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Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections.

ABSTRACT: BACKGROUND:HIV and hepatitis C virus (HCV) infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood. METHODS:Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users. RESULTS:Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV monoinfected, and 27% were HCV/HIV coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection [? = 0.191, 95% confidence interval (CI): 0.043 to 0.339] and HCV/HIV coinfection (? = 0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (? = -0.523, 95% CI: -0.275 to -0.789) and HCV/HIV coinfection (? = -0.554 95% CI: -0.260 to -0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (P = 0.003) and CRP (P < 0.001); increasing comorbidity (P < 0.001) and older age (P = 0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (P = 0.021). CONCLUSION:HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.

SUBMITTER: Salter ML

PROVIDER: S-EPMC3848037 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections.

Salter Megan L ML Lau Bryan B Mehta Shruti H SH Go Vivian F VF Leng Sean S Kirk Gregory D GD

Journal of acquired immune deficiency syndromes (1999) 20131201 5

<h4>Background</h4>HIV and hepatitis C virus (HCV) infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood.<h4>Methods</h4>Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users.<h4>Results</h4>Mean age w ...[more]

PMID: 23978997

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Project description:Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.

Project description:Chronic hepatitis negatively affects persons living with HIV. While varying in their transmission efficiency, HIV, HBV, and HCV have shared routes of transmission. Available data suggest widely variable rates of HBV and HCV infections in HIV-infected populations across sub-Saharan Africa. With prolonged survival rates due to increased accessibility to antiretroviral drugs, HBV and HCV have the potential to complicate the prognosis of HIV co-infected patients by contributing significantly to continued morbidity and mortality. The study sought to determine the seroprevalence of HIV/HBV and HIV/HCV co-infections among HIV patients on antiretroviral therapy and to evaluate the effect of HIV/HBV and HIV/HCV co-infections on the immunologic and virologic responses of patients. A cross-sectional study in which samples were taken from 500 people living with HIV and attending ART clinic at the Fevers unit of the Korle Bu Teaching Hospital and tested for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C virus antibody (HCV). CD4 cell counts and HIV-1 RNA levels were estimated as well. Data generated were analysed using IBM SPSS version 22. The seroprevalence of HIV/HBV and HIV/HCV co-infections among people living with HIV was 8.4% and 0.2% respectively. HIV/HBV coinfection included 15/42 (35.7%) males and 27/42 (64.3%) females out of which the majority (97.6%) were in the 21-60 years old bracket. HIV/HBV and HIV/HCV co-infections have varied effects on the immunological and virological response of HIV patients on ART. The mean CD cell count was 361.0 ± 284.0 in HIV/HBV co-infected patients and 473.8 ± 326.7 in HIV mono-infected patients. The mean HIV-1 RNA level was not significantly different (X2 [df] = .057 [1]; P = .811) among HIV/HBV co-infected patients (Log102.9±2.0 copies/mL), compared to that of HIV mono-infected patients (Log102.8±2.1 copies/mL) although HIV mono-infected patients had lower viral load levels. One-third (14/42) of HIV/HBV co-infected patients had virologic failure and the only HIV/HCV co-infected patient showed viral suppression. 336/500 (67.2%) patients had HIV-1 viral suppression (females [66.1%]; males [33.9%]) while 164/500 (32.8%) had virologic failure (females [67.7%]; males [32.3%]). The mean CD4 count of patients with viral suppression and patients with virologic failure was 541.2 cells/μL (95% CI 508.5-573.8) and 309.9 cell/μL (95% CI 261.9-357.9) respectively.The study concludes that, HIV/HBV and HIV/HCV coinfections do not significantly affect the immunologic and virologic responses of patients who have initiated highly active antiretroviral therapy, and treatment outcomes were better in females than in males. There was no HBV/HCV co-infection among patients.

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Dataset Information

Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections.

Publications

Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections.

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