Longitudinal effects of polypharmacy on cognitive function in people with HIV

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.

Longitudinal analyses.

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.

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.

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.