Overview

This trial is active, not recruiting.

Conditions acquired immune deficiency syndrome, hepatitis, viral, non-a, non-b, parenterally-transmitted, hiv infections
Sponsor UPECLIN HC FM Botucatu Unesp
Start date August 2007
End date January 2009
Trial size 110 participants
Trial identifier NCT00499434, upeclin/HC/FMB-Unesp-14

Summary

This study aims at correlating TNF-α, INF-γ, IL-2, IL-4, IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIV/HCV coinfection. This population will be divided into three groups (G1: with no HAART; G2: with detected HIV viral load (HIV VL); G3: with undetected HIV VL), which will be then compared to two control groups with monoinfection by HIV or by HCV, in addition to a third control group comprising normal blood donors.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective

Primary Outcomes

Measure
This study aims at correlating TNF-α, INF-γ, IL-2, IL-4, IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIV/HCV coinfection
time frame: Two years

Secondary Outcomes

Measure
This study aims at correlating TNF-α, INF-γ, IL-2, IL-4, IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with CD4 and HIV viremia values in individuals with HIV/HCV coinfection
time frame: Two years

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

Inclusion Criteria: - Diagnosis of HIV infection or aids - Diagnosis of chronic hepatitis C Exclusion Criteria: - Other hepatic diseases

Additional Information

Official title Correlation Between Values of Serum Cytokines and of Those Dosed by mRNA Expression Through the Use of Real-time PCR and Hepatic Histology in Patients Infected by HIV-1 and the Hepatitis-C Virus
Principal investigator Alexandre N Barbosa, MD, MSc
Description Infection by the hepatitis-C virus (HCV) in people living with HIV/AIDS (PLHA) has progressively gained distinction since the survival increase generated by the use of highly active antiretroviral therapy (HAART) has enabled the presentation of complications from HCV chronic infection. There are approximately 10 million coinfected individuals, that is, 25% of the total PLHA as both viruses share transmission routes. HCV infection can be regarded as an opportunistic disease in this population once there is the acceleration of its natural history represented by the HCV high viral load, early hepatic fibrosis and greater occurrence of steatosis, cirrhosis and hepatocellular carcinoma, leading to greater morbid-mortality by terminal hepatic disease. The scenario is not also favorable as regards HCV treatment, since the response rate in coinfected individuals is significantly lower than in mono-infected HCV patients. The complex relationship between immune response and HCV determines the velocity and the distinct outcomes found. The major determinant for the development of cirrhosis and hepatic insufficiency is the accumulation of fibrosis and inflammatory activity closely related to collagen synthesis by fibroblasts and hepatocyte-apoptosis induction related to TGF-β production. In individuals with more severe hepatic lesion, there is the prevalence of expression of the Th-2 profile in the peripheral blood, which is characterized by high levels of IL-4 and IL-10, whereas, in the hepatic tissue, a larger expression of cytokines of the Th-1 profile, such as IL-2 and INF-γ, is observed. This phenomenon is known as "compartmentalization" of the immune response. If the immunopathogenic dynamics is already complex in HCV mono-infected individuals, in the HIV/HCV coinfection condition, few studies specifically approach the topic, without, however, evaluating the correlation between specific T-cell response and hepatic-lesion staging. In HIV mono-infected patients without antiretroviral treatment and with disease progression, the prevalence of the Th-0/Th-2 profile is observed, which is particularly influenced by IL-10 increase. Even in individuals treated by HAART, there is no recovery of the capacity to express the Th-1 profile, and most of such patients show the mature Th-0 profile and low IL-2 levels. HCV viral load in PLHA is higher in both the plasma and the hepatic tissue, and the replication of HCV in macrophages, CD4 and CD8 T lymphocytes as well as in lymphnodes is also observed in such condition. TGF-β is particularly high in this coinfection, thus justifying the onset of faster fibrosis. The reduction of CD8 T lymphocyte response to IFN-γ also occurs, which favors the persistence of infection and prevents specific T-cell response. As regards HIV treatment, there is evidence that coinfected patients non-treated by HAART tend to present a Th-2 profile more often than treated individuals, without, however, significant differences in TGF-β levels. Due to the lack of studies correlating the production tendencies of both pro-inflammatory and fibrogenesis-inducing cytokines with histopathological findings from hepatic biopsy in coinfected individuals, investigations are necessary in order establish parameters that will allow the prediction of a better or worse prognosis and also more accurately indicate the performance of hepatic biopsy. This study aims at correlating TNF-α, INF-γ, IL-2, IL-4, IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIV/HCV coinfection. This population will be divided into three groups (G1: with no HAART; G2: with detected HIV viral load (HIV VL); G3: with undetected HIV VL), which will be then compared to two control groups with monoinfection by HIV or by HCV, in addition to a third control group comprising normal blood donors.
Trial information was received from ClinicalTrials.gov and was last updated in December 2009.
Information provided to ClinicalTrials.gov by UPECLIN HC FM Botucatu Unesp.