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

Not yet recruiting

• Conditions: HBV (Hepatitis B Virus); HIV Infection

• Registration Number: NCT06728917
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

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.

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 Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-10
• Last Update Submitted: 2024-12-10
• Study First Posted: 2024-12-11
• Last Update Posted: 2024-12-11
• Study Start: 2025-01-20
• Primary Completion: 2025-04-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantification of hepatitis B DNA (HBV-DNA)	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.

Secondary Outcome Measures

Name	Time	Method
Quantification of hepatitis B RNA (HBV-RNA)	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).
HBV mutational pattern by direct sequencing (Sanger)	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

Trial Locations

Locations (3)

IRCCS Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Italy

IRCCS San Raffaele O.U. Infectious Diseases; 🇮🇹 Milan, Italy

Università Luigi Vanvitelli della Campania; 🇮🇹 Napoli, Italy