Hepatitis BNCT01924455
HBV-HIV Coinfection Research Network
An observational study of Hepatitis B and Human Immunodeficiency Virus, run by Virginia Commonwealth University at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatitis B, Human Immunodeficiency Virus
- How many people
- 139 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Apr 2014to 31 Mar 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HBV-HIV coinfection
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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Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Johns Hopkins University
Baltimore, Maryland
NIDDK
Bethesda, Maryland
Mass General Hospital
Boston, Massachusetts
UT Southwestern
Dallas, Texas
Virginia Commonwealth University
Richmond, Virginia
University of California
San Francisco, California
Washington University
St Louis, Missouri
About this study
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.
Read the 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
- Keywords
- HIV, HBV
- Medical subject headings
- Hepatitis B, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HBV-HIV coinfected subjects | HBV-HIV coinfected subjects seen at one of 7 participating centers. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver disease severity
We will clinically, histologically, serologically, and virologically characterize a well-defined cohort of HBV-HIV patients in North America in a cross-sectional manner
Measured: 4 years
Secondary outcomes (1)
Outcome of viral suppression
- We will longitudinally determine the impact of complete vs. incomplete viral suppression on clinical and serologic outcomes, and histologic progression by paired biopsy.
- Define a threshold HBV DNA level associated with disease progression.
- Establish the utility of noninvasive assessment of hepatic fibrosis compared with biopsy.
- Define the frequency of genotypic and phenotypic TDF resistance with long term therapy
- We will assess the long term renal and bone effects of TDF-based therapy in the HBV-HIV cohort.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2013 (estimated)
- Study startApr 2014
- Primary completion31 Mar 2019
- Study completion31 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Sterling, MD, MSc, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924455
- Sponsor's protocol ID
- HM20000444
- Other IDs
- DK094818
- Status last verified
- May 2023
- First submitted
- 12 Aug 2013
- Last updated
- 16 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37278302Lisker-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.
PubMed 35770681Sterling 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.
PubMed 33743541Sterling 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.
PubMed 33559089Khalili 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.
PubMed 32869840Sterling 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.
PubMed 31220357
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HBV-HIV Coinfection Research Network
- ClinicalTrials.gov ID
- NCT01924455
- Acronym / sponsor ID
- HM20000444
- Conditions
- Hepatitis B, Human Immunodeficiency Virus
- Keywords
- HIV, HBV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 16 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBV-HIV coinfected subjects | – | –HBV-HIV coinfected subjects seen at one of 7 participating centers. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HBV-HIV coinfection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
1 secondary outcome
Outcome of viral suppression
Time frame: 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Derived from this study: PubMed 37278302Lisker-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.
- Derived from this study: PubMed 35770681Lisker-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.
- Derived from this study: PubMed 33743541Sterling 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.
- Derived from this study: PubMed 33559089Sterling 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.
- Derived from this study: PubMed 32869840Khalili 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.
- Derived from this study: PubMed 31220357Sterling 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Sterling, MD, MSc principal investigator
Virginia Commonwealth University
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B and Human Immunodeficiency Virus, run by Virginia Commonwealth University at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver disease severity (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01924455, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.