A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication

J Neurovirol. 2017 Apr;23(2):216-225. doi: 10.1007/s13365-016-0490-z. Epub 2016 Nov 4.

Abstract

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

Keywords: CD4/CD8 ratio; CPE score; HIV-associated neurocognitive disorders; Immune activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / diagnosis
  • AIDS Dementia Complex / immunology*
  • AIDS Dementia Complex / pathology
  • AIDS Dementia Complex / virology
  • Adult
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacokinetics*
  • Biomarkers / analysis
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / immunology*
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / virology
  • Female
  • HIV / pathogenicity
  • HIV / physiology*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuropsychological Tests
  • Permeability
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Virus Replication

Substances

  • Antiviral Agents
  • Biomarkers