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HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy

  1. Author:
    Zerbato, Jennifer M
    Avihingsanon, Anchalee
    Singh, Kasha P
    Zhao, Wei
    Deleage,Claire
    Rosen, Elias
    Cottrell, Mackenzie L
    Rhodes, Ajantha
    Dantanarayana, Ashanti
    Tumpach, Carolin
    Tennakoon, Surekha
    Crane, Megan
    Price, David J
    Braat, Sabine
    Mason, Hugh
    Roche, Michael
    Kashuba, Angela D M
    Revill, Peter A
    Audsley, Jennifer
    Lewin, Sharon R

  2. Author Address

    Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA., Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA., National Centre for Infections in Cancer, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Centre for Epidemiology & Biostatistics, Melbourne School of Population & Global Health, University of Melbourne, Melbourne, Australia., Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Centre for Epidemiology & Biostatistics, Melbourne School of Population & Global Health, University of Melbourne, Melbourne, Australia; MISCH (Methods and Implementation Support for Clinical Health) Research Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia., Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia., Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia. Electronic address: sharon.lewin@unimelb.edu.au.,
    1. Year: 2022
    2. Date: Dec 08
    3. Epub Date: 2022 12 08
  2. Journal: EBioMedicine
    1. 87
    2. Pages: 104391
  4. Type of Article: Article
  5. Article Number: 104391
  1. Abstract:

    HIV can infect multiple cells in the liver including hepatocytes, Kupffer cells and infiltrating T cells, but whether HIV can persist in the liver in people with HIV (PWH) on suppressive antiretroviral therapy (ART) remains unknown. In a prospective longitudinal cohort of PWH and hepatitis B virus (HBV) co-infection living in Bangkok, Thailand, we collected blood and liver biopsies from 18 participants prior to and following ART and quantified HIV and HBV persistence using quantitative (q)PCR and RNA/DNAscope. Antiretroviral (ARV) drug levels were quantified using mass spectroscopy. In liver biopsies taken prior to ART, HIV DNA and HIV RNA were detected by qPCR in 53% (9/17) and 47% (8/17) of participants respectively. Following a median ART duration of 3.4 years, HIV DNA was detected in liver in 61% (11/18) of participants by either qPCR, DNAscope or both, but only at very low and non-quantifiable levels. Using immunohistochemistry, HIV DNA was observed in both hepatocytes and liver infiltrating CD4+ T cells on ART. HIV RNA was not detected in liver biopsies collected on ART, by either qPCR or RNAscope. All ARVs were clearly detected in liver tissue. Persistence of HIV DNA in liver in PWH on ART represents an additional reservoir that warrants further investigation. National Health and Medical Research Council of Australia (Project Grant APP1101836, 1149990, and 1135851); This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

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  2. DOI: 10.1016/j.ebiom.2022.104391
  3. PMID: 36502576
  4. PII : S2352-3964(22)00573-4

Library Notes

  1. Fiscal Year: FY2022-2023
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