Principles of Applied Clinical Pharmacokinetics and Pharmacodynamics in Antiretroviral Therapy

Systemic concentrations of antiretroviral drugs (ARVs) are influenced by the pharmacokinetic properties of absorption, distribution, metabolism, and excretion. Pharmacokinetics and local drug exposure can differ significantly within anatomical sanctuary sites compared with the systemic compartment. High variability in interpatient ARV concentrations is common, which makes population pharmacokinetics for ARVs very difficult to interpret. HIV replication is dynamic and requires combination antiretroviral therapy with multiple active agents in order to achieve durable virologic suppression. Direct and indirect relationships between drug exposure, efficacy, and/or toxicity are common for most ARVs, which can be used to improve overall treatment success. Suboptimal adherence can result in inadequate concentrations, drug resistance, and virologic failure. Therapeutic drug monitoring can be considered in certain scenarios that should be evaluated on a case-by-case basis.