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Study on Immunopathogenesis in HIV and Hepatitis C Coinfection

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ClinicalTrials.gov Identifier: NCT01296529
Recruitment Status : Completed
First Posted : February 15, 2011
Last Update Posted : December 12, 2012
Sponsor:
Collaborators:
Ruth M. Rothstein CORE Center
Merck Sharp & Dohme Corp.
University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
Gregory Huhn, Rush University Medical Center

Study Description
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

Liver-related death is the leading cause of mortality in HIV-infected individuals with CD4+ cell counts over 200, and hepatitis C virus (HCV) infection is the greatest risk for liver-related mortality in HIV-positive patients. Compared to HCV monoinfected individuals, patients with HIV and HCV coinfection experience accelerated progression of liver fibrosis, which can lead to higher incidence of cirrhosis, end stage liver disease (ESLD), and death. Changes in CD8+ T-cell activation, inflammatory cytokines, and serum markers of tissue injury may offer an immunologic platform to determine factors associated with progressive liver fibrosis in coinfected patients. In this cross-sectional study we will evaluate whether HIV and HCV coinfection patients with well-controlled HIV infection who have an undetectable viral load exhibit abnormal levels of inflammation and immune activation, potentially contributing to advanced liver fibrosis. Comparative groups include coinfected patients successfully treated for hepatitis C, or who have absence of hepatitis C viremia through spontaneous clearance, hepatitis C monoinfected patients, and HIV-positive patients with well-controlled HIV infection without hepatitis C. Liver fibrosis will be measured by non-invasive methods.

The primary objectives of this study are:

  1. To determine if there are differences in markers of inflammation and immune activation in subsets of patients with HIV, hepatitis C, and HIV and hepatitis C coinfection.
  2. To assess the stage of liver fibrosis using non-invasive methods in subsets of patients with hepatitis C and HIV and hepatitis C coinfection and compare the degree of liver fibrosis with levels of inflammation and immune activation.

Condition or disease
HIV Infection Hepatitis C Infection Fibrosis Inflammation

Study Design
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Study Type : Observational
Actual Enrollment : 59 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: A Pilot Study on Immunopathogenesis in HIV and Hepatitis C Coinfection
Study Start Date : July 2011
Actual Primary Completion Date : December 2011
Actual Study Completion Date : July 2012

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U.S. FDA Resources

Groups and Cohorts
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
HIV monoinfection
Evidence should include a copy of a laboratory report of testing positive for HIV antibodies and/or HIV viral RNA, and a negative antibody test for HCV
HCV monoinfection
Evidence should include a copy of a laboratory report of testing positive for HCV antibodies and HCV viral RNA, and a negative antibody test for HIV
HIV and HCV coinfection
Evidence should include a copy of a laboratory report of testing positive for HIV or HIV viral RNA, and positive tests for HCV antibodies and HCV RNA.
HIV/HCV coinfection with HCV clearance
Evidence should include a copy of a laboratory report of testing positive for HIV or HIV viral RNA, a positive tests for HCV antibodies, and undetectable HCV RNA without hepatitis C treatment (spontaneous clearance) or >6 months after hepatitis therapy (sustained virologic response)


Outcome Measures
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Primary Outcome Measures :
  1. Comparison of liver fibrosis with levels of inflammation and immune activation in subsets of patients with HIV, hepatitis C, and HIV and hepatitis C coinfection [ Time Frame: 6 months ]
    Assess the associations between liver fibrosis as the dependent variable measured as a fibrosis score in kPa with predictor variables (markers of inflammation [IL-1β, IL-6, IL-8, IL10, IL-12, IL-15, IL-17, IL-21, IP10, IFN-γ, TNF-α, macrophage inflammatory protein 1 alpha (CCR7), hsCRP], immune activation and senescence [CD3, CD4, CD8, HLA DR, CD38, Ki67 CD45RA, CCR7, CD28, CD57], and tissue injury [tissue factor]) for groups b, c, and d separately by using linear regression models. Group a is the control arm for the dependent variable.


Biospecimen Retention:   Samples Without DNA
serum and plasma

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
a) HIV monoinfected; b) hepatitis C monoinfected; c) HIV/HCV coinfected untreated for hepatitis C; and d) HIV/HCV coinfected with clearance of HCV virus. Subjects will be all matched by age and estimated duration of hepatitis C infection where applicable. In addition, subjects in strata a and c will be matched by length of ARV therapy and CD4 count first established in strata d observed immediately before the initiation of successful hepatitis C therapy or documentation of negative HCV RNA in subjects with spontaneous clearance. Subjects in strata b will be matched in the same manner to strata d, except length of ARV therapy and CD4 count variables will not be considered. All subjects with HIV infection will be on HAART with undetectable viral loads.
Criteria

Inclusion Criteria:

  • Strata a (n=15): Patients must be infected with HIV-1 infection without HCV. Evidence should include a copy of a laboratory report of testing positive for HIV antibodies and/or HIV viral RNA, and a negative antibody test for HCV
  • Strata b (n=15): Patients must be infected with HCV infection without HIV. Evidence should include a copy of a laboratory report of testing positive for HCV antibodies and HCV viral RNA, and a negative antibody test for HIV
  • Strata c (n=15): Patients must be co-infected with HIV & HCV prior to enrollment. Evidence should include a copy of a laboratory report of testing positive for HIV or HIV viral RNA, and positive tests for HCV antibodies and HCV RNA.
  • Strata d (n=15): Patients must be co-infected with HIV & HCV prior to enrollment, with verification of successful treatment or spontaneous clearance for hepatitis C infection. Evidence should include a copy of a laboratory report of testing positive for HIV or HIV viral RNA, a positive tests for HCV antibodies, and undetectable HCV RNA without hepatitis C treatment (spontaneous clearance) or >6 months after hepatitis therapy (sustained virologic response)
  • Patients should not have ESLD and/or HCC within 6 months of enrollment. Evidence should at least include a physical examination by certified medical practitioner, negative ultrasound of the liver, and laboratory testing consistent with Child A and a Model for ESLD (MELD) ≤ 10. (Note: patients taking atazanavir may be enrolled with elevated total bilirubin if other Child and MELD criteria are normal.)
  • Treatment with antiretroviral drugs for at least 12 months
  • Undetectable HIV-1 RNA (<75 copies for at least 6 months)
  • Patients must consent to study procedures
  • Patients must be >18 years of age

Exclusion Criteria:

  • Pregnancy
  • History of End Stage Liver Disease
  • Active hepatitis B infection
  • Severe illness / discretion of investigator
  • BMI ≥ 35
Contacts and Locations
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT01296529


Locations
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Ruth M. Rothstein CORE Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Rush University Medical Center
Ruth M. Rothstein CORE Center
Merck Sharp & Dohme Corp.
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Gregory Huhn, MD, MPHTM The Ruth M. Rothstein CORE Center
More Information
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:
Hodowanec A, Brady KE, Gao W, Kincaid S, Plants J, Bahk M, Landay A, Huhn G. Differences in CD4+ T-cell Immune Activation in HIV, Hepatitis C (HCV), and HIV/HCV Coinfection Are Influenced by HIV and HCV Infection Status. Abstract MOPE011. 19th International AIDS Conference, Washington DC, July 23, 2012

Responsible Party: Gregory Huhn, MD, Rush University Medical Center
ClinicalTrials.gov Identifier: NCT01296529     History of Changes
Other Study ID Numbers: 100517002
First Posted: February 15, 2011    Key Record Dates
Last Update Posted: December 12, 2012
Last Verified: December 2012

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Inflammation
HIV Infections
Coinfection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
 Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Parasitic Diseases