Background: Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4+ count).
Methods: We used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4+ and CD8+ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.
Results: In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4+ (P = 0.03), 33% more EM CD4+ (P = 0.0002), and 37% fewer central memory CD8+ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4+ among HCV viremic women. Furthermore, the association with EM CD4+ among HIV positives was limited to individuals with diminished immune status (total CD4+ count ≤500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4+ and Tregs. Among HIV positives with high CD4+ count, no significant associations were observed.
Conclusions: These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4+ count.
*Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY;
†Department of Medicine, Montefiore Medical Center, Bronx, NY;
‡Department of Pediatrics, University of Southern California, Los Angeles, CA;
§Department of Medicine, University of California San Francisco, San Francisco, CA;
‖Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
¶Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, IL;
#Department of Medicine, Georgetown University Medical Center, Washington, DC;
**Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY;
††Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL; and
‡‡Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, the Netherlands.
Correspondence to: Mark H. Kuniholm, PhD, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Belfer Building, Room 1308C, 1300 Morris Park Avenue, Bronx, NY 10461 (e-mail: firstname.lastname@example.org).
Funding for the current project was provided in part by Grants R01CA085178 (H.D.S.), R01A1052065 (A.A.K.), 1R01HL095140 (R.C.K.), and 1R21HL120394 (R.C.K.). M.H.K. is supported in part by the National Center for Advancing Translational Sciences (NCATS), through CTSA Grants UL1RR025750 and KL2RR025749. Clinical data and specimens used in this study were collected by the Women's Interagency HIV Study (WIHS). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA).
The authors have no conflicts of interest to disclose.
The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).
WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (K.A.), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen), U01-AI-034993; Metropolitan Washington WIHS (M.A.Y.), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I—WIHS IV).
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Received April 02, 2014
Accepted July 09, 2014