Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

Abstract

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, prior 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 (naïve, central memory (CM), 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 naïve CD4+ (P=0.03), 33% more EM CD4+ (P=0.0002) and 37% fewer CM CD8+ (P=0.02) T-cells. Among HIV-positives we observed only one of these three relationships: higher percentage of EM CD4+ among HCV viremic women. Further, 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.

The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women

“…HCV has been reported to have an impact on T cell phenotypes in HIV-1-infected persons. 43 Although there was no significant difference in HCV serostatus between the groups, there was a significant association of HCV seropositivity with CMV IgG levels among HIV-1 viremic women.…”

Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects

“…HCV/HIV coinfection is known to be associated with lower CD4 counts and a smaller CD4-cell recovery [22,23] attributed to homeostatic alterations in CD4 subsets or thymic defects. [24–26] Our data show a significant association of lower CD4 numbers with worse fibrosis suggesting that immune failure is a strong correlate of liver fibrosis in HCV/HIV coinfected patients.…”

“…[10,29] More recent studies have reported CD8 T-cell activation is not enhanced in HCV/HIV coinfected [11,24,30] and HCV/HIV coinfected subjects have activated CD4 T cells. [11,24] An earlier study in the WIHS cohort by Kovacs et al [29] reported elevated CD8 T-cell activation in HCV/HIV coinfected subjects, wherein HIV-1 disease in most women was at an early stage: almost 50% were untreated and only 7.7% were receiving HAART. In contrast, a more recent study in WIHS cohort by Kuniholm et al [24] assessing T-cell phenotype in HIV-infected women stratified by HCV RNA did not find CD8 T-cell activation in HCV/HIV coinfected women.…”

“…[11,24] An earlier study in the WIHS cohort by Kovacs et al [29] reported elevated CD8 T-cell activation in HCV/HIV coinfected subjects, wherein HIV-1 disease in most women was at an early stage: almost 50% were untreated and only 7.7% were receiving HAART. In contrast, a more recent study in WIHS cohort by Kuniholm et al [24] assessing T-cell phenotype in HIV-infected women stratified by HCV RNA did not find CD8 T-cell activation in HCV/HIV coinfected women. A Scandinavian study by Gonzalez et al [10] showed immune activation as determined by CD38 expression in T cells to be more pronounced despite successful suppression of HIV in HCV/HIV coinfected subjects than in the appropriate monoinfected controls.…”

Progressive multifocal leukoencephalopathy secondary to hepatitis C virus infection‐related T‐cell lymphopenia

“…Chronic HCV infection has rarely been known to be associated with lymphopenia, but its immune modulatory effects have been increasingly recognised . One previous study reported CD4 + lymphopenia in 43% of 62 HCV‐related cirrhosis cases .…”