Study on Immunopathogenesis in HIV and Hepatitis C Coinfection

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Rush University Medical Center, Chicago, Illinois, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

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.

Sponsors and collaborators

Lead sponsor

Rush University Medical Center

Other

Collaborators

Merck Sharp & Dohme LLC
Ruth M. Rothstein CORE Center
University of North Carolina, Chapel Hill

Registry information

Official study title

A Pilot Study on Immunopathogenesis in HIV and Hepatitis C Coinfection

Important dates

Study start: 2011
Primary completion: 2011
Study completion: 2012
First posted: Feb 15, 2011
Registry last updated: Dec 12, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed