دورية أكاديمية
HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy.
العنوان: | HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy. |
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المؤلفون: | Zerbato JM; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Avihingsanon A; HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Singh KP; 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., Zhao W; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Deleage C; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA., Rosen E; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA., Cottrell ML; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA., Rhodes A; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Dantanarayana A; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Tumpach C; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Tennakoon S; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Crane M; National Centre for Infections in Cancer, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia., Price DJ; 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., Braat S; 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., Mason H; Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia., Roche M; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Kashuba ADM; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA., Revill PA; Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia., Audsley J; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Lewin SR; 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. |
المصدر: | EBioMedicine [EBioMedicine] 2023 Jan; Vol. 87, pp. 104391. Date of Electronic Publication: 2022 Dec 08. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2014]- |
مواضيع طبية MeSH: | Coinfection* , Hepatitis B*/complications , HIV Infections*/complications , HIV Infections*/drug therapy, Humans ; Prospective Studies ; Thailand ; Hepatitis B virus/genetics ; Anti-Retroviral Agents/pharmacology ; Anti-Retroviral Agents/therapeutic use ; DNA, Viral/genetics ; Hepatocytes |
مستخلص: | Background: 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. Methods: 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. Findings: 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. Interpretation: Persistence of HIV DNA in liver in PWH on ART represents an additional reservoir that warrants further investigation. Funding: 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. Competing Interests: Declaration of interests SRL has received consultancy fees from ViiV; and Honoraria from Gilead and Merck. There are no additional conflicts of interest to declare. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.) |
فهرسة مساهمة: | Keywords: HIV reservoir; HIV-HBV co-infection; Hepatocytes; Liver biopsy |
المشرفين على المادة: | 0 (Anti-Retroviral Agents) 0 (DNA, Viral) |
تواريخ الأحداث: | Date Created: 20221211 Date Completed: 20230120 Latest Revision: 20230120 |
رمز التحديث: | 20230120 |
مُعرف محوري في PubMed: | PMC9763386 |
DOI: | 10.1016/j.ebiom.2022.104391 |
PMID: | 36502576 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2352-3964 |
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DOI: | 10.1016/j.ebiom.2022.104391 |