Micro-structural brain alterations in aviremic HIV+ patients with minor neurocognitive disorders: a multi-contrast study at high field

PLoS One. 2013 Sep 10;8(9):e72547. doi: 10.1371/journal.pone.0072547. eCollection 2013.

Abstract

Objective: Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective combination antiretroviral therapy (cART). In this study, we used an innovative multi-contrast magnetic resonance imaging (MRI) approach at high-field to assess the presence of micro-structural brain alterations in MND+ patients.

Methods: We enrolled 17 MND+ and 19 MND- patients with undetectable HIV-1 RNA and 19 healthy controls (HC). MRI acquisitions at 3T included: MP2RAGE for T1 relaxation times, Magnetization Transfer (MT), T2* and Susceptibility Weighted Imaging (SWI) to probe micro-structural integrity and iron deposition in the brain. Statistical analysis used permutation-based tests and correction for family-wise error rate. Multiple regression analysis was performed between MRI data and (i) neuropsychological results (ii) HIV infection characteristics. A linear discriminant analysis (LDA) based on MRI data was performed between MND+ and MND- patients and cross-validated with a leave-one-out test.

Results: Our data revealed loss of structural integrity and micro-oedema in MND+ compared to HC in the global white and cortical gray matter, as well as in the thalamus and basal ganglia. Multiple regression analysis showed a significant influence of sub-cortical nuclei alterations on the executive index of MND+ patients (p = 0.04 he and R² = 95.2). The LDA distinguished MND+ and MND- patients with a classification quality of 73% after cross-validation.

Conclusion: Our study shows micro-structural brain tissue alterations in MND+ patients under effective therapy and suggests that multi-contrast MRI at high field is a powerful approach to discriminate between HIV+ patients on cART with and without mild neurocognitive deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Basal Ganglia / pathology
  • Case-Control Studies
  • Cerebral Cortex / pathology*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / virology
  • Discriminant Analysis
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / pathology*
  • HIV-1 / genetics*
  • Humans
  • Linear Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Thalamus / pathology

Substances

  • Anti-HIV Agents
  • RNA, Viral

Grant support

Funding provided by Centre d’Imagerie BioMédicale of the University of Lausanne, the Swiss Federal Institute of Technology Lausanne, the University of Genève, the Centre Hospitalier Universitaire Vaudois, the Hôpitaux Universitaires de Genève, the Leenaards, the Jeantet and the Stoicescu foundations, the Swiss National Science Foundation Grant PZ00P3_131914/11 and FNS 320030_138411, the Swiss HIV Cohort Study, and unrestricted grants from Abbott and ViiV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.