HBV-HIV Coinfection Research Network

NCT ID: NCT01924455

Last Updated: 2023-05-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 139 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2019-03-31

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.

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.

Conditions

Hepatitis B; Human Immunodeficiency Virus

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

HBV-HIV coinfected subjects

HBV-HIV coinfected subjects seen at one of 7 participating centers.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

-

Exclusion Criteria

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Sterling, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

University of California

San Francisco, California, United States

Johns Hopkins University

Baltimore, Maryland, United States

NIDDK

Bethesda, Maryland, United States

Mass General Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

UT Southwestern

Dallas, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Toronto Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Lisker-Melman M, King WC, Ghany MG, Chung RT, Hinerman AS, Cloherty GA, Khalili M, Jain MK, Sulkowski M, Sterling RK. Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia. J Viral Hepat. 2023 Aug;30(8):700-709. doi: 10.1111/jvh.13857. Epub 2023 Jun 6.

Reference Type: DERIVED

PMID: 37278302 (View on PubMed)

Lisker-Melman M, Wahed AS, Ghany MG, Chung RT, King WC, Kleiner DE, Bhan AK, Khalili M, Jain MK, Sulkowski M, Wong DK, Cloherty G, Sterling RK. HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy. Hepatology. 2023 Feb 1;77(2):594-605. doi: 10.1002/hep.32634. Epub 2022 Jul 21.

Reference Type: DERIVED

PMID: 35770681 (View on PubMed)

Sterling RK, King WC, Khalili M, Chung RT, Sulkowski M, Jain MK, Lisker-Melman M, Ghany MG, Wong DK, Hinerman AS, Bhan AK, Wahed AS, Kleiner DE; HBV-HIV Cohort Study of the Hepatitis B Research Network. A Prospective Study Evaluating Changes in Histology, Clinical and Virologic Outcomes in HBV-HIV Co-infected Adults in North America. Hepatology. 2021 Sep;74(3):1174-1189. doi: 10.1002/hep.31823. Epub 2021 Aug 25.

Reference Type: DERIVED

PMID: 33743541 (View on PubMed)

Sterling RK, King WC, Khalili M, Kleiner DE, Hinerman AS, Sulkowski M, Chung RT, Jain MK, Lisker-Melman MA, Wong DK, Ghany MG; HBV-HIV Cohort Study of the Hepatitis B Research Network. Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV-HIV Co-infected Adults. Dig Dis Sci. 2022 Feb;67(2):676-688. doi: 10.1007/s10620-021-06860-3. Epub 2021 Feb 8.

Reference Type: DERIVED

PMID: 33559089 (View on PubMed)

Khalili M, King WC, Kleiner DE, Jain MK, Chung RT, Sulkowski M, Lisker-Melman M, Wong DK, Ghany M, Sanyal A, Sterling RK. Fatty Liver Disease in a Prospective North American Cohort of Adults With Human Immunodeficiency Virus and Hepatitis B Virus Coinfection. Clin Infect Dis. 2021 Nov 2;73(9):e3275-e3285. doi: 10.1093/cid/ciaa1303.

Reference Type: DERIVED

PMID: 32869840 (View on PubMed)

Sterling RK, King WC, Wahed AS, Kleiner DE, Khalili M, Sulkowski M, Chung RT, Jain MK, Lisker-Melman M, Wong DK, Ghany MG; HIV-HBV Cohort Study of the Hepatitis B Research Network. Evaluating Noninvasive Markers to Identify Advanced Fibrosis by Liver Biopsy in HBV/HIV Co-infected Adults. Hepatology. 2020 Feb;71(2):411-421. doi: 10.1002/hep.30825. Epub 2019 Aug 19.

Reference Type: DERIVED

PMID: 31220357 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

DK094818

Identifier Type: OTHER

Identifier Source: secondary_id

HM20000444

Identifier Type: -

Identifier Source: org_study_id