Relationships between cellular immune responses and treatment outcomes with interferon and ribavirin in HIV/hepatitis C virus co-infection.

TitleRelationships between cellular immune responses and treatment outcomes with interferon and ribavirin in HIV/hepatitis C virus co-infection.
Publication TypeJournal Article
Year of Publication2006
AuthorsGraham CS, Wells A, Liu T, Sherman KE, Peters M, Chung RT, Bhan AK, Andersen J, Koziel MJames
Corporate AuthorsACTG 5071 Study Team
Date Published2006 Feb 14
KeywordsAdolescent, Adult, Aged, Antiviral Agents, Disease-Free Survival, Hepatitis C, Chronic, HIV Infections, Humans, Immunity, Cellular, Interferon-alpha, Middle Aged, Polyethylene Glycols, Recombinant Proteins, Ribavirin, Treatment Outcome

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.

DESIGN: 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.

Alternate JournalAIDS
PubMed ID16439867
PubMed Central IDPMC4060610
Grant ListAI 38858 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
DA14495-01 / DA / NIDA NIH HHS / United States
R01 AI050752 / AI / NIAID NIH HHS / United States