Study on Immunopathogenesis in HIV and Hepatitis C Coinfection

NCT01296529 | Completed

• 1 other identifier: 100517002
• Study Type: observational
• Target: 59
• Locations: 1 country
• Sites: 2

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. 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. 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.

Conditions

HIV Infection; Hepatitis C Infection; Fibrosis; Inflammation

Outcome Measures

Primary Outcomes (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

  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.

  6 months

Study Arms (4)

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Pregnancy
• History of End Stage Liver Disease
• Active hepatitis B infection
• Severe illness / discretion of investigator
• BMI ≥ 35

Sponsors & Collaborators

• Rush University Medical Center: lead
• Ruth M. Rothstein CORE Center: collaborator
• Merck Sharp & Dohme LLC: collaborator
• University of North Carolina, Chapel Hill: collaborator

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Ruth M. Rothstein CORE Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• 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

  RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and plasma

MeSH Terms

Conditions

HIV Infections; Hepatitis C; Fibrosis; Inflammation

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gregory Huhn, MD, MPHTM

  The Ruth M. Rothstein CORE Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: February 15, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: July 1, 2012
• Last Updated: December 12, 2012

Record last verified: 2012-12

Locations

US (2)