Updated clinical pharmacologic considerations for HIV-1 protease inhibitors

Abstract

Many data associate low protease inhibitor plasma concentrations with suboptimal virologic responses, whereas fewer data associate high plasma concentrations with toxicity. Knowledge of relationships between concentrations and virologic response is important because significant variability in concentrations exists among patients. For antiretroviral-naïve patients, target trough concentrations have been suggested on the basis of retrospective associations with virologic responses. Two prospective studies demonstrated improved virologic responses when indinavir and nelfinavir doses were managed based on these troughs. Investigations among antiretroviral-experienced patients have identified a relationship between the trough concentration and the in-vitro susceptibility of the patient's virus with virologic outcome. However, differences in virologic response may further depend on other pharmacologic factors, such as protein binding, intracellular kinetics, function of drug transporters, and the activity of other drugs in the regimen. In the future, dosing strategies that accommodate the variability in pharmacokinetics and pharmacodynamics may improve virologic outcomes.