Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy
- Janine Rohrbach1,
- Nicola Robinson2,
- Gillian Harcourt2,
- Emma Hammond3,
- Silvana Gaudieri3,4,
- Meri Gorgievski5,
- Amalio Telenti6,
- Olivia Keiser7,
- Huldrych F Günthard8,
- Bernhard Hirschel9,
- Matthias Hoffmann10,
- Enos Bernasconi11,
- Manuel Battegay12,
- Hansjakob Furrer1,
- Paul Klenerman2,
- Andri Rauch1,3,
- the Swiss HIV Cohort Study
- 1Division of Infectious Diseases, University Hospital Berne and University of Berne, Switzerland
- 2Nuffield Department of Clinical Medicine, Oxford University, UK
- 3Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia
- 4Centre for Forensic Sciences and School of Anatomy and Human Biology, University of Western Australia, Perth, Australia
- 5Institute for Infectious Diseases, University of Berne, Switzerland
- 6Institute of Microbiology, University Hospital Centre and University of Lausanne, Switzerland
- 7Institute of Social and Preventive Medicine, University of Berne, Switzerland
- 8Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland
- 9Department of Infectious Diseases, Geneva University Hospital, Switzerland
- 10Division of Infectious Diseases, Kantonsspital St Gallen, Switzerland
- 11Division of Infectious Diseases, Ospedale Regionale di Lugano, Switzerland
- 12Division 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;
- Revised 31 March 2010
- Accepted 13 April 2010
- Published Online First 26 July 2010
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.
See commentary, p 1167
The members of the Swiss HIV Cohort Study are: M Battegay, E Bernasconi, J Böni, HC Bucher, Ph Bürgisser, A Calmy, S Cattacin, M Cavassini, R Dubs, M Egger, L Elzi, P Erb, M Fischer, M Flepp, A Fontana, P Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, CH-1011, Lausanne), H Furrer (Chairman of the Clinical and Laboratory Committee), C Fux, M Gorgievski, H Günthard (Chairman of the Scientific Board), H Hirsch, B Hirschel, I Hösli, Ch Kahlert, L Kaiser, U Karrer, C Kind, Th Klimkait, B Ledergerber, G Martinetti, B Martinez, N Müller, D Nadal, M Opravil, F Paccaud, G Pantaleo, A Rauch, S Regenass, M Rickenbach (Head of Data Center), C Rudin (Chairman of the Mother & Child Substudy), P Schmid, D Schultze, J Schüpbach, R Speck, P Taffé, P Tarr, A Telenti, A Trkola, P Vernazza, R Weber, S Yerly.
Funding This study has been financed in the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (SNF grants #3345-062041 and #324730-116862), the Wellcome Trust and the James Martin School for 21st Century Oxford, the NIHR Biomedical Research Centre Program Oxford and the National Health and Medical Research Council Program, Western Australia. The study sponsors had no role in the study design, data collection, analysis, interpretation of data and writing of this manuscript.
Competing interests None.
Ethics approval This study was performed in the framework of the Swiss HIV Cohort Study (www.shcs.ch). Written informed consent, including for genetic testing, was mandatory for inclusion, and the study was approved by all local ethical committees.
Provenance and peer review Not commissioned; externally peer reviewed.