Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy

Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland.
Gut (Impact Factor: 14.66). 09/2010; 59(9):1252-8. DOI: 10.1136/gut.2009.205971
Source: PubMed

ABSTRACT Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.
To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.
T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals.
The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02).
Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.

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Available from: Huldrych F Günthard, Sep 29, 2015
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    • "There is emerging evidence that successful antiviral treatment of HIV infection and HCV infection may reduce the risk of liver disease progression to cirrhosis and of its complications [1] [16]. Suppression of HIV replication , leading to immune restoration and reduction in systematic inflammation, may slow liver disease progression [17] [18] [19] [20] [21] [22]. As such, expert guidelines recommend antiretroviral therapy for most HIV/HCV coinfected persons, regardless of CD4 cell count [9] [23] [24]. "
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    Journal of Hepatology 11/2014; 61(1). DOI:10.1016/j.jhep.2014.08.006 · 11.34 Impact Factor
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    • "Hepatitis C virus (HCV) is a major cause of severe liver disease and efficiently establishes persistent infections. Data suggest that a specific T cell response is essential for clearance1,2 and control of HCV.3,4,5 Factors correlated to chronicity are a high degree of genetic variability6,7 and HCV proteins which impair the host response.8 The specific T cell response is impaired and/or dysfunctional during chronic infection.9,10,11 "
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    Molecular Therapy 06/2013; 21(9). DOI:10.1038/mt.2013.119 · 6.23 Impact Factor
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    • "This is supported by the fact that CD4 cell counts were significantly higher in patients with effective ART, i.e. with undetectable plasma HIV RNA. Thus, these findings may explain in part the positive effect of antiretroviral therapy on the evolution of liver disease caused by chronic hepatitis C (Rohrbach et al., 2010) . "
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    ABSTRACT: The influence of HIV coinfection on plasma hepatitis C virus (HCV) RNA load has not been reliably evaluated. We analyzed plasma HCV RNA load in 396 HCV-monoinfected and 467 HIV/HCV-coinfected patients. Median HCV RNA concentrations (interquartile range) in HCV-monoinfected patients were 5.88 (5.3-6.2) log(10)IU/mL versus 5.96 (5.6-6.5) log(10)IU/mL in HIV/HCV-coinfected individuals (p=0.033) as determined with the Cobas Amplicor Test and 6.06 (5.4-5.7) log(10)IU/mL versus 6.3 (5.5-6.9) log(10)IU/mL (p=0.026) using the Cobas TaqMan System. The plasma HCV RNA load in patients with HIV infection and undetectable plasmatic HIV RNA was similar to that observed in HCV-monoinfected individuals [6.02 (5.45-6.61) log(10)IU/mL versus 6.01 (5.36-6.59) log(10)IU/mL, respectively (p=1.0)]. In conclusion, HIV coinfection tends to be associated with higher plasma HCV RNA load, however, the magnitude of the differences is small and this effect can be counterbalanced with antiviral therapy.
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