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Correlation Between Cytokines and Hepatic Histology in Patients Infected by HIV-1 and the Hepatitis-C Virus

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by UPECLIN HC FM Botucatu Unesp.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
UPECLIN HC FM Botucatu Unesp
ClinicalTrials.gov Identifier:
NCT00499434
First received: July 10, 2007
Last updated: December 3, 2009
Last verified: December 2009
  Purpose

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.


Condition
Acquired Immune Deficiency Syndrome
Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by UPECLIN HC FM Botucatu Unesp:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 110
Study Start Date: August 2007
Estimated Study Completion Date: February 2010
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

SAE e Hospital Dia de Aids patients

Criteria

Inclusion Criteria:

  • Diagnosis of HIV infection or aids
  • Diagnosis of chronic hepatitis C

Exclusion Criteria:

  • Other hepatic diseases
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499434

Locations
Brazil
SAE e Hospital Dia de Aids
Botucatu, Sao Paulo, Brazil, 18618970
Sponsors and Collaborators
UPECLIN HC FM Botucatu Unesp
Investigators
Principal Investigator: Alexandre N Barbosa, MD, MSc UPECLIN HC FM Botucatu Unesp
  More Information

No publications provided

Responsible Party: Alexandre Naime Barbosa, SAE e Hospital Dia de Aids - Faculdade de Medicina de Botucatu - Unesp
ClinicalTrials.gov Identifier: NCT00499434     History of Changes
Other Study ID Numbers: upeclin/HC/FMB-Unesp-14
Study First Received: July 10, 2007
Last Updated: December 3, 2009
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by UPECLIN HC FM Botucatu Unesp:
aids

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014