The selection of highly active antiretroviral therapy for treatment-naive HIV-infected individuals is complex. In addition to patient adherence, exposures of antiretroviral agents (ARVs) can be influenced by patient population, gender, drug–drug and drug–food interactions, and comorbid medical conditions. In contrast to pharmacokinetic sampling performed under controlled conditions, ARV exposures in “real-world” clinical practice display substantial interpatient variability. The interactions between ARVs and other medications commonly used by HIV-infected patients could significantly impact ARV exposures and need to be considered when selecting therapies. Pharmacogenomic differences have been identified for a number of ARVs, resulting in increased plasma exposures (efavirenz, nelfinavir) or increased risk for adverse drug events (atazanavir, abacavir, indinavir). Despite increasing populations of HIV-infected females and people 50 years or older, the pharmacokinetics of many ARVs has not been adequately studied in these patient populations. The clinical significance of many of these pharmacokinetic differences is unknown.
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