期刊
PLOS ONE
卷 9, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0101441
关键词
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资金
- Canadian Foundation of AIDS Research (CANFAR)
- Canadian Institutes for Health Research (CIHR)
- Fonds de recherche du Quebec - Sante (FRQS)
- FRQS
- FRQS AIDS and Infectious Disease Network (Reseau FRQS SIDA-MI)
- Canadian Institutes of Health Research [CIHR MOP-79529]
- CIHR Canadian HIV Trials Network [CTN222]
Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-alpha) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-alpha was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-alpha on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-alpha therapy with different outcomes including IFN-alpha non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127(+) CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-alpha therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.
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