Medications for opioid use disorder shape immune responses during chronic HIV infection.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-06-17 Epub Date: 2025-06-02 DOI:10.1016/j.xcrm.2025.102159

Jack A Collora, Savannah F Steinhauser, Timothy C Davenport, Daniel C Lin, Amare Eshetu, Samana Zeidi, Rachel Kim, Cynthia Frank, Yuval Kluger, Sandra A Springer, Ya-Chi Ho

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Abstract

People living with HIV (PLWHs) have higher risk of opioid use disorder (OUD). Whether medications for opioid use disorder (MOUDs) change immune responses in HIV infection is unknown. We examined the immune profiles in PLWHs before and 3 months after initiation of the μ opioid receptor agonist methadone, partial agonist buprenorphine, and antagonist naltrexone. Using single-cell DOGMA-seq, we profiled 29,462 peripheral blood immune cells in 12 PLWHs. We found that naltrexone treatment increased type I interferon (IFN) responses while buprenorphine increased tumor necrosis factor (TNF) responses in cytotoxic T cell population. We found that HIV+ cells in PLWHs with OUD upregulated PTPN13 and TAF5L, both of which are associated with HIV replication. We found trends suggesting increased HIV RNA expression after methadone and decreased HIV RNA expression after buprenorphine and naltrexone initiation. Overall, PLWHs treated with MOUD had improved immune responses and decreased HIV expression.

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阿片类药物使用障碍影响慢性HIV感染期间的免疫反应。

艾滋病毒感染者（PLWHs）发生阿片类药物使用障碍（OUD）的风险较高。阿片类药物使用障碍（MOUDs）药物是否会改变HIV感染的免疫反应尚不清楚。我们检测了在使用μ阿片受体激动剂美沙酮、部分激动剂丁丙诺啡和拮抗剂纳曲酮之前和3个月后PLWHs的免疫谱。使用单细胞DOGMA-seq，我们分析了12例PLWHs的29,462个外周血免疫细胞。我们发现纳曲酮治疗增加了I型干扰素（IFN）应答，而丁丙诺啡增加了细胞毒性T细胞群中肿瘤坏死因子（TNF）应答。我们发现，患有OUD的PLWHs中的HIV+细胞上调了PTPN13和TAF5L，这两者都与HIV复制有关。我们发现趋势表明，美沙酮起始后HIV RNA表达增加，丁丙诺啡和纳曲酮起始后HIV RNA表达降低。总的来说，用mod治疗的PLWHs免疫应答改善，HIV表达降低。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.