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  1. Article ; Online: Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy.

    Singh, Kasha P / Avihingsanon, Anchalee / Zerbato, Jennifer M / Zhao, Wei / Braat, Sabine / Tennakoon, Surekha / Rhodes, Ajantha / Matthews, Gail V / Fairley, Christopher K / Sasadeusz, Joe / Crane, Megan / Audsley, Jennifer / Lewin, Sharon R

    EBioMedicine

    2024  Volume 102, Page(s) 105054

    Abstract: Background: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial ... ...

    Abstract Background: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation.
    Methods: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time.
    Findings: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4 ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]).
    Interpretation: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART.
    Funding: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.
    MeSH term(s) Adult ; Humans ; Male ; Middle Aged ; Female ; Hepatitis B virus ; Coinfection ; HIV Infections/complications ; HIV Infections/drug therapy ; Liver Cirrhosis/complications ; Liver Cirrhosis/diagnosis ; Disease Progression ; CD4 Lymphocyte Count
    Language English
    Publishing date 2024-03-21
    Publishing country Netherlands
    Document type Observational Study ; Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2024.105054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Markers of Immune Activation and Inflammation Are Associated with Higher Levels of Genetically-Intact HIV in HIV-HBV Co-Infected Individuals.

    Wang, Xiao Qian / Zerbato, Jennifer M / Avihingsanon, Anchalee / Fisher, Katie / Schlub, Timothy / Rhodes, Ajantha / Audsley, Jennifer / Singh, Kasha P / Zhao, Wei / Lewin, Sharon R / Palmer, Sarah

    Journal of virology

    2022  Volume 96, Issue 16, Page(s) e0058822

    Abstract: Co-infection with hepatitis B (HBV) and human immunodeficiency virus (HIV) increases overall and liver-related mortality. In order to identify interactions between these two ... ...

    Abstract Co-infection with hepatitis B (HBV) and human immunodeficiency virus (HIV) increases overall and liver-related mortality. In order to identify interactions between these two viruses
    MeSH term(s) Coinfection/pathology ; Coinfection/virology ; DNA, Viral/genetics ; HIV Infections/complications ; HIV Infections/pathology ; HIV Infections/virology ; Hepatitis B/complications ; Hepatitis B/pathology ; Hepatitis B/virology ; Hepatitis B virus/physiology ; Humans ; Inflammation/virology ; Proviruses/genetics ; Thailand/epidemiology ; Viremia/virology
    Chemical Substances DNA, Viral
    Language English
    Publishing date 2022-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00588-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 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

    EBioMedicine, Vol 87, Iss , Pp 104391- (2023)

    1480  

    Abstract: 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. ... ...

    Abstract 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.
    Keywords HIV-HBV co-infection ; Liver biopsy ; Hepatocytes ; HIV reservoir ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy.

    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

    EBioMedicine

    2022  Volume 87, Page(s) 104391

    Abstract: 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.: ... ...

    Abstract 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.
    MeSH term(s) Humans ; Prospective Studies ; Coinfection ; Thailand ; Hepatitis B/complications ; HIV Infections/complications ; HIV Infections/drug therapy ; Hepatitis B virus/genetics ; Anti-Retroviral Agents/pharmacology ; Anti-Retroviral Agents/therapeutic use ; DNA, Viral/genetics ; Hepatocytes
    Chemical Substances Anti-Retroviral Agents ; DNA, Viral
    Language English
    Publishing date 2022-12-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Temporal differences in culturable severe acute respiratory coronavirus virus 2 (SARS-CoV-2) from the respiratory and gastrointestinal tracts in a patient with moderate coronavirus disease 2019 (COVID-19).

    Audsley, Jennifer M / Holmes, Natasha E / Mordant, Francesca L / Douros, Celia / Zufan, Sara E / Nguyen, Thi H O / Kedzierski, Lukasz / Rowntree, Louise C / Hensen, Luca / Subbarao, Kanta / Kedzierska, Katherine / Nicholson, Suellen / Sherry, Norelle / Thevarajan, Irani / Tran, Thomas / Druce, Julian

    Infection control and hospital epidemiology

    2021  Volume 43, Issue 9, Page(s) 1286–1288

    MeSH term(s) COVID-19 ; Gastrointestinal Tract ; Humans ; Middle East Respiratory Syndrome Coronavirus ; SARS-CoV-2 ; Virus Diseases
    Language English
    Publishing date 2021-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639378-0
    ISSN 1559-6834 ; 0195-9417 ; 0899-823X
    ISSN (online) 1559-6834
    ISSN 0195-9417 ; 0899-823X
    DOI 10.1017/ice.2021.223
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

    Wang, Ya / Schughart, Klaus / Pelaia, Tiana Maria / Chew, Tracy / Kim, Karan / Karvunidis, Thomas / Knippenberg, Ben / Teoh, Sally / Phu, Amy L / Short, Kirsty R / Iredell, Jonathan / Thevarajan, Irani / Audsley, Jennifer / Macdonald, Stephen / Burcham, Jonathon / Predict-Consortium / Tang, Benjamin / McLean, Anthony / Shojaei, Maryam

    International journal of molecular sciences

    2023  Volume 24, Issue 3

    Abstract: Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease ... ...

    Abstract Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (
    MeSH term(s) Humans ; COVID-19 ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 9/metabolism ; Signal Transduction ; Intercellular Signaling Peptides and Proteins ; Mitochondria/metabolism
    Chemical Substances Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Intercellular Signaling Peptides and Proteins ; MMP9 protein, human (EC 3.4.24.35)
    Language English
    Publishing date 2023-01-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24032524
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  7. Article ; Online: Blood transcriptome responses in patients correlate with severity of COVID-19 disease.

    Wang, Ya / Schughart, Klaus / Pelaia, Tiana Maria / Chew, Tracy / Kim, Karan / Karvunidis, Thomas / Knippenberg, Ben / Teoh, Sally / Phu, Amy L / Short, Kirsty R / Iredell, Jonathan / Thevarajan, Irani / Audsley, Jennifer / Macdonald, Stephen / Burcham, Jonathon / McLean, Anthony / Tang, Benjamin / Shojaei, Maryam

    Frontiers in immunology

    2023  Volume 13, Page(s) 1043219

    Abstract: Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health ... ...

    Abstract Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state.
    Aim: Our current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants.
    Results: All WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways.
    Conclusions: Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.
    MeSH term(s) Humans ; COVID-19/genetics ; Transcriptome ; SARS-CoV-2 ; Gene Expression Profiling ; Neutrophils
    Language English
    Publishing date 2023-01-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1043219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Cell-based influenza vaccines: progress to date.

    Audsley, Jennifer M / Tannock, Gregory A

    Drugs

    2008  Volume 68, Issue 11, Page(s) 1483–1491

    Abstract: Human vaccines against influenza have been available for almost 60 years and, until recently, were prepared almost entirely from viruses grown in the allantoic cavity of 9- to 11-day-old embryonated chicken eggs. Manufacture involving eggs is not ... ...

    Abstract Human vaccines against influenza have been available for almost 60 years and, until recently, were prepared almost entirely from viruses grown in the allantoic cavity of 9- to 11-day-old embryonated chicken eggs. Manufacture involving eggs is not sufficiently flexible to allow vaccine supplies to be rapidly expanded, especially in the face of an impending pandemic. Other problems may arise from the infections of progenitor flocks that adversely affect egg supplies, and from the manufacturing process itself, where breakdowns in sterility can occur from the occasional contamination of large batches of viral allantoic fluid. In addition, egg-grown viruses exhibit differences in antigenicity from viruses isolated in mammalian cell lines from clinical specimens. These concerns and the probable need for greatly expanded manufacturing capability in the future have been brought into focus in recent years by the limited spread of H5N1 avian influenza infections to humans in several Asian countries. Alternative approaches involving the use of accredited anchorage-dependent and -independent preparations of the African Green monkey kidney (Vero), Madin-Darby canine kidney (MDCK) and other cell lines have been pursued by several manufacturers in recent years. Yields comparable with those obtained in embryonated eggs have been achieved. These improvements have occurred in parallel with newer technologies that allow the growth of cells in newer synthetic media that do not contain animal serum, in order to allay the concerns of regulators about the potential for spread of transmissible spongiform encephalopathies.
    MeSH term(s) Animals ; Cells, Cultured ; Disease Outbreaks ; Humans ; Influenza A virus/immunology ; Influenza A virus/isolation & purification ; Influenza B virus/immunology ; Influenza B virus/isolation & purification ; Influenza Vaccines/economics ; Influenza, Human/epidemiology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Vaccines, Synthetic/economics
    Chemical Substances Influenza Vaccines ; Vaccines, Synthetic
    Language English
    Publishing date 2008-07-16
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.2165/00003495-200868110-00002
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  9. Article ; Online: Intrahepatic CXCL10 is strongly associated with liver fibrosis in HIV-Hepatitis B co-infection.

    Singh, Kasha P / Zerbato, Jennifer M / Zhao, Wei / Braat, Sabine / Deleage, Claire / Tennakoon, G Surekha / Mason, Hugh / Dantanarayana, Ashanti / Rhodes, Ajantha / Rhodes, Jake W / Torresi, Joe / Harman, Andrew N / Revill, Peter A / Crane, Megan / Estes, Jacob D / Avihingsanon, Anchalee / Lewin, Sharon R / Audsley, Jennifer

    PLoS pathogens

    2020  Volume 16, Issue 9, Page(s) e1008744

    Abstract: In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine ... ...

    Abstract In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine whether liver disease was associated with intrahepatic or circulating markers of inflammation or burden of HIV or HBV, liver biopsies and blood were collected from HIV-HBV co-infected individuals (n = 39) living in Bangkok, Thailand and naïve to ART. Transient elastography (TE) was performed. Intrahepatic and circulating markers of inflammation and microbial translocation were quantified by ELISA and bead arrays and HIV and HBV infection quantified by PCR. Liver fibrosis (measured by both transient elastography and liver biopsy) was statistically significantly associated with intrahepatic mRNA for CXCL10 and CXCR3 using linear and logistic regression analyses adjusted for CD4 T-cell count. There was no evidence of a relationship between liver fibrosis and circulating HBV DNA, qHBsAg, plasma HIV RNA or circulating cell-associated HIV RNA or DNA. Using immunohistochemistry of liver biopsies from this cohort, intrahepatic CXCL10 was detected in hepatocytes associated with inflammatory liver infiltrates in the portal tracts. In an in vitro model, we infected an HBV-infected hepatocyte cell line with HIV, followed by interferon-γ stimulation. HBV-infected cells lines produced significantly more CXCL10 than uninfected cells lines and this significantly increased in the presence of an increasing multiplicity of HIV infection. Conclusion: Enhanced production of CXCL10 following co-infection of hepatocytes with both HIV and HBV may contribute to accelerated liver disease in the setting of HIV-HBV co-infection.
    MeSH term(s) Adult ; Australia/epidemiology ; Chemokine CXCL10/metabolism ; Cohort Studies ; Coinfection/complications ; Coinfection/virology ; Female ; HIV/isolation & purification ; HIV Infections/complications ; HIV Infections/virology ; Hepatitis B/complications ; Hepatitis B/virology ; Hepatitis B virus/isolation & purification ; Humans ; Incidence ; Liver Cirrhosis/epidemiology ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/virology ; Male ; Netherlands/epidemiology ; Prognosis ; Thailand/epidemiology
    Chemical Substances CXCL10 protein, human ; Chemokine CXCL10
    Language English
    Publishing date 2020-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1008744
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  10. Article ; Online: Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection-Lessons for Functional HBV Cure?

    Audsley, Jennifer / Avihingsanon, Anchalee / Littlejohn, Margaret / Bowden, Scott / Matthews, Gail V / Fairley, Christopher K / Lewin, Sharon R / Sasadeusz, Joe

    Journal of acquired immune deficiency syndromes (1999)

    2020  Volume 84, Issue 5, Page(s) 527–533

    Abstract: Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated ... ...

    Abstract Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection.
    Methods: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years.
    Results: 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL).
    Conclusions: HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure.
    MeSH term(s) Anti-HIV Agents/therapeutic use ; Australia/epidemiology ; Coinfection/virology ; DNA, Viral/isolation & purification ; Drug Administration Schedule ; HIV Infections/complications ; HIV Infections/epidemiology ; HIV-1 ; Hepatitis B Surface Antigens/blood ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/epidemiology ; Humans ; RNA, Viral/isolation & purification ; Tenofovir/administration & dosage ; Tenofovir/therapeutic use ; Thailand/epidemiology
    Chemical Substances Anti-HIV Agents ; DNA, Viral ; Hepatitis B Surface Antigens ; RNA, Viral ; Tenofovir (99YXE507IL)
    Language English
    Publishing date 2020-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 0897-5965 ; 0894-9255 ; 1525-4135
    DOI 10.1097/QAI.0000000000002386
    Database MEDical Literature Analysis and Retrieval System OnLINE

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