Drug Abuse and Hepatitis C Infection as Comorbid Features of HIV Associated Neurocognitive Disorder: Neurocognitive and Neuroimaging Features

University of Illinois and Jesse Brown VA Medical Center, Chicago, IL, USA.
Neuropsychology Review (Impact Factor: 4.59). 07/2009; 19(2):215-31. DOI: 10.1007/s11065-009-9101-6
Source: PubMed


Substance abuse and co-infection with hepatitis C (HCV) are two highly relevant determinants of neurocognitive and neuroimaging abnormalities associated with HIV. Substance abuse and HCV are common in the HIV population and there is increasing evidence that the CNS is directly compromised by these comorbid conditions via additive or synergistic processes. In this article we review the current literature regarding mechanisms of neuronal injury as well as the neuropsychological and neuroimaging signatures associated with substance abuse and HCV status among HIV patients. We discuss specific methodological challenges and threats to validity associated with studies of HIV and comorbid substance use disorders or HCV and review potential strategies for minimizing their confounding effects. Efforts to understand the interactions between HIV, substance abuse and HCV co-infection will lead to more complete models of neuropathogenesis of HIV and a greater understanding of the variability in neuropsychological expression of HIV Associated Neurocognitive Disorder.

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Available from: Eileen Martin
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    • "Due to shared methods of transmission, up to 40 % of HIV-infected individuals are co-infected with HCV (Operskalski and Kovacs 2011; Taylor et al. 2012). While effective ART has significantly improved outcomes in co-infected patients, HCV co-infection can further increase innate immune activation, which in turn is associated with higher risk of neurocognitive impairment (Ryan et al. 2004; Letendre et al. 2005; Morgello 2005; Morgello et al. 2005; Parsons et al. 2006; Brew and Letendre 2008; Hinkin et al. 2008; Martin-Thormeyer and Paul 2009; Cohen et al. 2011; Devlin et al. 2012; The Mind Exchange Working Group 2013; Sun et al. 2013). Furthermore, monocyte activation in HIV/HCV co-infected subjects has been shown to correlate with cognitive impairment even in those with suppressed plasma HIV RNA (Rempel et al. 2010; Sun et al. 2013). "
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    ABSTRACT: Despite reduced prevalence of severe forms of HIV-associated neurocognitive disorders (HAND) on current antiretroviral therapy (ART) regimens, milder forms of neurocognitive impairment (NCI) remain prevalent in HIV-infected populations. These mild forms of HAND consist of subtypes, probably reflecting distinct, though possibly overlapping, pathophysiological mechanisms. Factors associated with HAND in HIV patients with prolonged viral suppression on ART include older age, low nadir CD4, active HCV co-infection, and cardiovascular risk factors, but underlying mechanisms and their relationship to innate immune activation, chronic inflammation, and other features of systemic disease are poorly understood. In this article, we discuss applications and limitations of plasma inflammatory biomarkers for studies on HAND in HIV patients on ART and describe an analysis pipeline to reduce common sources of noise and increase likelihood of identifying relevant inflammatory biomarkers. Clinical covariates and comorbidities that influence inflammatory biomarkers, such as aging, obesity, metabolic abnormalities, HCV co-infection, and substance abuse, are also reviewed. As an example for using this analytic pipeline, we present an exploratory study of 22 plasma inflammatory biomarkers (IFN-α 2b and -γ, 16 cytokines/chemokines, sIL-2R, sCD14, HA, and YKL-40) in a cohort of HIV-infected individuals with advanced disease, frequent HCV co-infection, and viral suppression on ART. The identification of inflammatory biomarkers associated with HAND in HIV+ patients on ART may be useful to distinguish between HAND subtypes with distinct pathophysiology, and is important for achieving a systems-level understanding of the biology of these disorders, developing effective therapies, and evaluating therapeutic outcomes. Electronic supplementary material The online version of this article (doi:10.1007/s11481-013-9512-2) contains supplementary material, which is available to authorized users.
    Preview · Article · Nov 2013 · Journal of Neuroimmune Pharmacology
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    • "All of these conditions can have deleterious effect on psychosocial health of the patients. Martin-Thormeyer et al.(73) have reviewed the impact of these comorbidities on the psychosocial health of the patients. Because of similar routes of transmission, up to 90% of patients might have con-infection according to some European series. "
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    ABSTRACT: We briefly reviewed the evidence on the association of hepatitis C (HCV) infection with several aspects of mental and psychosocial health. Medline was searched with appropriate keywords. The primary sources were the systematic reviews. If systematic reviews were not available for a subject, then the most relevant and methodologically sound original studies were selected. HCV infection is associated with poorer health-related quality of life, and physical, mental, and social health. A part of impaired health of these patients is related to cirrhosis, intravenous drug use, co morbid psychiatric disorders, stigmatization, poor social support, alcohol abuse, and interferon treatment. However, HCV itself is also associated with poorer health status particularly in the physical and cognitive domains, which might be related to brain alterations induced by the virus. Interferon treatment is an important cause of depression in HCV patients and sometimes is associated with irritability, manic episode, or acute confusional state. Social health of HCV patients is significantly impaired by stigmatization, poor social support, psychiatric comorbidties, and impaired coping. Psychosocial impairment of HCV patients significantly impairs their treatment adherence. A supportive and nonjudgmental multidisciplinary team is required for optimal management of these patients. Patients with HCV infection had complex neuropsychiatric and psychosocial problems. These problems are challenges for management of HCV infection, affect the patient's care significantly, and might alter the course of the disease. A multidisciplinary approach, a supportive environment, and a nonjudgmental healthcare team are required for optimal medical and psychosocial management of patients with HCV.
    Full-text · Article · Jan 2013 · Hepatitis Monthly
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    • "Searching for the mechanisms of HAND neuropathogenesis, and identifying early indicators and biomarkers of HAND, are central themes of neuroAIDS research. Currently, several factors are useful for identifying individuals who are inherently or chronically at risk for HAND, including demographic characteristics [Becker et al., 2004; Cherner et al., 2004; Valcour et al., 2004b], medical comorbidities [Qureshi et al., 1998; Cherner et al., 2005; Tozzi et al., 2005; Valcour et al., 2005; Lin et al., 2011], and lifestyle behaviors, in particular substance abuse [Rippeth et al., 2004; Levine et al., 2006; Martin-Thormeyer and Paul, 2009]. In addition, host genetic factors have received attention, both as a means to identify risk factors and to determine the neuropathogenesis of HAND. "
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    ABSTRACT: The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. Candidate gene studies have implicated genetic susceptibility loci within immune-related genes; however, these have not been reliably validated. Here, we employed genome-wide association (GWA) methods to discover novel genetic susceptibility loci associated with HAND, and validate susceptibility loci implicated in prior candidate gene studies. Data from 1,287 participants enrolled in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models determined subject-specific slopes for change over time in processing speed and executive functioning, considering all visits including baseline and the most recent study visit. Covariates modeled as fixed effects included: time since the first visit, depression severity, nadir CD4+ T-cell count, hepatitis C co-infection, substance use, and antiretroviral medication regimen. Prevalence of HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also examined as neurocognitive phenotypes in a case-control analysis. No genetic susceptibility loci were associated with decline in processing speed or executive functioning among almost 2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed. No association between the SNPs and HAD or NCI were found. Previously reported associations between specific genetic susceptibility loci, HIV-associated NCI, and HAD were not validated. In this first GWAS of HAND, no novel or previously identified genetic susceptibility loci were associated with any of the phenotypes examined. Due to the relatively small sample size, future collaborative efforts that incorporate this dataset may still yield important findings.
    Full-text · Article · Sep 2012 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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