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

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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.

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Authors and Affiliations

  1. Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard Street, Baltimore, MD, 21201, USA

    Benjamin Emmanuel, Kristen A. Stafford, Bhawna Poonia & Shyam Kottilil

  2. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA

    Samer S. El-Kamary, Laurence S. Magder & Kristen A. Stafford

  3. Department of Epidemiology and Prevention, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, USA

    Man E. Charurat

  4. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA

    Cheryl Chairez, Mary McLaughlin & Colleen Hadigan

  5. Clinical Center, National Institutes of Health, Bethesda, USA

    Henry Masur

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  1. Benjamin Emmanuel
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Corresponding author

Correspondence to Shyam Kottilil.

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Conflict of interest

B. Emmanuel, S.S. El-Kamary, L.S. Magder, K.A. Stafford, M.E. Charurat, B. Poonia, C. Chairez, M. McLaughlin, C. Hadigan, H. Masur, and S. Kottilil have no conflict of interest.

Ethical standard

The primary study was approved by the NIAID IRB and conducted in compliance with the Good Clinical Practice guidelines, the Declaration of Helsinki, and regulatory requirements.

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All patients provided written informed consent and all protocols were approved by the NIH/NIAID Institutional Review Board.

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Emmanuel, B., El-Kamary, S.S., Magder, L.S. et al. Immunological recovery in T-cell activation after sustained virologic response among HIV positive and HIV negative chronic Hepatitis C patients. Hepatol Int 13, 270–276 (2019). https://doi.org/10.1007/s12072-019-09941-8

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  • DOI: https://doi.org/10.1007/s12072-019-09941-8

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