Prospective Cohort of HIV/HBV-coinfected Patients in Europe

• Conditions: HIV Infections; Hepatitis B; Coinfection

• Registration Number: NCT04984772
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

The overall aim of the project is to establish an international multi-cohort research platform of HIV/HBV-coinfected individuals treated with tenofovir to improve our understanding of the determinants of treatment outcomes.

Detailed Description

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals and the progression of liver disease is accelerated in this population compared to HBV-monoinfected individuals. Tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) as part of antiretroviral therapy (ART) suppresses HBV viral load in most patients. However, risk factors of suboptimal virological response to TDF/TAF and predictors of hepatitis B surface antigen (HBsAg) loss remain unclear. While novel drugs for HBV therapy are being developed, a more thorough understanding of the factors associated with optimal outcomes is urgent. Euro-B considers all HIV/HBV-coinfected participants from EuroSIDA, the Swiss HIV cohort study and French, Spanish and German HIV-HBV cohorts treated with TDF/TAF for inclusion.

The overall aim of the project is to establish an international prospective multi-cohort research platform of HIV/HBV-coinfected individuals to improve our understanding of the determinants of treatment outcomes, including functional cure of HBV infection. Specifically, we aim to:

1. evaluate HBV virological suppression, hepatitis B e antigen (HBeAg) and HBsAg loss as well as the course of quantitative HBsAg (qHBsAg) levels during TDF/TAF-containing antiretroviral therapy

2. evaluate predictors of HBsAg loss and its correlation with Hepatitis B core-related antigen (HBcrAg) and pre-genomic RNA (pgRNA) levels

3. explore risk factors for low-level HBV replication after 2 years of therapy

4. describe changes in liver fibrosis stage and rates of transaminase normalization over time and according to HBV therapy outcome

5. assess rates and reasons of treatment interruptions or changes.

Study Timeline

• Study Start: 2001-10-02
• Study First Submitted: 2021-06-30
• Study First Submitted QC: 2021-07-28
• Study First Posted: 2021-08-02
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-30
• Last Update Posted: 2023-12-01
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 1107

Inclusion Criteria

• Study participant from contributing cohort
• 2 positive HBsAg tests more than 6 months apart
• At least 2 data points (baseline and 2 years after TDF/TAF start either as available data or stored sample

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
HBV suppression	2 years of TDF/TAF-containing treatment and last available timepoint	Proportion of participants achieving undetectable HBV DNA
Liver fibrosis change	2 years of TDF/TAF-containing treatment and last available timepoint	Proportion of participants with a change in liver fibrosis stage
HBsAg loss	2 years of TDF/TAF-containing treatment and last available timepoint	Proportion of participants with a negative HBsAg measurement
HBeAg loss	2 years of TDF/TAF-containing treatment and last available timepoint	Proportion of participants with a negative HBeAg measurement
Treatment interruption or change	2 years of TDF/TAF-containing treatment and last available timepoint	Assessments of rates and reasons for treatment interruptions or changes
Transaminase normalization	2 years of TDF/TAF-containing treatment and last available timepoint	Proportion of participants with transaminase normalization