HBV-HIV Coinfection Research Network

Study Description

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

Brief Summary:

Despite effective ART that can suppress both HIV and HBV, HBV-related liver disease remains a significant co-morbidity in this population. Little is known about the histologic spectrum of liver disease, the significance of complete vs. incomplete HBV suppression, the utility of novel virologic and serum markers of disease severity, and the long-term renal and bone effects of TDF-based therapy. This proposal will address these important questions and impact the science and health of those coinfected with HBV-HIV.

Condition or disease
Hepatitis B; Human Immunodeficiency Virus

Detailed Description:

Since the introduction of highly active antiretroviral therapy (ART) in 1996, there has been a dramatic reduction in morbidity and mortality among those living with HIV. However, chronic liver disease due to coinfection with hepatitis B (HBV) or C (HCV) virus has emerged as the second leading cause of mortality among HIV-infected persons. The natural history of HBV infection is altered in those with HIV. Current guidelines recommend that most coinfected patients be treated for both HIV and HBV infection using combinations of ART that include tenofovir (TDF). Despite widespread adoption in the US, the effect of this regimen on long-term outcomes of HBV disease such as histologic severity, progression, and risk of emergence of resistant HBV variants, and the long term risks of TDF therapy remains unanswered. Further investigation is required to address the following important questions: (1) what is the proportion of HIV-coinfected patients who have incomplete viral suppression on TDF?; (2) is incomplete suppression of HBV acceptable in HIV coinfected persons and if so, what threshold HBV DNA level constitutes an adequate clinical goal?; (3) in view of the lack of acceptance of liver biopsy among HIV practitioners, can noninvasive markers accurately assess HBV disease activity and the impact of ART on disease progression?; (4) What are the long term risks of TDF-based therapy for HBV in HIV coinfection? In short, what are the risks and benefits of TDF-based therapy for CHB in patients with HIV coinfection? The NIH Hepatitis B Research Network (HBRN) is the first major effort to elucidate the natural history and treatment outcomes of persons with chronic HBV the US. The HBRN will not address the critical issue of HBV liver disease progression in HIV-infected persons because patients with HIV coinfection will be excluded. The current proposal, an approved ancillary study of the HBRN, offers a unique opportunity to fill major gaps in HBV-HIV knowledge and to compare HBV-HIV infected persons to those with HBV monoinfection participating in the HBRN. No other funded research network in North America has the expertise, patient population, and structure to carry out the proposed studies. The Specific Aims are: 1. Define the problem. We will clinically, histologically, serologically, and virologically characterize a well-defined cohort of HBV-HIV patients in North America in a cross-sectional manner; 2. Define the benefit of long term therapy. We will longitudinally determine the impact of complete vs. incomplete viral suppression on clinical and serologic outcomes, and histologic progression by paired biopsy and 2a. Define a threshold HBV DNA level associated with disease progression; 2b. Establish the utility of noninvasive assessment of hepatic fibrosis compared with biopsy; and 2c. Define the frequency of genotypic and phenotypic TDF resistance with long term therapy; and finally 3. Define the risk of long term therapy. We will assess the long term renal and bone effects of TDF-based therapy in the HBV-HIV cohort. Collectively, this study will fulfill many of the key priorities outlined in the NIH Action Plan for Liver Disease for HBV-HIV coinfection.

Study Design

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Study Type :	Observational
Estimated Enrollment :	250 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	HBV-HIV Coinfection Research Network
Study Start Date :	April 2014
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2019

Groups and Cohorts

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Group/Cohort
HBV-HIV coinfected subjects; HBV-HIV coinfected subjects seen at one of 7 participating centers.

Outcome Measures

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Primary Outcome Measures :

1. Liver disease severity [ Time Frame: 4 years ]
   We will clinically, histologically, serologically, and virologically characterize a well-defined cohort of HBV-HIV patients in North America in a cross-sectional manner

Secondary Outcome Measures :

1. Outcome of viral suppression [ Time Frame: 4 years ]
   1. We will longitudinally determine the impact of complete vs. incomplete viral suppression on clinical and serologic outcomes, and histologic progression by paired biopsy.
   2. Define a threshold HBV DNA level associated with disease progression.
   3. Establish the utility of noninvasive assessment of hepatic fibrosis compared with biopsy.
   4. Define the frequency of genotypic and phenotypic TDF resistance with long term therapy
   5. We will assess the long term renal and bone effects of TDF-based therapy in the HBV-HIV cohort.

Biospecimen Retention:   Samples With DNA

Serum at baseline and every 6 months for 4 years. Liver biopsy at baseline and year 4

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

HBV-HIV coinfection

Criteria

Inclusion Criteria: (1) Male and female subjects ≥ 18 years of age; (2) Serologic evidence of HIV infection by HIV antibody positivity or positive HIV-RNA > 6 months prior to screening (3) Serologic evidence of chronic hepatitis B infection by HBsAg positivity(4) Willingness to provide informed consent.

Exclusion Criteria: (1) Estimated life expectancy of less than one year based on clinical judgment of the investigator; (2) Hepatic decompensation as defined by presence of ascites or hepatic hydrothorax, variceal or portal hypertensive bleeding, hepatic encephalopathy, or Child-Turcotte-Pugh (CTP) score of 7 or above; (3) Hepatocellular carcinoma (HCC); (4) Anti-HCV positive; (5) History of solid organ or bone marrow transplantation; (6) Pregnant women; (7) Medical or social condition which in the opinion of the study physician would make the patient unsuitable for the study or will interfere with or prevent follow-up per protocol; (8) Unable or unwilling to return for follow-up visits; (9) Contraindications to liver biopsy.

Contacts and Locations

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

Contacts

Contact: Richard Sterling, MD, MSc		richard.sterling@vcuhealth.org

Locations

United States, California
University of California	Recruiting
San Francisco, California, United States
Principal Investigator: Mandana Khalili, MD
United States, Maryland
Johns Hopkins University	Recruiting
Baltimore, Maryland, United States
Principal Investigator: Mark Sulkowski, MD
NIDDK	Recruiting
Bethesda, Maryland, United States
Contact: Marc Ghany, MD
Principal Investigator: Marc Ghany, MD
United States, Massachusetts
Mass General Hospital	Recruiting
Boston, Massachusetts, United States
Principal Investigator: Raymond Chung, MD
United States, Missouri
Washington University	Recruiting
Saint Louis, Missouri, United States
Principal Investigator: Mauricio Lisker-Melman, MD
United States, Texas
UT Southwestern	Recruiting
Dallas, Texas, United States
Principal Investigator: Mamta Jain, MD
United States, Virginia
Virginia Commonwealth University	Recruiting
Richmond, Virginia, United States
Principal Investigator: Richard Sterling, MD, MSc
Canada, Ontario
Toronto Hospital	Recruiting
Toronto, Ontario, Canada
Principal Investigator: David Wong, MD

Sponsors and Collaborators

Virginia Commonwealth University

Investigators

Principal Investigator:	Richard Sterling, MD, MSc	Virginia Commonwealth University

More Information

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

Additional Information:

HBRN website 

Responsible Party:	Virginia Commonwealth University
ClinicalTrials.gov Identifier:	NCT01924455 History of Changes
Other Study ID Numbers:	HM20000444; DK094818 ( Other Identifier: NIH )
First Posted:	August 16, 2013
Last Update Posted:	August 8, 2017
Last Verified:	August 2017

Keywords provided by Virginia Commonwealth University:

HIV; HBV

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Hepatitis B; Immunologic Deficiency Syndromes; Coinfection; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases	Digestive System Diseases; Immune System Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases; Infection; Parasitic Diseases