Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
EBioMedicine. 2023 Jan;87:104391. doi: 10.1016/j.ebiom.2022.104391. Epub 2022 Dec 8.
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.
HIV 可感染包括肝细胞、枯否细胞和浸润 T 细胞在内的肝脏中的多种细胞，但在接受抑制性抗逆转录病毒治疗 (ART) 的 HIV 感染者 (PWH) 中，HIV 是否能在肝脏中持续存在仍不清楚。
在泰国曼谷的一项前瞻性纵向 PWH 和乙型肝炎病毒 (HBV) 合并感染队列研究中，我们在接受 ART 治疗之前和之后从 18 名参与者中采集了血液和肝活检，并使用定量 (q)PCR 和 RNA/DNAscope 来量化 HIV 和 HBV 的持续存在。使用质谱法来量化抗逆转录病毒 (ARV) 药物水平。
在 ART 之前进行的肝活检中，通过 qPCR 检测到 53%（17 名参与者中的 9 名）和 47%（17 名参与者中的 8 名）的参与者存在 HIV DNA 和 HIV RNA。在接受中位数为 3.4 年的 ART 治疗后，通过 qPCR、DNAscope 或两者均在 61%（18 名参与者中的 11 名）的参与者的肝中检测到 HIV DNA，但仅在非常低且无法定量的水平。通过免疫组织化学染色，在 ART 时，HIV DNA 存在于肝细胞和肝浸润 CD4+T 细胞中。通过 qPCR 或 RNAscope 均未在 ART 时的肝活检中检测到 HIV RNA。所有 ARV 在肝组织中均清晰可见。
在接受 ART 的 PWH 中，肝内 HIV DNA 的持续存在代表了一个需要进一步研究的额外储存库。
澳大利亚国家卫生与医学研究理事会（项目资助 APP1101836、1149990 和 1135851）；本项目部分资金由美国国立卫生研究院国家癌症研究所提供，合同号为 75N91019D00024。
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