Immunological recovery in T-cell activation after sustained virologic response among HIV positive and HIV negative chronic Hepatitis C patients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-05

AUTHORS

Benjamin Emmanuel, Samer S. El-Kamary, Laurence S. Magder, Kristen A. Stafford, Man E. Charurat, Bhawna Poonia, Cheryl Chairez, Mary McLaughlin, Colleen Hadigan, Henry Masur, Shyam Kottilil

ABSTRACT

BACKGROUND: Rapid decreases in activated CD4+ and CD8+ (HLA-DR + and CD38+ co-expressed) T-lymphocytes have been described within 1-2 weeks of initiating direct-acting antiviral (DAA) therapy among chronic Hepatitis C (CHC) patients. However, it is not known whether these changes are maintained past sustained virologic response (SVR), particularly in those who are HIV/HCV-coinfected. METHODS: We investigated the changes in immune parameters of T-lymphocytes from pre-DAA therapy to post-SVR among HIV negative and HIV positive patients with CHC. Repeated measurements of activated CD4+ and CD8+ T cells were analyzed by flow cytometry at pre-DAA therapy, DAA therapy, end of treatment, SVR, and post-SVR. A general linear model for repeated measurements was used to estimate the mean outcome at each timepoint and change between timepoints. RESULTS: HCV-monoinfected (n = 161) and HIV/HCV-coinfected (n = 59) patients who achieved SVR with DAA therapy were predominately middle aged, male, black, and non-cirrhotic. At pre-DAA therapy, HCV-monoinfected patients had significantly higher CD4+ T cells and CD4+:CD8+ T-cell ratio, while significantly lower CD8+ and activated CD4+ and CD8+ T cells compared to HIV/HCV-coinfected patients (p < 0.0001). HCV-monoinfected and HIV/HCV-coinfected patients had a significant mean decrease from pre-DAA therapy to post-SVR year 1 for activated CD4+ (HCV-monoinfected: 4.8-3.9%, p < 0.0001; HIV/HCV-coinfected: 6.6-4.5%, p < 0.0001) and activated CD8+ T cells (HCV-monoinfected V: 13.8-11.8%, p = 0.0002; HIV/HCV-coinfected: 18.0-12.4%, p < 0.0001). CONCLUSION: This longitudinal study showed CHC patients treated with DAA therapy had continued decrease of T-lymphocytes from start of DAA therapy to after achievement of SVR suggesting improvement as HCV clearance normalizes activated T-cell phenotype. More... »

PAGES

1-7

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12072-019-09941-8

DOI

http://dx.doi.org/10.1007/s12072-019-09941-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112541057

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30835046


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31 schema:description BACKGROUND: Rapid decreases in activated CD4+ and CD8+ (HLA-DR + and CD38+ co-expressed) T-lymphocytes have been described within 1-2 weeks of initiating direct-acting antiviral (DAA) therapy among chronic Hepatitis C (CHC) patients. However, it is not known whether these changes are maintained past sustained virologic response (SVR), particularly in those who are HIV/HCV-coinfected. METHODS: We investigated the changes in immune parameters of T-lymphocytes from pre-DAA therapy to post-SVR among HIV negative and HIV positive patients with CHC. Repeated measurements of activated CD4+ and CD8+ T cells were analyzed by flow cytometry at pre-DAA therapy, DAA therapy, end of treatment, SVR, and post-SVR. A general linear model for repeated measurements was used to estimate the mean outcome at each timepoint and change between timepoints. RESULTS: HCV-monoinfected (n = 161) and HIV/HCV-coinfected (n = 59) patients who achieved SVR with DAA therapy were predominately middle aged, male, black, and non-cirrhotic. At pre-DAA therapy, HCV-monoinfected patients had significantly higher CD4+ T cells and CD4+:CD8+ T-cell ratio, while significantly lower CD8+ and activated CD4+ and CD8+ T cells compared to HIV/HCV-coinfected patients (p < 0.0001). HCV-monoinfected and HIV/HCV-coinfected patients had a significant mean decrease from pre-DAA therapy to post-SVR year 1 for activated CD4+ (HCV-monoinfected: 4.8-3.9%, p < 0.0001; HIV/HCV-coinfected: 6.6-4.5%, p < 0.0001) and activated CD8+ T cells (HCV-monoinfected V: 13.8-11.8%, p = 0.0002; HIV/HCV-coinfected: 18.0-12.4%, p < 0.0001). CONCLUSION: This longitudinal study showed CHC patients treated with DAA therapy had continued decrease of T-lymphocytes from start of DAA therapy to after achievement of SVR suggesting improvement as HCV clearance normalizes activated T-cell phenotype.
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