Beyond Dosing Frequency: Clinical Pharmacology and Pharmacy Optimization of Long-Acting Antiretroviral Therapy in HIV

Long-acting antiretroviral therapy (LA-ART) is an important strategy to decrease the burden of daily oral HIV treatment and provide long-lasting antiretroviral exposure. But there are also unique pharmacokinetic, medication safety, adherence and resistance-related challenges with long-lasting drugs. The clinical pharmacology of LA-ART is explored, with a particular focus on depot-mediated absorption, systemic exposure, dosing intervals, pharmacokinetic tails, drug–drug interactions, patient selection, missed injections, and patient-reported outcomes. The review also explores the scope of clinical pharmacists' involvement in medication reconciliation, interaction screening, eligibility for medication therapies, patient counselling, adherence, monitoring and planning for transition to treatment. A holistic model is suggested that connects drug properties, formulation characteristics, drug exposure (pharmacokinetics), patient behavior, clinical outcomes, and pharmacist intervention. Predictable exposure, resistance prevention, individualized treatment selection, and multidisciplinary implementation should be emphasized in the future development of LA-ART. Therefore, LA-ART optimization should be a combination of pharmacokinetic principles, patient-centred and clinical-pharmacy based approaches.