Immune Biomarker Differences and Changes Comparing HCV Mono-Infected, HIV/HCV Co-Infected, and HCV Spontaneously Cleared Patients

Abstract

BackgroundImmune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine responseMethodsFifty immune biomarkers were analyzed at baseline(BL) and HCV end of treatment follow-up(FU) time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR) and non-responders (NR) at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I errorResultsCompared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatmentConclusionsClear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and co-infected had a larger percentage of African American patients, our findings may have implications for better understanding HCV pathogenesis, treatment outcomes, and future therapeutic targets

Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co‐infected patients

“…Decreasing FGFb levels can be an indication of decreasing fibrotic activity due to IFN‐ α treatment, which has been reported previously . Although many serum biomarker levels decreased significantly as a result of IFN/RBV treatment, previous work by our group indicates that at the end of HCV treatment in those who achieve SVR still have elevated levels of many biomarkers, including inflammatory cytokines compared with those who were exposed to HCV and spontaneously cleared the infection without treatment .…”

IP-10 and MIG Are Compartmentalized at the Site of Disease during Pleural and Meningeal Tuberculosis and Are Decreased after Antituberculosis Treatment

“…To balance the risks of type 1 and type 2 errors, the Bonferroni correction was used to correct the individual alpha errors for multiple comparison, using the following significance level for all biomarker analyses: ␣ ϭ 0.05/26 ϭ 0.002. An adjusted P value of Ͻ0.002 was considered significant (22). Differences of cytokine/chemokine levels between plasmas and paired pleural fluid samples were compared using the paired t test.…”

HIV infection and immune activation

“…Although the percent of activated CD4+ and CD8+ T cells and Treg were higher in HIV-infected patients compared to healthy controls, no significant differences were observed among the groups of HIV patients [87]. In a different study, biomarkers of inflammation including INFa were found to be higher in HCV/HIV co-infected patients compared to HCV mono-infected patients but importantly, some decreased after successful sustained virologic suppression (SVR) of hepatitis C [88]. Decreases in sCD163 and sICAM were also noted 24 weeks after HCV treatment with pegylated interferon/ribavirin in another cohort of 54 patients [89].…”