HBV-HIV Coinfection Research Network

Hepatitis B Clinical Trial

Official title:

HBV-HIV Coinfection Research Network

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01924455
• Other study ID #: HM20000444
• Secondary ID: DK094818
• Status: Completed
• Start date: April 2014
• Est. completion date: March 31, 2019

Study information

• Verified date: May 2023
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: March 31, 2019
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

-

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Coinfection
• Hepatitis B
• HIV Infections
• Human Immunodeficiency Virus

Locations

Country	Name	City	State
Canada	Toronto Hospital	Toronto	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	NIDDK	Bethesda	Maryland
United States	Mass General Hospital	Boston	Massachusetts
United States	UT Southwestern	Dallas	Texas
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	University of California	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Commonwealth University

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	4 years
Secondary	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.	4 years

External Links

•   HBRN website