Longitudinal effects of polypharmacy on cognitive function in people with HIV

Objective: – To investigate the relationship of polypharmacy exposure to longitudinal trajectories of global and domain-specific cognitive function in people with HIV (PWH), focusing on the effects of both stable and transitioning polypharmacy regimens.Design: – Longitudinal analyses. Methods: – Longitudinal data from 2173 PWH, including 1017 virally suppressed (VS-PWH), were analyzed using harmonized datasets from the CHARTER, NNTC, and HNRP studies. Polypharmacy was categorized as low (0–4 medications), moderate (5–9), or high (≥10) based on the number of nonantiretroviral therapy (non-ART) medications. Demographically adjusted global and domain-specific T-scores were derived from standardized batteries. To assess the association between polypharmacy and cognitive trajectories, we developed a novel transition-based mixed-effects regression approach that captured both stable and changing patterns of polypharmacy exposure over time, allowing for the assessment of immediate and cumulative cognitive effects of medication burden. Results: – Higher polypharmacy levels were significantly associated with poorer global and domain-specific cognitive function. Participants with high polypharmacy exhibited steeper cognitive declines, while those with low polypharmacy demonstrated stable or modestly improved trajectories. This pattern was similarly observed in VS-PWH. Transitions from low to high polypharmacy resulted in significant global and domain-specific cognitive declines. Conversely, reductions from moderate or high to lower polypharmacy levels yielded cognitive improvements – particularly in motor function – in both PWH and VS-PWH populations. Conclusion: – Polypharmacy imposes a cumulative burden on cognitive function in both PWH and VS-PWH. Higher polypharmacy levels exacerbate cognitive decline, highlighting the necessity of targeted strategies to manage polypharmacy and mitigate its long-term cognitive impact.