Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study

Seema N. Desai, Jennifer L. Dodge, Alan L. Landay, Marshall J. Glesby, Patricia S. Latham, Maria C. Villacres, Audrey L. French, Stephen J Gange, Ruth M. Greenblatt, Marion G. Peters

Research output: Contribution to journalArticle

Abstract

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear. In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI). We found liver fibrosis (APRI) was 50% lower in Elites and ARTc compared to ARTuc. Higher liver fibrosis was associated with significantly low CD4+ T cell counts (P < 0.001, coefficient r = -0.463). Immune activation varied by HIV phenotype but was not modified by HCV viremia. HCV viremia was associated with elevated CD8 T-cell Caspase-3 in Elites, ARTuc, and HIV- except ARTc. CD8 T-cell Caspase-3 levels were significantly higher in HCV RNA+ Elites (P = 0.04) and ARTuc (P = 0.001) and HIV- groups (P = 0.02) than ARTc. Importantly, ARTuc HCV RNA+ had significantly higher CD4 T-cell interleukin-17 levels than ARTuc HCV RNA- (P = 0.005). HIV control was associated with lower liver fibrosis in HCV/HIV co-infected women. HCV viremia is associated with an inflammatory CD4 TH-17 phenotype in absence of HIV control and higher frequency of pro-apoptosis CD8 T-cells critical to avert progression of HIV and HCV disease that is attenuated in ART controllers. Elite controllers with HCV viremia are more prone to CD8 T-cell apoptosis than ART controllers, which could have negative consequences over time, highlighting the importance of ART control in HCV/HIV coinfected individuals.

Original languageEnglish (US)
Article numbere20104
JournalMedicine
Volume95
Issue number33
DOIs
StatePublished - Aug 1 2016

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Keywords

  • antiretroviral therapy
  • apoptosis
  • elite controllers
  • HCV/HIV
  • hepatic fibrosis
  • immune activation
  • TH-17

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Desai, S. N., Dodge, J. L., Landay, A. L., Glesby, M. J., Latham, P. S., Villacres, M. C., French, A. L., Gange, S. J., Greenblatt, R. M., & Peters, M. G. (2016). Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study. Medicine, 95(33), [e20104]. https://doi.org/10.1097/MD.0000000000004483