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Published on: July 16, 2012
Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy
Janine Rohrbach1, Nicola Robinson, Gillian Harcourt
1Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland.
Insights
Long-term combination antiretroviral therapy (cART) boosts Hepatitis C virus (HCV)-specific T cell responses in HIV-coinfected individuals. This treatment also leads to a modest reduction in HCV RNA levels, improving immune control.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) infection significantly impacts morbidity in individuals with HIV coinfection.
- HIV coinfection is linked to weaker HCV-specific immune responses and higher viral loads.
Purpose of the Study:
- To determine if long-term combination antiretroviral therapy (cART) can restore HCV-specific T cell responses.
- To assess if cART improves the control of HCV replication in coinfected individuals.
Main Methods:
- Longitudinal evaluation of T cell responses using interferon-gamma-ELISpot assays against HCV core peptides in 80 HIV/HCV coinfected individuals.
- Assessment of HCV RNA levels via real-time PCR in 114 individuals.
Main Results:
- Detectable T cell responses to HCV core peptides increased from 19% before cART to 45-49% after 33-70 months (p=0.001).
- HCV-specific immune responses improved in both chronic (+31%) and spontaneously cleared (+30%) HCV infections.
- Median HCV RNA levels showed a slight decrease (-0.3 log10 IU/ml, p=0.02) during long-term cART.
Conclusions:
- Effective cART is associated with enhanced cellular immune responses to HCV core peptides.
- Long-term cART leads to a modest reduction in HCV RNA levels.
- Findings support the favorable clinical impact of cART on hepatitis C progression and early treatment initiation in coinfected patients.
Background:
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.
Aims:
To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.
Methods:
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.
Results:
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).
Conclusions:
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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