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Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection

Graham, Camilla Sa; Wells, Annaleea; Liu, Tunb; Sherman, Kenneth Ec; Peters, Mariond; Chung, Raymond Te; Bhan, Atul Ke; Andersen, Janetb; Koziel, Margaret Jamesa; for the ACTG 5071 Study Team

Basic Science

Objective: To test the hypothesis that antigen-specific interferon (IFN)γ responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV).

Design: Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy.

Methods: We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNγ and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning.

Results: There were significant negative correlations between inflammatory scores and IFNγ production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNγ production in response to NS5 and summed HCV proteins. Higher IFNγ production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNγ responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNγ response to Candida.

Conclusions: In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNγ responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.

From the aBeth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

bHarvard School of Public Health, Boston, Massachusetts, USA

cUniversity of Cincinnati, Cincinnati, Ohio, USA

dUniversity of California San Francisco, San Francisco, California, USA

eMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Received 5 November, 2004

Revised 28 December, 2004

Accepted 12 January, 2005

Correspondence to C. S. Graham, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Room 221, 4 Blackfan Circle, Boston, MA 02115, USA. Tel: +1 617 667 0040; fax: +1 617 975 5235; e-mail:

Presented in part at the Tenth Conference on Retroviruses and Opportunistic Infections. Boston, February 2003 [abstract 839].

© 2005 Lippincott Williams & Wilkins, Inc.