THPE027 - Poster Exhibition
HCV viremia affects immune phenotypes in elite controllers of HIV infection: a Women's Interagency HIV Study (WIHS)
S. Desai1, A. Landay2, M. Glesby3, B. Edlin4, P. Latham5, M. Villaacres6, A. French7, N. Amelil8, R. Greenblatt8, M. Peters9, Women Interagency HIV Study
1Rush University Medical Center, Immunology/Microbiology and Medicine, Chicago, United States, 2Rush University Medical Center, Immunology/Microbiology, Chicago, United States, 3Weill Cornell Medical College, Infectious Diseases, New York, United States, 4SUNY Downstate Medical Center, Medicine, Brooklyn, United States, 5George Washington University, Pathology, Washington, United States, 6University of Southern California, Medicine, Los Angeles, United States, 7Stroger Hospital of Cook County, CORE Center, Chicago, United States, 8University of California, Pharmacology, San Francisco, United States, 9University of California, Medicine, San Francisco, United States
Background: HCV and HIV both independently lead to immune dysregulation. We investigated the effect of HCV viremia on immune phenotypes in HIV and HCV coinfected women in the Women Interagency HIV Study (WIHS).
Methods: We evaluated immune response patterns of elite controllers (n=20), HIV controlled (HIVc n=20) and HIV uncontrolled on cART (HIVuc n=22) compared with HIV uninfected (HIV- n=18) women, all of whom were HCV Ab positive. Within groups, we compared HCV RNA positive (HCVRNA+) and negative (HCVRNA-) women, matched by age and race. We evaluated T cell activation (CD38+, HLADR+), and apoptosis markers (Caspase-3+) as well as frequency of regulatory T cells (CD4+CD25+ FoxP3+). iNK-T cell frequency and function were measured. Cytokine responses (interferon (IFN)-g, IL-2, IL-17) were evaluated in CD4 and CD8 T cells following 6h of PMA+Ionomycin stimulation using 10 color flow cytometry.
Results: Elites/HCVRNA- had a higher % of total CD8+ (mean 42±15.6 vs 30.2±7.2; p=0.037), a trend towards higher activated CD8+ HLADR+ CD38+ (median 5.8 [17.3, 0.3 max, min] vs 3.4 [8.06,3.4] p=0.10) compared to HCVRNA-HIV- though significantly lower CD8 T cell activation compared to HIVuc (p=0.001). In the presence of HCV viremia in Elites, CD8+IFN-g+ decreased and CD8+HLADR+CD38+ increased compared to Elites/HCVRNA-, although HCV viremia did not alter the frequency of T regs.
Conclusions: While women who are elite controllers have less immune activation than HIVuc, they remain immune activated compared to HIVRNA-HCV- women. HCV infection with viremia decreases CD8 T cell IFNg responsiveness in elite controllers with HIV, an effect that may be important to the regulation of viral infections in these patients.
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