HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapyResearch in context
Jennifer M. Zerbato,
Anchalee Avihingsanon,
Kasha P. Singh,
Wei Zhao,
Claire Deleage,
Elias Rosen,
Mackenzie L. Cottrell,
Ajantha Rhodes,
Ashanti Dantanarayana,
Carolin Tumpach,
Surekha Tennakoon,
Megan Crane,
David J. Price,
Sabine Braat,
Hugh Mason,
Michael Roche,
Angela D.M. Kashuba,
Peter A. Revill,
Jennifer Audsley,
Sharon R. Lewin
Affiliations
Jennifer M. Zerbato
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Anchalee Avihingsanon
HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Kasha P. Singh
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
Wei Zhao
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Claire Deleage
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
Elias Rosen
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
Mackenzie L. Cottrell
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
Ajantha Rhodes
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Ashanti Dantanarayana
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Carolin Tumpach
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Surekha Tennakoon
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Megan Crane
National Centre for Infections in Cancer, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia
David J. Price
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
Sabine Braat
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
Hugh Mason
Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia
Michael Roche
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Angela D.M. Kashuba
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
Peter A. Revill
Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia
Jennifer Audsley
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Sharon R. Lewin
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; Corresponding author. Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 786-798 Elizabeth Street, Melbourne, Victoria 3010, Australia.
Summary: 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.
