HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy
- Author(s)
- Zerbato, JM; Avihingsanon, A; Singh, KP; Zhao, W; Deleage, C; Rosen, E; Cottrell, ML; Rhodes, A; Dantanarayana, A; Tumpach, C; Tennakoon, S; Crane, M; Price, DJ; Braat, S; Mason, H; Roche, M; Kashuba, ADM; Revill, PA; Audsley, J; Lewin, SR;
- Journal Title
- eBiomedicine
- Publication Type
- Research article
- 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.
- Publisher
- Elsevier
- Keywords
- Humans; Prospective Studies; *Coinfection; Thailand; *Hepatitis B/complications; *HIV Infections/complications/drug therapy; Hepatitis B virus/genetics; Anti-Retroviral Agents/pharmacology/therapeutic use; DNA, Viral/genetics; Hepatocytes; HIV reservoir; HIV-HBV co-infection; Liver biopsy
- Department(s)
- Infectious Diseases
- PubMed ID
- 36502576
- Publisher's Version
- https://doi.org/10.1016/j.ebiom.2022.104391
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ebiom.2022.104391- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-15 07:25:02
Last Modified: 2023-06-15 07:25:48