Occult Hepatitis B Virus Infection and HBV Reactivation After Switching to Long Acting Therapy in Patients With HIV-1
NCT ID: NCT06728917
Last Updated: 2024-12-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
50 participants
OBSERVATIONAL
2025-01-20
2025-11-30
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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OTHER
PROSPECTIVE
Study Groups
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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.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* 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
* 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).
18 Years
ALL
No
Sponsors
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IRCCS Azienda Ospedaliero-Universitaria di Bologna
OTHER
Università Luigi Vanvitelli della Campania
UNKNOWN
IRCCS San Raffaele
OTHER
Responsible Party
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Castagna Antonella
Prof
Principal Investigators
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Antonella Castagna, Prof, MD
Role: PRINCIPAL_INVESTIGATOR
IRCCS San Raffaele
Locations
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IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, , Italy
IRCCS San Raffaele O.U. Infectious Diseases
Milan, , Italy
Università Luigi Vanvitelli della Campania
Napoli, , Italy
Countries
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Central Contacts
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References
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Morsica G, Bagaglio S, Cicconi P, Capobianchi MR, Pellizzer G, Caramello P, Orani A, Moioli C, Rizzardini G, Uberti-Foppa C, Puoti M, Monforte AD; Hepa I.C.o.N.A the Icona Foundation Study Groups. Viral interference between hepatitis B, C, and D viruses in dual and triple infections in HIV-positive patients. J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):574-81. doi: 10.1097/QAI.0b013e3181add592.
Jaeger H, Overton ET, Richmond G, Rizzardini G, Andrade-Villanueva JF, Mngqibisa R, Hermida AO, Thalme A, Belonosova E, Ajana F, Benn PD, Wang Y, Hudson KJ, Espanol CM, Ford SL, Crauwels H, Margolis DA, Talarico CL, Smith KY, van Eygen V, Van Solingen-Ristea R, Vanveggel S, Spreen WR. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021 Nov;8(11):e679-e689. doi: 10.1016/S2352-3018(21)00185-5. Epub 2021 Oct 11.
Huang H, Wang J, Li W, Chen R, Chen X, Zhang F, Xu D, Lu F. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naive HBV-infected individuals. J Clin Virol. 2018 Feb-Mar;99-100:71-78. doi: 10.1016/j.jcv.2017.12.016. Epub 2018 Jan 6.
Carey I, Gersch J, Wang B, Moigboi C, Kuhns M, Cloherty G, Dusheiko G, Agarwal K. Pregenomic HBV RNA and Hepatitis B Core-Related Antigen Predict Outcomes in Hepatitis B e Antigen-Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy. Hepatology. 2020 Jul;72(1):42-57. doi: 10.1002/hep.31026.
Bagaglio S, Bianchi G, Danise A, Porrino L, Uberti-Foppa C, Lazzarin A, Castagna A, Morsica G. Longitudinal evaluation of occult hepatitis B infection in HIV-1 infected individuals during highly active antiretroviral treatment interruption and after HAART resumption. Infection. 2011 Apr;39(2):121-6. doi: 10.1007/s15010-011-0093-9. Epub 2011 Mar 22.
Bagaglio S, Porrino L, Lazzarin A, Morsica G. Molecular characterization of occult and overt hepatitis B (HBV) infection in an HIV-infected person with reactivation of HBV after antiretroviral treatment interruption. Infection. 2010 Oct;38(5):417-21. doi: 10.1007/s15010-010-0032-1. Epub 2010 Jun 9.
Clark SJ, Creighton S, Horner M, Smith HM, Portmann B, Taylor C, Cramp ME. Reactivation of latent hepatitis B virus infection with HIV-related immunosuppression. Int J STD AIDS. 2006 Jan;17(1):67-9. doi: 10.1258/095646206775220612.
Chamorro AJ, Casado JL, Bellido D, Moreno S. Reactivation of hepatitis B in an HIV-infected patient with antibodies against hepatitis B core antigen as the only serological marker. Eur J Clin Microbiol Infect Dis. 2005 Jul;24(7):492-4. doi: 10.1007/s10096-005-1355-1.
Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calo F, Coppola N. Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases. J Clin Med. 2021 Nov 8;10(21):5201. doi: 10.3390/jcm10215201.
Hu KQ. Occult hepatitis B virus infection and its clinical implications. J Viral Hepat. 2002 Jul;9(4):243-57. doi: 10.1046/j.1365-2893.2002.00344.x.
Mulrooney-Cousins PM, Michalak TI. Persistent occult hepatitis B virus infection: experimental findings and clinical implications. World J Gastroenterol. 2007 Nov 21;13(43):5682-6. doi: 10.3748/wjg.v13.i43.5682.
Ramezani A, Mohraz M, Aghakhani A, Banifazl M, Eslamifar A, Khadem-Sadegh A, Velayati AA. Frequency of isolated hepatitis B core antibody in HIV-hepatitis C virus co-infected individuals. Int J STD AIDS. 2009 May;20(5):336-8. doi: 10.1258/ijsa.2008.008377.
Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol. 2020 Dec;92(12):2917-2929. doi: 10.1002/jmv.25867. Epub 2020 Jun 29.
Santos EA, Yoshida CF, Rolla VC, Mendes JM, Vieira IF, Arabe J, Gomes SA. Frequent occult hepatitis B virus infection in patients infected with human immunodeficiency virus type 1. Eur J Clin Microbiol Infect Dis. 2003 Feb;22(2):92-8. doi: 10.1007/s10096-002-0868-0. Epub 2003 Feb 18.
Nunez M, Rios P, Perez-Olmeda M, Soriano V. Lack of 'occult' hepatitis B virus infection in HIV-infected patients. AIDS. 2002 Oct 18;16(15):2099-101. doi: 10.1097/00002030-200210180-00024. No abstract available.
Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007 Jan;46(1):160-70. doi: 10.1016/j.jhep.2006.10.007. Epub 2006 Nov 7.
Other Identifiers
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IRCCS San Raffaele
Identifier Type: -
Identifier Source: org_study_id