Collora Jack A, Steinhauser Savannah F, Davenport Timothy C, Lin Daniel C, Eshetu Amare, Zeidi Samana, Kim Rachel, Frank Cynthia, Kluger Yuval, Springer Sandra A, Ho Ya-Chi
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519, USA.
Division of Infectious Diseases, Department of Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
Cell Rep Med. 2025 Jun 17;6(6):102159. doi: 10.1016/j.xcrm.2025.102159. Epub 2025 Jun 2.
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.
感染艾滋病毒者（PLWHs）患阿片类药物使用障碍（OUD）的风险更高。用于治疗阿片类药物使用障碍的药物（MOUDs）是否会改变艾滋病毒感染中的免疫反应尚不清楚。我们研究了开始使用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及之后3个月的PLWHs的免疫特征。使用单细胞DOGMA-seq，我们对12名PLWHs的29462个外周血免疫细胞进行了分析。我们发现，纳曲酮治疗增加了I型干扰素（IFN）反应，而丁丙诺啡增加了细胞毒性T细胞群体中的肿瘤坏死因子（TNF）反应。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。我们发现有趋势表明，美沙酮治疗后HIV RNA表达增加，而丁丙诺啡和纳曲酮治疗后HIV RNA表达下降。总体而言，接受MOUD治疗的PLWHs免疫反应得到改善，HIV表达降低。
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