{"doi":"10.1111/jgs.17569","title":"Polypharmacy in older adults with HIV infection: Effects on the brain","abstract":"Over the past decade, antiretroviral therapy (ART) has substantially evolved so that the medications are safer, much more potent, and require less frequent dosing than early in the pandemic. Widespread use of ART has led to a dramatic decline in opportunistic complications and mortality associated with acquired immunodeficiency syndrome (AIDS), and as a result, the survival of people with HIV (PWH) is approaching that of the general population. As PWH age, however, they are spending more years of life contending with the long-term health issues associated with aging and with age-related comorbidities that typically occur in the geriatric population. In other words, their healthspan has not improved to the same extent as their lifespan. This has led to a higher burden of non-antiretroviral medications used to treat these comorbidities in PWH than persons without human immunodeficiency virus (HIV). PWH are developing age-related comorbidities more frequently and at earlier ages than the general population.1, 2 Among the age-related comorbidities that are most pronounced in PWH are cardiovascular disease, impaired renal function, impaired neurocognitive function, and neuropathy/distal neuropathic pain.1, 3, 4 The reasons for this are likely multifactorial and may be due in part to the acceleration of immunological and biological age by HIV. The phenomenon of premature epigenetic aging in PWH appears to be pronounced in the brain: Horvath and Levine demonstrated that HIV infection accelerates biological age by 7 years in brain tissue from autopsy and by 5 years in blood.5 Alongside this rise in age-related multimorbidity is an increase in polypharmacy, typically defined as use of at least five medications. PWH take more medications than those without HIV, even when excluding ART.6-9 A recent study on PWH older than 60 years found that polypharmacy occurred in 65% of adults in this population.10 Likewise, emerging data from the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) Study, Medicare claims, and from the Multicenter AIDS Cohort Study all demonstrate consistently more frequent polypharmacy among PWH compared with uninfected controls, even when excluding ART from the medication counts.6-8 Polypharmacy is thus a special challenge for older PWH, placing them at high risk for drug–drug interactions (DDIs) and potentially inappropriate medication use, and for poor clinical outcomes including falls, hospitalizations, and increased mortality. In older adults without HIV infection, polypharmacy is strongly linked with adverse clinical outcomes, including increased hospitalization and falls.11 “Hyperpolypharmacy,” or the use of at least 10 medications, is further associated with cognitive decline.12 Among virally suppressed PWH aged 45–65 years in Colorado, Erlandson et al. likewise found that polypharmacy was associated with frailty, slower 400 meter walk time, and poorer performance on the Short Physical Performance Battery.13 In PWH, each additional prescribed medication is associated with a 40% higher risk for falls.14 The association between polypharmacy in PWH and poor outcomes, including frailty and hospitalizations, is also present in resource-limited settings.15 Among the potential poor outcomes associated with polypharmacy, neurological impairment is of particular concern in PWH. Multiple studies have demonstrated an excess of cognitive impairment in PWH despite adequate virologic suppression, with impairment affecting multiple domains including episodic memory, motor function, information processing, and executive functioning. While this higher baseline risk is likely multifactorial, HIV and aging seem to synergistically contribute to neurological dysfunction, with HIV accelerating deleterious effects on specific neurocognitive domains commonly associated with aging.3 HIV-associated neurologic dysfunction may be especially exacerbated by the frequent use of psychoactive medications in PWH. Women with ","journal":"Journal of the American Geriatrics Society","year":2021,"id":180795,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":371983,"name":"Scott Letendre","orcid":"0000-0003-3490-4975","position":1,"is_corresponding":false},{"id":242505,"name":"Kristine M. Erlandson","orcid":"0000-0003-0808-6729","position":2,"is_corresponding":false},{"id":513184,"name":"Qing Ma","orcid":"0000-0003-0123-9913","position":3,"is_corresponding":false},{"id":371984,"name":"Ronald J. Ellis","orcid":"0000-0003-4931-752X","position":4,"is_corresponding":false},{"id":105836,"name":"Shelli Farhadian","orcid":"0000-0001-7230-1409","position":5,"is_corresponding":false},{"id":730365,"name":"Lauren Smith","orcid":"0000-0003-2625-1281","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-18T23:47:57.268805Z","pmid":"34855982","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}