Clinical pharmacokinetics of antiretroviral drugs in older persons.

INTRODUCTION: Combination antiretroviral therapy has enabled HIV-infected persons to reach older ages in high numbers. Hepatic and renal changes that normally occur with advancing age occur earlier and with higher incidence in HIV-infected individuals. A limited number of prospective controlled studies have demonstrated small reductions (17 to 41%) in lopinavir, atazanavir and lamivudine clearance in older versus younger adults. A much larger number of retrospective studies in adults (age range ∼ 20 to 60 years), including all antiretroviral drugs, have evaluated age as a covariate for pharmacokinetics. Most studies did not detect substantial associations between drug exposures and age. AREAS COVERED: This review summarizes antiretroviral drug pharmacokinetics in older persons. The authors review articles from PubMed (search terms: elderly, antiretroviral, pharmacokinetics) in addition to the bibliographies of those selected. EXPERT OPINION: The evidence to date does not support major pharmacokinetic changes in adults between ∼ 20 and 60 years of age. However, additional prospective, well-controlled studies are needed in more persons > 60 years, including those with frailty and comorbidities, with assessment of unbound drug clearance, and incorporation of adherence, pharmacogenetics and concomitant medications. Until then, guidelines for drug-drug interactions and dosing in renal and hepatic impairment should be followed in older HIV-infected individuals.