Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Winston, Alan; Garvey, Lucy; Scotney, Elizabeth; Yerrakalva, Dharani; Allsop, Joanna; Thomson, Emma C.; Grover, V. P. B.; Main, Janice; Cox, I. Jane; Wylezińska, M; Taylor‐Robinson, Simon D.

doi:10.1111/j.1365-2893.2009.01198.x

Cited by 25 publications

(21 citation statements)

References 40 publications

(56 reference statements)

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“…The impact of HCV disease on NC impairment has been suggested by several studies (Clifford et al 2005; Letendre et al 2005; Garvey et al 2012; Thiyagarajan et al 2010; Vivithanaporn et al 2012; Winston et al 2010). HCV disease might lead to NC impairment either directly (e.g., via infection of glial cells and production of viral proteins) or indirectly (e.g., via upregulated HIV replication and immune activation or substance use disorders that predispose to HCV transmission).…”

Section: Discussionmentioning

confidence: 98%

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

et al. 2015

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Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n=272, mean duration 17.9 months) or LPV/r (n=173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p<0.001), were less likely to have AIDS (p<0.001) or hepatitis C virus (HCV) coinfection (p<0.05), had higher CD4+ T cell nadirs (p<0.001), had lower peak (p<0.001) and current (p<0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p<0.001). Overall, EFV users had worse speed of information processing (p=0.04), verbal fluency (p=0.03), and working memory (p=0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n=329), EFV users performed poorly, whereas among HCV seropositives (n=116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n=269), EFV users had worse speed of information processing (p=0.02) and executive functioning (p=0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial.

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Section: Discussionmentioning

confidence: 98%

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

et al. 2015

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“…RNA profiling and protein expression studies demonstrate that the HCV entry factors are expressed in a variety of tissues, albeit with an increased expression in the liver 16,17 . Reports of cognitive defects and nuclear magnetic resonance abnormalities in HCV infected patients 18-21 led us to screen a series of neural and brain-derived cell lines for their ability to support HCV entry and replication. We found two independently derived neuroepithelioma cell lines which support HCVpp infection.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C Virus Infection of Neuroepithelioma Cell Lines

et al. 2010

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Background & Aims Hepatitis C virus (HCV) establishes chronic infections in 3% of the world's population. Infection leads to progressive liver disease; hepatocytes are the major site of viral replication in vivo. However, chronic infection is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. We therefore screened a series of neural and brain-derived cell lines for their ability to support HCV entry and replication. Methods We used a panel of neural-derived cell lines, HCV pseudoparticles (HCVpp), and an infectious, HCV JFH-1 cell-culture system (HCVcc) to assess viral tropism. Results Two independently derived neuroepithelioma cell lines (SK-N-MC and SK-PN-DW) permitted HCVpp entry. In contrast, several neuroblastoma, glioma, and astrocytoma cell lines were refractory to HCVpp infection. HCVcc infected the neuroepithelioma cell lines and established a productive infection. Permissive neuroepithelioma cells expressed CD81, scavenger receptor BI (SR-BI), and the tight junction proteins Claudin-1 (CLDN1) and occludin, whereas non-permissive neural cell lines lacked CLDN1 and in some cases SR-BI. HCVpp infection of the neuroepithelioma cells was neutralized by antibodies to CD81, SR-BI, CLDN1 and HCV E2. Furthermore, anti-CD81, interferon and the anti-NS3 protease inhibitor VX-950 significantly reduced HCVcc infection of neuroepithelioma and hepatoma cells. Conclusions Neuroepithelioma-derived cell lines express functional receptors that support HCV entry at comparable levels to that of hepatoma cells. HCV infection in vitro is not restricted to hepatic-derived cells, so HCV might infect cells of the CNS in vivo.

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“…Up to 25% of HIV+ individuals are coinfected with hepatitis C (HCV) (Kim et al 2013), and studies within our research group and others suggest deleterious impact of comorbid HCV on cognition (Devlin et al 2012; Rempel et al 2013; Sun et al 2013) and cytokine predictors of cognition (Cohen et al 2011). Evidence has accumulated for impact of HCV coinfection on brain structure (Jernigan et al 2011; Pfefferbaum et al 2012) and brain metabolism (Forton et al 2001; Taylor et al 2004; Winston et al 2010; Garvey et al 2012). However, functional neural consequences of HIV/HCV coinfection during active tasks have not been explored.…”

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confidence: 99%

Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals

et al. 2014

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Cognitive and functional neural correlates of Human Immunodeficiency Virus (HIV) are only partially understood at present. Variability in neural response, which has been noted in the literature, may relate to clinical factors associated with HIV, including time since HIV diagnosis, (CD4) count and nadir, HIV viral load, and comorbid infectious processes, especially hepatitis C. The present investigation evaluated working memory-related functional neural activation in 26 HIV+ participants, 28 demographically matched HIV-seronegative individuals, and 8 HIV+ individuals with hepatitis C coinfection. Analyses examined impact of HIV infection duration, CD4 count and nadir, HIV viral load, and hepatitis C serostatus. Results showed that HIV- participants had fastest reaction times, and during the working memory task HIV+ participants with hepatitis C coinfection showed strongest bias toward commission errors; however, signal detection (i.e., overall task performance) was equivalent across groups. Functional magnetic resonance imaging (FMRI) results showed HIV-related greater activation to an easier vigilance task and HIV-related lower activation to a more difficult working memory task, consistent with reduced cognitive reserve. Hepatitis C coinfection related to diffuse neural dysregulation. Correlational analyses suggested relationships of increasingly severe disease with poorer functioning in brain regions linked to error monitoring and attention regulation.

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Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Cited by 25 publications

References 40 publications

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

Hepatitis C Virus Infection of Neuroepithelioma Cell Lines

Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals

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