AEGiS-13IAC: Immunological responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Immunological responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA526)

Valdez H, Anthony D, Farukhi F, Patki A, Salkowitz J, Heeger P, Peterson D, Asaad R, Lederman M
H. Valdez, Case Western Reserve University, 2061 Cornell, Rm 301B, Cleveland, OH 44106, United States, Tel.: +1 216 844-2057, Fax: +1 216 844-5523, E-mail: valdez.hernan@clevelandactu.org

BACKGROUND: 85% of HCV-infected patients are chronically viremic and a variable proportion develops cirrhosis and hepatocellular carcinoma. Vigorous HCV-specific CD4 responses are associated with clearance of HCV viremia, but these are absent or of low magnitude in most patients with chronic HCV infection. HIV-HCV coinfected patients have higher HCV viral loads (VL) and progress faster to cirrhosis and hepatocellular carcinoma than HCV-infected subjects. We examined immune phenotype and function in HCV(+) subjects to better characterize immune function in HCV infection in the presence and absence of HIV infection.

METHODS: Uninfected = Un (9), HCV-infected = HCV(+) (9), HCV-HIV infected = HIV/HCV (10), HCV-HIV infected on HIV treatment = HIV/HCV-Tx (9), and untreated HIV-infected, HCV-uninfected = HIV(+) (10) patients had blood drawn for flow cytometry, lymphocyte proliferation and ELISPOT assays. Entry criteria: no cirrhosis, >300 CD4 (HIV), no recent treatment with IFN or Hepatitis B coinfection.

RESULTS: Patients were well matched for age and gender. HCV infection tended to cause an increase in the percentage of activated CD8 cells (U = 2%, HCV(+) = 6%, p = 0.1). Proliferative responses to non-HCV antigens were comparable in HCV(+) and U subjects. A greater proportion of HCV(+) had a stimulation index (SI) >3 to NS3 compared to HIV/HCV and HIV/HCV-Tx (67%, 0%, 11%, p>0.006) and the log SI to NS3 was significantly higher (p>0.04, p>0.009) in HCV(+) (median, IQR 0.6,0.5) than in HIV/HCV (0.3,0.5) or HIV/HCV-Tx (0,0.4). Among HCV-infected patients HCV-VL correlated directly with ALT (r = 0.52, p>0.01) and inversely with the number of CD4+ lymphocytes (r = -0.55,p>0.008) and proliferation to NS3 (r = -0.55,p>0.008).

CONCLUSIONS: Lymphocytes of HCV-infected patients fail to respond to HCV antigens while responses to other antigens are preserved. Infection with HIVpotentiates this deficiency. Poor CD4+ T cell responses to HCV may determine the failure to control HCV propagation.

Keywords: AEGIS, Hepatitis C Antigens, Hepatitis C, Hepacivirus, HIV, HIV Infections, Viral Load, CD4-Positive T-Lymphocytes, Viremia, HIV Seropositivity, Hepatitis C Antibodies, HIV Long-Term Survivors, CD8-Positive T-Lymphocytes, Antigens, CD4, Anti-HIV Agents, Case-Control Studies, Human, immunology
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