Among people living with HIV (PLWH), worsening neuropathic pain may be a signal for neurocognitive impairment and should be investigated. These findings, from a prospective, observational study, were published in Brain.
The CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) study was performed at 6 sites in the United States between 2003 and 2019. Study participants (N=385) were evaluated at baseline and at 12-year follow-up. Examinations included assessment for neuropathy and neuropathic pain, neurocognitive testing, assessment of overall quality of life and general health, and laboratory examination.
Approximately one-quarter of the study population were women. Mean age of the study participants was 43.5±7.81 years, 44.9% were Black, mean years of education attained was 13.1±2.62, 73.8% were on antiretroviral therapy (ART), 45.8% had <50 HIV RNA copies/mL, 70.8% had lifetime substance use disorder, mean Medical Outcomes Study HIV (MOS-HIV) pain function score was 64.2±27.2, mean MOS-HIV physical health summary score was 45.0±11.8, and mean MOS-HIV mental health summary score was 50.3±11.2.
At baseline, 29.9% of PLWH had distal neuropathic pain (DNP); at follow-up, 25.5% had incident (n=65) or worsening (n=33) DNP.
Results of neurocognitive assessments conducted at follow-up revealed greater declines in speed of information processing (mean difference [MD], -0.534 vs -0.122; P =.0003), executive function (MD, -0.499 vs -0.206; P =.0095), and motor function (MD, -1.05 vs -0.789; P =.0414) among individuals experiencing incident or worsening DNP compared with the others, respectively. In addition, incident or worsening DNP was associated with worse MOS-HIV pain function scores (mean, 52.7 vs 68.0; P =1.89 x 10-6) and poorer balance (P =.0002).
Change in neurocognitive performance was correlated with baseline Beck Depression Inventory (BDI-II) scores (r, -0.181; P =.0003) and incident diabetes (MD, -0.476 vs -0.241; P =.0127).
In a multivariable model, both lower BDI-II score at baseline (P =.00048) and incident or worsened DNP (P =.0221) were found to be predictive of neurocognitive decline (P =.122 x 10-4). In another model, incident or worsened DNP (P =.00946) and incident diabetes (P =.01436) did not have a significant interaction (P =.06194) to predict cognitive decline (P =.0060).
The major limitation of this study was that it was not designed to evaluate causal relationships between pain and cognition.
Study authors concluded, “We showed that those with DNP at baseline performed no worse than those without; the same was true for the follow-up visit. DNP and other sensory disturbances did, however, associate with poor performance on the test of motor functioning, specifically. Future clinical trials to reduce pain and assess the impact of this intervention on neurocognitive performance would provide insight into causality. If an individual reports incident DNP, they may also have or be at increased risk for cognitive difficulties and associated medication nonadherence, virologic failure, reduced independence in instrumental activities of daily living and reduced quality of life.”
Ellis RJ, Sacktor N, Clifford DB, et al; for the CNS Antiretroviral Therapy Effects Research (CHARTER) Study Group. Neuropathic pain correlates with worsening cognition in people with human immunodeficiency virus. Brain. 2022;145(6):2206-2213. doi:10.1093/brain/awab462