High Levels of Chronic Immune Activation in the T-Cell Compartments of Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 and on Highly Active Antiretroviral Therapy Are Reverted by Alpha Interferon and Ribavirin Treatment

Abstract

Chronic immune activation is a driver of human immunodeficiency virus type 1 (HIV-1) disease progression. Here, we describe that subjects with chronic hepatitis C virus (HCV)/HIV-1 coinfection display sharply elevated immune activation as determined by CD38 expression in T cells. This occurs, despite effective antiretroviral therapy, in both CD8 and CD4 T cells and is more pronounced than in the appropriate monoinfected control groups. Interestingly, the suppression of HCV by pegylated alpha interferon and ribavirin treatment reduces activation. High HCV loads and elevated levels of chronic immune activation may contribute to the high rates of viral disease progression observed in HCV/HIV-1-coinfected patients.

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…As predicted by this hypothesis, the rate of sustained virological response (SVR) to standard anti-HCV treatment with pegylated alpha interferon (peg-IFN-␣) plus ribavirin is lower in HIV/HCV-coinfected subjects than in HCV-monoinfected patients (131,132). Although several factors have been associated with the response to anti-HCV therapy, the determinants of successful full-course peg-IFN-␣-ribavirin therapy are still poorly defined (133)(134)(135)(136)(137).…”

Current and future challenges in HCV: insights from an Italian experts panel

“…Thus, treatment of HCV infection could be followed by a reduction of inflammation that may be considered as an important strategy for reducing HIV viral replication and slowing disease progression. The combination IFN-α plus ribavirin has been associated with a significant reduction in markers of both T cell activation [99] and endothelial dysfunction [100] in HIV-HCV co-infected patients receiving antiretroviral therapy.…”

Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

“…Markers of CIA apart from T cells, are also expressed in a plethora of other immune cells such as monocytes, DCs, and natural killer (NK) cells [44] . Elevated immune activation of T cell appears to be one of the potent predictors of HIV disease progression [45,46] as highly sustained immune activation may contribute to rapid disease progression by impairing the ability of the immune system to respond to antigens [47] , suggesting that CIA could be a key player in HIV pathogenesis and indirectly predicts progression to non-AIDS related morbidity and mortality [34] . Accumulating line of evidence also suggests that increased expression of CD57 and reduced levels of CD127 in patients with CIA highly correlated with T-cell dysfunction and senescence [26,27,48,49] supporting the notion of potential association between CIA and immunosenescence, especially in T cells.…”

“…While it is increasingly becoming clear that persistent HIV disease facilitates the onset of CIA and consequently to premature senescence [20,24,28,45,47,50] , existing hypotheses suggest that MTB exacerbates HIV disease by enhancing viral transmission and entry into immune cell by causing alternations in signal transduction, cytokine modulation; overcoming anti-viral responses with overwhelming HIV promoting responses; and facilitating HIV amplification by rendering the formation of granuloma [51][52][53][54] . The upregulation of immunosenescence markers on T cells appears to accelerate the depletion of functional T cells, hastening a shift to terminally-differentiated T cells with altered immune functions [55] , and hence we speculate that this potentially might facilitate the onset of AIDS, and disseminated and extra-pulmonary TB infections.…”