Dual drivers of polypharmacy in people with HIV: Quantifying the independent associations of aging and long‐term antiretroviral therapy

Objectives This study aimed to disentangle the independent effects of aging and cumulative antiretroviral therapy (ART) duration on polypharmacy in people with HIV. While successful ART has led to an aging population with HIV, polypharmacy may stem from both aging and ART's cumulaftive toxicity. Quantitative evidence separating these effects is scarce, particularly in Japan. Methods In this retrospective study, we analysed a Japanese community pharmacy database (2014–2022) of 696 people on ART for ≥6 months. Using negative binomial regression, we assessed the independent effects of age and cumulative ART duration on the number of concomitant medications (a proxy for polypharmacy), adjusting for sex. Results Both advanced age and cumulative ART duration were significant independent risk factors for polypharmacy. A strong dose‐dependent relationship was observed with age (incidence rate ratio [IRR] for 60–69 years: 9.61; 95% confidence interval [CI], 4.92–18.78 vs. <30 years). After adjusting for age and sex, a cumulative ART duration of ≥9 years remained an independent predictor of more concomitant medications (IRR: 1.81; 95% CI, 1.05–3.13 vs. <1 year). Conclusions We propose a “dual‐structure model” for polypharmacy in people with HIV, comprising age‐related multimorbidity and a distinct layer potentially linked to the long‐term effects of ART. To our knowledge, this study provides the first quantitative evidence from Japan to statistically disentangle the associations with these two factors. Our findings highlight the need to integrate geriatric principles with HIV‐specific toxicity management for optimal long‐term strategies.