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

Gut doi:10.1136/gut.2009.205971

Paper

Janine Rohrbach 1, Nicola Robinson 2, Gillian Harcourt 2, Emma Hammond 3, Silvana Gaudieri 3,4, Meri Gorgievski 5, Amalio Telenti 6, Olivia Keiser 7, Huldrych F Günthard 8, Bernhard Hirschel 9, Matthias Hoffmann 10, Enos Bernasconi  11, Manuel Battegay 12, Hansjakob Furrer 1, Paul Klenerman 2, Andri Rauch 1,3, the Swiss HIV Cohort Study

1 Division of Infectious Diseases, University Hospital Berne and University of Berne, Switzerland
2 Nuffield Department of Clinical Medicine, Oxford University, UK
3 Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia
4 Centre for Forensic Sciences and School of Anatomy and Human Biology, University of Western Australia, Perth, Australia
5 Institute for Infectious Diseases, University of Berne, Switzerland
6 Institute of Microbiology, University Hospital Centre and University of Lausanne, Switzerland
7 Institute of Social and Preventive Medicine, University of Berne, Switzerland
8 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland
9 Department of Infectious Diseases, Geneva University Hospital, Switzerland
10 Division of Infectious Diseases, Kantonsspital St Gallen, Switzerland
11 Division of Infectious Diseases, Ospedale Regionale di Lugano, Switzerland
12 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Switzerland

Correspondence to
Andri Rauch, Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland; andri.rauch@insel.ch

Revised 31 March 2010
Accepted 13 April 2010
Published Online First 26 July 2010

Abstract

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-γ-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 log10 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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