adults with or at risk of acquiring HIV, with a particular focus on the pharmacokinetic data and considerations with these agents as implementation expands. Special attention is also paid to understudied populations such as pediatrics and pregnant and breastfeeding women. Discussion of the underlying pharmacokinetics is provided to highlight considerations regarding time to onset of protection, handling residual concentrations and the potential for the development of resistance with treatment discontinuation, factors contributing to variability in drug exposure and relationships between exposure and efficacy. Despite the promise that these LA injectable ARVs hold, there are still opportunities for further investigation to optimize patient care, and these considerations are also covered.