Background
Polypharmacy, or the use of five or more non-ART prescription medications, promote neurologic disorders and geriatric syndromes. However, it is unknown if this is mediated by neuronal damage incurred by multiple medications, by inflammation, or by high comorbidity burden necessitating the use of multiple medications. To better understand how polypharmacy influences neurologic disorder in people with HIV (PWH) we compared polypharmacy, biomarkers of neuronal injury and inflammation, and gait speed and recurrent falls.
Methods
Data and specimens from 600 PWH of the longitudinal AIDS Clinical Trials Group (ACTG) A5322 (HAILO) study were included. Inclusion criteria were plasma HIV RNA below 200 cps/mL at study entry. Neurofilament light chain (NfL) levels were quantified using a single-molecule array assay in duplicate. Neopterin was quantified by ELISA and soluble CD14 (sCD14) was assessed using a bead-based assay (Eve Tech). Multivariable logistic regression analysis was utilized to assess the relationship between polypharmacy and NfL, sCD14, and neopterin (biomarkers of monocyte/microglial cell activation). All biomarkers were analyzed as continuous variables.
Results
Six hundred HAILO participants were included, with median age of 54 years (range 40 to 78); 81% were male sex, 33% were Black Non-Hispanic race, 20% were Hispanic, and 39% with polypharmacy. Higher NfL was associated with male sex (OR 1.18 [1.06, 1.31]), older age (OR 1.52 [1.16, 2.01]), and comorbidity burden (OR for 2 comorbidities: 1.3 [1.13, 1.48]; OR for 3 comorbidities: 1.96 [1.61, 2.39]; OR for 4 comorbidities: 3.23 [2.17, 4.80]). Analyzed comorbidities are CVD, T2 diabetes mellitus, liver disease, kidney disease, and peripheral neuropathy. In multivariable analysis, after adjusting for age, sex, and comorbidity burden, polypharmacy had a modest but significant association with elevated plasma NfL (OR 1.16 [ 1.07, 1.26]), but not with sCD14 or neopterin. Elevated plasma NfL (OR 1.24 [1.05, 1.46]) and plasma sCD14 (OR 1.11 [1.01, 1.22] were associated with recurrent falls (more than one fall in 6 months), but not with slow gait speed.
Conclusions
In older PWH, both polypharmacy and recurrent falls associate with elevated levels of NfL after accounting for comorbidities that could influence the outcomes. These results support other data that polypharmacy contributes to neurologic disorders in older PWH. Medication management may improve brain health and geriatric syndromes in PWH.
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