PLoS ONE (Jan 2012)

Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation.

  • Lucy J Garvey,
  • Nicola Pavese,
  • Anil Ramlackhansingh,
  • Emma Thomson,
  • Joanna M Allsop,
  • Marios Politis,
  • Ranjababu Kulasegaram,
  • Janice Main,
  • David J Brooks,
  • Simon D Taylor-Robinson,
  • Alan Winston

DOI
https://doi.org/10.1371/journal.pone.0038980
Journal volume & issue
Vol. 7, no. 7
p. e38980

Abstract

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BackgroundMicroglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.MethodsA case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) using a (11)C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.ResultsTwenty-four aHCV cases completed NCT and (1)H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent (1)H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on (1)H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in (11)C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.DiscussionPoorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher (11)C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.