Trial record 10 of 30 for:    " July 17, 2013":" August 16, 2013"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

HBV-HIV Coinfection Research Network

This study is not yet open for participant recruitment.
Verified February 2014 by Virginia Commonwealth University
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01924455
First received: August 12, 2013
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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
Hepatitis B
Human Immunodeficiency Virus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: HBV-HIV Coinfection Research Network

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Liver disease severity [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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:
  • Outcome of viral suppression [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 250
Study Start Date: April 2014
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
HBV-HIV coinfected subjects
HBV-HIV coinfected subjects seen at one of 7 participating centers.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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.

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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.

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01924455

Contacts
Contact: Richard Sterling, MD, MSc rksterli@vcu.edu

Locations
United States, California
University of California Not yet recruiting
San Francisco, California, United States
Principal Investigator: Mandana Khalili, MD         
United States, Maryland
Johns Hopkins University Not yet recruiting
Balitmore, Maryland, United States
Principal Investigator: Mark Sulkowski, MD         
United States, Massachusetts
Mass General Hospital Not yet recruiting
Boston, Massachusetts, United States
Principal Investigator: Raymond Chung, MD         
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States
Principal Investigator: Mauricio Lisker-Melman, MD         
United States, Texas
UT Southwestern Not yet recruiting
Dallas, Texas, United States
Principal Investigator: Mamta Jain, MD         
United States, Virginia
Virginia Commonwealth University Not yet recruiting
Richmond, Virginia, United States
Principal Investigator: Richard Sterling, MD, MSc         
Canada, Ontario
Toronto Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
Virginia Commonwealth University
  More Information

Additional Information:
No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01924455     History of Changes
Other Study ID Numbers: DK094818
Study First Received: August 12, 2013
Last Updated: February 7, 2014
Health Authority: United States: Federal Government

Keywords provided by Virginia Commonwealth University:
HIV
HBV

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

ClinicalTrials.gov processed this record on April 23, 2014