Acute HCV/HIV Coinfection Is Associated with Cognitive Dysfunction and Cerebral Metabolite Disturbance, but Not Increased Microglial Cell Activation

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

doi:10.1371/journal.pone.0038980

Abstract

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 (1H-MRS) and positron emission tomography (PET) using a 11C-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 1H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent 1H-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 1H-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 11C-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 11C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.

Highlights

Central nervous system disturbances are well described in patients with chronic Human-Immune-Deficiency viral (HIV) infection and more recently, in those with chronic hepatitis C (HCV) infection in the absence of significant liver disease[1,2,3]
When factors associated with poorer executive function were examined in a multivariate model, no association with receiving combination antiretroviral therapy (cART) was observed (p = 0.37, 95%CI 218.8, 7.1), lower nadir CD4+ cell count and aHCV study group were independently associated with poorer executive function performance (Table 3)
We have demonstrated that acquisition of acute hepatitis C viral (HCV) in HIV-infected subjects is associated with changes in cerebral function measures using a cognitive assessment and cerebral 1H-MRS

Summary

Introduction

Central nervous system disturbances are well described in patients with chronic HIV infection and more recently, in those with chronic hepatitis C (HCV) infection in the absence of significant liver disease[1,2,3]. Abnormalities, compared to matched control populations, demonstrable using cerebral function measures such as neurocognitive testing (NCT) and proton magnetic resonance spectroscopy (1H MRS) have been shown in both patient groups [4,5]. Such cerebral deficits may be greater in individuals coinfected with HIV and chronic HCV, compared to individuals with HIV monoinfection [6,7,8,9]. 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

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