Preventing drug interactions with antiretrovirals in the aging HIV population: focusing on population pharmacokinetic modeling

INTRODUCTION: As people with HIV live longer given the success of antiretroviral therapy, the population of older individuals with HIV is rapidly expanding, bringing new challenges related to aging, multimorbidity, and polypharmacy. Age-associated physiological changes - including alterations in renal and hepatic function, body composition, plasma protein binding, and gastrointestinal absorption - can substantially influence drug pharmacokinetics (PK). In individuals with HIV, these changes may be further compounded by chronic inflammation, immune activation, and long-term antiretroviral exposure. Older adults remain underrepresented in clinical pharmacology studies, and dosing recommendations are often extrapolated from younger populations without adequate evaluation of age-specific variability. AREAS COVERED: This paper reviews the application of population PK modeling to better characterize drug disposition in older individuals with HIV. Data was drawn from an extensive literature review of published papers, conference abstracts and data from approved prescribing information sourced from PubMed, Google, and Google Scholar available between 30 June 1980 and 1 August 2026. EXPERT OPINION: Improved pharmacometrics characterization in aging populations with HIV is essential to guide evidence-based prescribing and support safer, more effective long-term management. PBPK models should also be developed and validated for groups that are underrepresented in clinical PK studies given the diversity of older people with HIV.