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

• Published in: EBioMedicine 2023-01, Vol.87, p.104391-104391, Article 104391
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Anti-Retroviral Agents - pharmacology; Anti-Retroviral Agents - therapeutic use; Coinfection; DNA, Viral - genetics; Hepatitis B - complications; Hepatitis B virus - genetics; Hepatocytes; HIV Infections - complications; HIV Infections - drug therapy; HIV reservoir; HIV-HBV co-infection; Humans; Liver biopsy; Prospective Studies; Thailand
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2022.104391

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. 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. 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. Persistence of HIV DNA in liver in PWH on ART represents an additional reservoir that warrants further investigation. 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.