Occult Hepatitis B Virus Infection and HBV Reactivation After Switching to Long Acting Therapy in Patients With HIV-1 (OBILART)

December 10, 2024 updated by: Castagna Antonella, IRCCS San Raffaele

Occult Hepatitis B Virus Infection and HBV Reactivation After Switching to Long Acting Therapy in Patients Living With HIV-1

The primary objective of the present project will be to investigate the risk of HBV reactivation (from virological reactivation to overt HBV infection) in HIV-1 carriers with occult HBV infection (OBI, is characterized by the absence of surface antigenemia, HBsAg negativity, with the presence of HBV-core antibody, HBcAb) and switching from antiretroviral therapy (ART) including nucleos(t)ides to long-acting formulation.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Observational prospective, multicenter, single-arm study with additional procedure in people living with HIV-1 and having serological markers of previous HBV infection: anti-core antibodies and/or antibodies against surface antigen (HBsAb) and switching from nucleoside analogue therapy to long-acting therapy including cabotegravir (CAB, HIV-1 integrase inhibitor) + rilpivirine (RPV, non-nucleoside HIV-1 reverse transcriptase inhibitor) intramuscularly 1 time every 2 months.

Primary Objective To study the risk of HBV reactivation from the phase of possible virological reactivation (HBV-DNA >=10 IU/mL), when the liver enzymes are within normal limits to overt HBV infection. Overt HBV infection is characterized by positive HBV-DNA, possible positivity of surface antigen (HBsAg) with or without altered liver enzymes in HIV-1 patients with OBI, with switch from ART, which includes nucleos(t)ide analogues active on the two HIV/HBV viruses, to the long-term formulation in which nucleos(t)ide analogues active on the two viruses are not included.

Secondary Objectives

  • To evaluate the effect, in the context of HBV reactivation, of HBV-RNA as a surrogate marker of the transcriptional activity of the covalently closed circular (cccDNA) which is present as an HBV replication intermediate at the hepatocyte level.
  • Examine the mutational profile of HBV domains (pre-S1 and S genes, X gene), mutations in the nucleocapsid promoter region and the pre-core/core variant, capable of influencing HBV replication efficiency, including also the analysis of mutants characterized as viral escape.

Exploratory Objectives To study the mutational profile of the regions of the hepatitis B virus (HBV) able to influence replication efficiency.

The study will include subjects living with HIV, followed at the San Luigi Center (Infectious Diseases), IRCCS Ospedale San Raffaele in Milan, Integrated Infectious Risk Management Department, Policlinico S. Orsola-Malpighi in Bologna, and the Department of Mental and Physical Health and Medicine prevention, University of Campania L. Vanvitelli of Naples, who agree to the switch from the current antiretroviral regimen which includes drugs active on HIV/HBV to long acting therapy.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
      • Milan, Italy, 20127
        • IRCCS San Raffaele O.U. Infectious Diseases
      • Napoli, Italy, 80138
        • Università Luigi Vanvitelli della Campania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

50 subjects will participate to the study, 30 subjects enrolled at the San Luigi Center (Unit of Infectious Diseases), IRCCS Ospedale San Raffaele in Milan, 10 subjects enrolled at Integrated Infectious Risk Management Department, Policlinico S. Orsola-Malpighi in Bologna, and 10 at the Department of Mental and Physical Health and Medicine prevention, University of Campania L. Vanvitelli of Naples.

Description

Inclusion Criteria:

  • Age > 18 years
  • Informed consent to participate in the study
  • HIV infection
  • Stable antiretroviral therapy (ART) in the six months prior to enrollment without virological failure defined by HIV-RNA>50 copies/mL in at least two consecutive determinations
  • Positive HBV anti-core antibodies (HBcAb) in the absence of hepatitis B surface antigen (HBsAg)
  • Absence of mutations associated with resistance to integrase inhibitors (INSTIs) and reverse transcriptase inhibitors (NNRTIs) by HIV genotypic resistance testing
  • CD4 Nadir >200 cells/mm3

Exclusion Criteria:

  • Any contraindications to the use of one or more long-acting drugs
  • Non-expression or withdrawal of informed consent to participate in the study
  • Pregnancy
  • Lack of HIV genotypic resistance testing
  • Virological failure (HIV-RNA >50 copies/mL in at least 2 consecutive determinations) in the 6 months prior to enrollment
  • Therapeutic interruptions in the six months prior to enrollment, excluding interruptions lasting less than a month due to tolerability
  • CD4 Nadir =<200 cells/mm3
  • Presence of biochemical signs of hepatocellular necrosis (AST, ALT > normal values as indicated in laboratory tests).
  • Cirrhosis and/or fibrosis score >F3 assessed by transient elastography (FibroScan).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Subjects living with HIV switching to long acting therapy
The study will include subjects living with HIV, followed at the San Luigi Center (Infectious Diseases), IRCCS Ospedale San Raffaele in Milan, Integrated Infectious Risk Management Department, Policlinico S. Orsola-Malpighi in Bologna, and the Department of Mental and Physical Health and Medicine prevention, University of Campania L. Vanvitelli of Naples, who agree to the switch from the current antiretroviral regimen which includes drugs active on HIV/HBV to long acting therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantification of hepatitis B DNA (HBV-DNA)
Time Frame: Baseline (start of long-acting therapy) weeks 12, 24 and 48
HBV-DNA increase respect to baseline viremia (=>10 IU/mL) according to different time points (W12, W24, W48) after the start of LART.
Baseline (start of long-acting therapy) weeks 12, 24 and 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantification of hepatitis B RNA (HBV-RNA)
Time Frame: Baseline and at weeks 12, 24 and 48
any concomitant HBV-RNA increase respect to baseline value by measurement of HBV- RNA at different time points (W12, W24, W48).
Baseline and at weeks 12, 24 and 48
HBV mutational pattern by direct sequencing (Sanger)
Time Frame: Baseline and at weeks 12, 24 and 48
the mutational pattern of HBV genome (S, pre-C/C, X and polymerase regions) will be evaluated in positive HBV-DNA samples
Baseline and at weeks 12, 24 and 48

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of number of amino acid and/or nucleotide substitution.
Time Frame: Baseline (start of long-acting therapy) weeks 12, 24 and 48
Measurement of number of amino acid and/or nucleotide substitution tostudy the mutational profile of the regions of the hepatitis B virus (HBV) able to influence replication efficiency.
Baseline (start of long-acting therapy) weeks 12, 24 and 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Collaborators

IRCCS Azienda Ospedaliero-Universitaria di Bologna
Università Luigi Vanvitelli della Campania

Investigators

  • Principal Investigator: Antonella Castagna, Prof, MD, IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 20, 2025

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

December 5, 2024

First Submitted That Met QC Criteria

December 10, 2024

First Posted (Estimated)

December 11, 2024

Study Record Updates

Last Update Posted (Estimated)

December 11, 2024

Last Update Submitted That Met QC Criteria

December 10, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRCCS San Raffaele

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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