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Characterization of CD4+ T-Cell Immune Activation and Interleukin 10 Levels Among HIV, Hepatitis C Virus, and HIV/HCV-Coinfected Patients

Hodowanec, Aimee C. MD*,†; Brady, Kirsten E.; Gao, Weihua PhD§; Kincaid, Stacey L.*; Plants, Jill; Bahk, Mieoak*; Landay, Alan L. PhD; Huhn, Gregory D. MD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1st, 2013 - Volume 64 - Issue 3 - p 232–240
doi: 10.1097/QAI.0b013e31829c6de0
Basic and Translational Science

Background: HIV/hepatitis C virus (HCV)–coinfected patients have accelerated liver disease compared with HCV monoinfection. In HIV-positive patients with viral suppression, data comparing inflammatory cytokines and immune activation between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV-seropositive patients with cleared HCV are limited.

Methods: Fifty-nine age- and sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver fibrosis was assessed in each subject using transient elastography. Cells were collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow cytometry and plasma for luminex–multiplex cytokine assays.

Results: CD38+HLA-DR+ expression on CD4+ T cells was significantly increased in HIV/HCV coinfection with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4+ total HLA-DR+ expression was significantly increased in HIV/HCV coinfection with CHC (43%) versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared HCV (38%) (P = 0.046). Total CD4+CD38+ and CD4+CD38+HLA-DR expression was significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P = 0.0002). In multivariate analysis, severe fibrosis was associated with lower expression of CD4+CD38+HLA-DR+ and CD4+ total CD38+ than mild-moderate fibrosis (P = 0.03 and 0.03, respectively).

Conclusions: CD4 immune activation with HLA-DR+ expression in HIV/HCV coinfection with well-controlled HIV may arise from chronic HCV viremia. Conversely, CD4+CD38+ expression may be driven by underlying HIV infection. CD4 immune activation was unexpectedly found to be associated with decreased liver fibrosis.

*Ruth M. Rothstein CORE Center, John H. Stroger Jr. Hospital of Cook County, Chicago, IL;

Section of Infectious Diseases, Rush University Medical Center, Chicago, IL;

Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL; and

§Center for Clinical and Translational Sciences, University of Illinois at Chicago, Chicago, IL.

Correspondence to: Aimee C. Hodowanec, MD, Section of Infectious Diseases, Rush University Medical Center, 600 S. Paulina St, Suite 140-143, Chicago, IL 60612 (e-mail:

The study was funded by Merck's Clinical Investigators-Initiated Studies Program.

Presented at XIX International AIDS Conference, July 22–27, 2012, Washington, DC.

G.H. has received honoraria from Gilead, Tibotec, Merck, Novartis, Sanofi, GSK, and Genentech and has received grants from Merck, Tibotec, Gilead, and GSK. The remaining authors have no funding or conflicts of interest to disclose.

Received February 06, 2013

Accepted May 17, 2013

© 2013 by Lippincott Williams & Wilkins