Changes in Cerebrospinal Fluid, Liver and Intima-media-thickness Biomarkers in Patients with HIV-associated Neurocognitive Disorders Randomized to a Less Neurotoxic Treatment Regimen

J Neuroimmune Pharmacol. 2023 Dec;18(4):551-562. doi: 10.1007/s11481-023-10086-7. Epub 2023 Oct 31.

Abstract

The prevalence of neurocognitive impairment in people living with HIV is estimated between 30 and 50%. The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. Aim of the study was to measure the change in CSF biomarkers, Fibroscan and IMT measurements in PLWH with HAND randomized to a less neurotoxic regimen, or continuing their treatment. Adult patients with HAND were screened and enrolled if presenting no major resistance associated mutations, no HIV viral replication, not on efavirenz or darunavir, with R5-tropic HIV and without major confounding conditions. Lumbar puncture, IMT and Fibroscan measurements were performed. After 1:1 randomization to a less neurotoxic regimen consisting of darunavir/cobicistat plus emtricitabine plus maraviroc, or mantaining actual care, tests were repeated after 24 weeks: CSF biomarkes (HIV RNA, tau, p-tau, Beta-amyloid1-42, S100Beta and neopterin) were included. Non-parametric tests (Mann-Whitney and Wilcoxon's) were used. 28 participants completed the study. Male and European ancestry were prevalent; median age was 55 years (51-60). All patients were virally suppressed; median CD4 + count was 626 cell/uL (469-772). Baseline characteristics were similar between the study arms. A significant decrease in CSF p-tau and an increase in CSF neopterin and NFL were observed. We observed a significant reduction in liver stiffness at W24. Despite a small sample size we observed changes in neuromarkers and in hepatic stiffness in patients randomized to the experimental arm. We observed changes in CSF biomarkers (lower phosphorylated-tau and higher neopterin and NFL) that need to be replicated in large cohorts. Subclinical neurotoxicity may be observed in patients with HAND and warrants prospective studies.

Trial registration: ClinicalTrials.gov NCT03163277.

Keywords: HAND; Neuromarkers; Neurovirology; Non-invasive tools; PLWH.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid
  • Carotid Intima-Media Thickness*
  • Darunavir
  • Female
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Liver
  • Male
  • Middle Aged
  • Neopterin / cerebrospinal fluid
  • Neopterin / therapeutic use
  • Neurocognitive Disorders / chemically induced
  • Neurocognitive Disorders / diagnostic imaging
  • Neurocognitive Disorders / epidemiology
  • Prospective Studies
  • Viral Load

Substances

  • Biomarkers
  • Darunavir
  • Neopterin

Associated data

  • ClinicalTrials.gov/NCT03163277