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

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ClinicalTrials.gov Identifier: NCT00499434
Recruitment Status : Unknown
Verified December 2009 by UPECLIN HC FM Botucatu Unesp.
Recruitment status was:  Active, not recruiting
First Posted : July 11, 2007
Last Update Posted : December 4, 2009
Sponsor:
Information provided by:

Study Description
Brief 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.

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

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.


Study Design

Study Type : Observational
Estimated Enrollment : 110 participants
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
Study Start Date : August 2007
Estimated Primary Completion Date : January 2009
Estimated Study Completion Date : February 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts


Outcome Measures

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
First Posted: July 11, 2007    Key Record Dates
Last Update Posted: December 4, 2009
Last Verified: December 2009

Keywords provided by UPECLIN HC FM Botucatu Unesp:
aids

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