Detail Research Data


Data Doctoral/PhD
Research Title Immunological Profile and Predictor of HCV Immune Restoration Disease among HIV and HCV coinfected Patients Starting HAART
Kaji Etik Pass Number 4007
Kaji Etik Pass Date 05 November 2007
Focus Infectious Diseases
Principal Investigator Evy Yunihastuti
Promotor Prof.Dr.dr. Heru Sundaru SpPD(K)
Co Promotor SpPD, PhD, KGEH L.A.Lesmana Prof, Dr
Co Promotor Patricia price
Departement Internal Medicine
Category Clinic
Research Date 05 November 2007
Research Object Manusia
Fund Source Mandiri
Level Penelitian Doctoral/PhD
Abstract

Introduction

Some of HIV and HCV coinfected patients could experience an i mmunopatho logical phenomenon after commencing highly active antiretroviral therapy (HAART) that was known as HCV immune restoration disease (HCV IRD). Little is known of the pathogenesis and predictor the HCV immune restoration disease in HIV/HCV coinfected individuals. This study was designed to describe the clinical characteristics and incidence of HCV IRD, to analyze immunological profile of HCV IRD, to assess HCV RNA levels and to identify predictors of HCV IRD.

Methods

This was a 24 weeks cohort study of 50 treatment-naive HIV/HCV-coinfected individuals who were beginning HAART in HIV Clinic Ciptomangunkusumo Hospital, Jakarta. HCV IRD was defined as increase of alanine aminotransferase (ALT) level to 5 times upper normal limit or 3 times baseline level and 1 log decrease in HIV-RNA levels after commencing HAART. Plasma levels of HCV-specific antibody, CXCLIO, sCD26, sCD30, IL-18, TGF-(31 and HCV-RNA were quantified before treatment, at week 4, 8, 12, 24 and any HCV-IRD event. Linear mixed effect models with random intercept and slope were used to identify differences in levels of plasma markers and HCV-RNA between patients who experienced HCV IRD and patients who did not experience this IRD. Logistic regression was used to define predictors of HCV IRD.

Results

Nine patients experienced HCV IRD during 24 weeks after commencing HAART (the incidence was 9.2 per 100 person week). Clinical manifestations accompanying elevation of ALT levels were nausea and vomitus that resolved without changing the treatment. Soluble CD30 (a marker of T cell activation) shown a trend of increment during HCV IRD (coefficient 39.7, p= 0.061). Markers of T cell activation (sCD26) and immune recruitment to the liver (CXCL10) also increased in some HCV IRD cases. Total anti-HCV antibody (assessed with a commercial assay based on core, NS3 and NS5 antigens) was consistently lower in patients who developed HCV IRD (p<0.001), but antibody assessed in house using HCV core antigen did not show this pattern. There were no significant changes in HCV-RNA during HCV-IRD. Low baseline levels of total anti-HCV antibody and absolute CD4+ T-cell counts were the best predictor of HCV IRD (area under ROC curve = 0.8591, sensitivity 88.89% and specificity 82.93%). There was a negative correlation between baseline HCV-RNA and total anti-HCV antibody in all patients.

Conclusion

High levels of baseline total anti-HCV antibody protect against HCV IRD. As these correlated with HCV RNA levels, the likely mechanism is a reduction in HCV antigen load.T-cell dependent mechanisme are implicated in HCV IRD, since many patients exhibited rises in Scd 26, sCD30 and CXCL10

Keywords

Hepatitis C immune restoration disease, immunological profile, predictor