Dominant enrichment of phenotypically activated CD38⁺HLA-DR⁺CD8⁺T cells, rather than CD38⁺HLA-DR⁺CD4⁺T cells, in HIV/HCV coinfected patients on antiretroviral therapy

Abstract

HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc.

Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients

“…Of note, both the canonical and the univariate and multivariate analyses pointed to activation and exhaustion of effector populations of T-cells as the most important to discriminate between HIV/HCV coinfected and HIV monoinfected patients. These results are in agreement with previous studies showing a significant impact of HCV coinfection on T-cells activation [ 16 , 17 , 33 , 34 , 35 ] and/or exhaustion [ 18 , 24 ]. Similar results were found in a recent study by our group employing a cohort of patients with untreated HIV infection, suggesting that in the setting of HIV infection, HCV impacts on T-cells homeostasis independently of the level of HIV replication [ 26 ].…”