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HCV and HIV co-infection: mechanisms and management.

ABSTRACT: HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS-related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut and leads to an impairment of HCV-specific immune responses. Treatment of HIV with antiretroviral therapy and treatment of HCV have independently been shown to delay the progression of fibrosis and reduce complications from end-stage liver disease among co-infected patients. However, rates of sustained virologic response with PEG-IFN and ribavirin have been significantly inferior among co-infected patients compared with HCV-monoinfected patients, and treatment uptake has remained low given the limited efficacy and tolerability of current HCV regimens. With multiple direct-acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.

SUBMITTER: Chen JY

PROVIDER: S-EPMC4330991 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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HCV and HIV co-infection: mechanisms and management.

Chen Jennifer Y JY Feeney Eoin R ER Chung Raymond T RT

Nature reviews. Gastroenterology & hepatology 20140218 6

HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS-related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apopt ...[more]

PMID: 24535328

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Project description:BackgroundA relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection.MethodsA total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry.ResultsNK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses.ConclusionsOur data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

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HCV and HIV co-infection: mechanisms and management.

Publications

HCV and HIV co-infection: mechanisms and management.

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