Dataset Information

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

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.

SUBMITTER: Zerbato JM

PROVIDER: S-EPMC9763386 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Zerbato Jennifer M JM Avihingsanon Anchalee A Singh Kasha P KP Zhao Wei W Deleage Claire C Rosen Elias E Cottrell Mackenzie L ML Rhodes Ajantha A Dantanarayana Ashanti A Tumpach Carolin C Tennakoon Surekha S Crane Megan M Price David J DJ Braat Sabine S Mason Hugh H Roche Michael M Kashuba Angela D M ADM Revill Peter A PA Audsley Jennifer J Lewin Sharon R SR

EBioMedicine 20221208

<h4>Background</h4>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.<h4>Methods</h4>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 persis ...[more]

PMID: 36502576

Similar Datasets

Project description:BackgroundIn 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.MethodsIn 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.Findings67 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]).InterpretationProgression 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.FundingThis 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.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

Similar Datasets

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