Neurocognition in Individuals Co-Infected with HIV and Hepatitis C

David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Room C8-747, Los Angeles, CA 90024, USA.
Journal of Addictive Diseases (Impact Factor: 1.46). 02/2008; 27(2):11-7. DOI: 10.1300/J069v27n02_02
Source: PubMed


Due to similar routes of viral transmission, many individuals infected with the human immunodeficiency virus (HIV) are also infected with the hepatitis C virus (HCV). Each virus can cause cognitive compromise among mono-infected individuals; evidence is accumulating that HIV/HCV co-infection may have a particularly deleterious impact on cognition. We present neuropsychological data obtained from 118 HIV+ adults with advanced HIV disease, 35 of whom were co-infected with HCV, who completed a comprehensive neurocognitive evaluation. Rates of global cognitive impairment were higher among co-infected patients than among those with HIV alone (63% vs. 43%). Within the specific domains of learning and memory, co-infected individuals were significantly more likely to be impaired than were the HIV mono-infected participants. Finally, we discuss implications of these findings and potential future directions for research in this area.

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    • "3% of patients in research studies . However , the subtler forms of HAND remain frequent and become more likely with increasing age ( Devlin et al . , 2012 ; Hargus and Thayer , 2013 ) . In this regard , there are several studies that have investigated potential biomarkers for early detection of neurocognitive impairment in HIV infected patients ( Hinkin et al . , 2008 ; Kusao et al . , 2012 ) while there are very limited studies that have investigated genetic factors that might be affected by HIV infection and / or cocaine abuse ."
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    ABSTRACT: HIV-associated neurological disorder (HAND) has long been recognized as a consequence of human immunodeficiency virus (HIV) infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson's disease) in regulating dopamine (DA) transmission and reactive oxygen species (ROS) production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder. In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC). Gene and protein expression analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry. Effect of DJ1 dysregulation on oxidative stress was analyzed by measuring ROS production in these cells. Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine which is inversely proportional to ROS production. This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1 and/or cocaine indicating oxidative stress level of DA neurons.
    Frontiers in Microbiology 07/2015; 6. DOI:10.3389/fmicb.2015.00749 · 3.99 Impact Factor
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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.
    Journal of Neuroimmune Pharmacology 11/2013; 8(5). DOI:10.1007/s11481-013-9512-2 · 4.11 Impact Factor
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    • "Also, the presence of HIV has a negative impact on the natural history of HCV since the progression to cirrhosis is higher in coinfected [54, 55]. HCV/HIV coinfection is associated to develop other complications, such as hematologic disorders [56, 57], kidney disease [58, 59], cardiovascular disease [60, 61], and neurologic status [62–65]. "
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    ABSTRACT: NATURAL HISTORY OF HCV RELATED CHRONIC HEPATITIS IS INFLUENCED AND MODIFIED BY MANY FACTORS: virus features, coinfections and host characteristics. In particular, a peculiar genetic background of the host by conditioning the occurrence of intracellular metabolic derangements (i.e., insulin resistance) might contribute to accelerate the rate of progression to cirrhosis and eventually the occurrence of hepatocellular carcinoma (HCC) and death. Likely, direct interplays between virus genotype and host genetic background might be hypothesized at this level. Morbidity and mortality in cirrhosis is primarily associated with complications of liver cirrhosis (ascites, hepatic encephalopathy, jaundice, and gastroesophageal bleeding) and HCC occurrence. Therefore the main goal of therapy is to clear viral infection and decrease liver necro-inflammation that directly relates to development of cirrhosis and HCC. Among patients treated with Interferon-based therapy, those with sustained viral response showed a significant reduction of progression to cirrhosis and development of HCC. However, a residual risk of hepatocellular carcinoma still remains indicating the need for careful follow-up using ultrasonography every six months in cirrhotic patients, even in those showing persistently normal ALT and undetectable HCV RNA levels after antiviral therapy.
    11/2011; 2011:314301. DOI:10.4061/2011/314301
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