The Effects of Prescribed Medications on Depressive Symptoms and Neurocognitive Performance in People With HIV

Background: Alterations in brain function and structure, such as depression and neurocognitive impairment, continue to occur in people with human immunodeficiency virus (HIV, PWH) taking suppressive antiretroviral therapy (ART). The lifespan of PWH has improved but the healthspan remains worse than people without HIV, in part because of aging-related diseases. As a result, polypharmacy is common and increases the risk of drug-drug interactions and adverse reactions. Methods: This cross-sectional project investigated the relationship between 7 medication-related metrics (including anticholinergic burden), depressive symptoms, and neurocognitive performance in 491 PWH at a single center in the United States. All participants were taking ART and had plasma HIV RNA ≤ 200copies/mL. Results: Participants had taken ART for a mean of 6.5 years, and most (57.6%) had CD4+ T-cells >500/μL. All 7 medication-related metrics were associated with worse global neurocognitive performance (P value <.0001 to. 0087). Multivariable models confirmed that higher anticholinergic burden (P =. 040) and use of benzodiazepines (P =. 033), antidepressants (P =. 0011), and more total medications (P =. 059) were associated with more depressive symptoms (model P <. 0001). Use of benzodiazepines (P =. 0024) and opiates (P =. 043) along with higher anticholinergic burden (P =. 066) were also associated with worse neurocognitive performance. Benzodiazepine use was associated with worse performance in all domains and opiate use was associated with worse performance in processing speed, motor function, executive function, and working memory. Conclusions: Use of benzodiazepines, opiates, and anticholinergic drugs contribute to cognitive and mood disorders in PWH. When possible, modifying or deprescribing medications may be beneficial.