Relationships between cellular immune responses and treatment outcomes with interferon and ribavirin in HIV/hepatitis C virus co-infection.
OBJECTIVE
To test the hypothesis that hepatitis C virus (HCV)-specific interferon (IFN)gamma immune responses are correlated with HCV virological response following treatment in subjects with HIV-1 and HCV co-infection.


METHODS
Immune responses were studied in a treatment trial comparing standard interferon alfa (IFN) to pegylated interferon alfa (PEG-IFN), each with ribavirin (R).


METHODS
Using HCV antigens core, NS3 and NS5, and Candida, enzyme-linked immunosorbent spots on peripheral blood mononuclear cells measured IFNgamma and interleukin (IL)-10 production. Immunologic, virologic and clinical variables were modeled using recursive partitioning (CART) to identify factors associated with HCV virological response at week 24 (VR) and week 72 (SVR) in 108 patients.


RESULTS
There were no significant differences in baseline IFNgamma immune responses and higher IL-10 to NS3 in subjects with VR versus non-responders. Subjects who had significant decreases in IL-10 responses at week 24 compared to baseline for NS3, NS5, or summed HCV responses were more likely to be VR. Using baseline immunological responses and clinical data in CART models, patients who were randomized to PEG-IFN/R and had high IL-10 responses to summed HCV proteins were more likely to be VR (73%), whereas those on IFN/R who had low IFNgamma responses to Candida were less likely to be VR (5%). The main correlate of SVR for genotype-1 subjects was maintenance of HCV-specific IFNgamma responses from baseline to week 72.


CONCLUSIONS
In this cohort of subjects with HIV and HCV, a decrease in HCV-specific IL-10 responses and maintenance of IFNgamma responses during treatment with IFN were associated with week 24 or 72 virological response.
Graham
Camilla S
CS
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA. cgraham@bidmc.harvard.edu
Wells
Annalee
A
Liu
Tun
T
Sherman
Kenneth E
KE
Peters
Marion
M
Chung
Raymond T
RT
Bhan
Atul K
AK
Andersen
Janet
J
Koziel
Margaret James
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a