Jasmini Alagaratnam , Wolfgang Stöhr , Elizabeth Hamlyn , Kholoud Porter , Jamie Toombs , Amanda Heslegrave , Henrik Zetterberg , Magnus Gisslén , Jonathan Underwood , Mauro Schechter , Pontiano Kaleebu , Giuseppe Tambussi , Sabine Kinloch , Jose M. Miro , Anthony D. Kelleher , Abdel Babiker , John Frater , Alan Winston , Sarah Fidler , The SPARTAC Trial Investigators
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We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA).</p></div><div><h3>Design</h3><p>Retrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption.</p></div><div><h3>Methods</h3><p>NfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4<sup>+</sup> T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression.</p></div><div><h3>Results</h3><p>NfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log<sub>10</sub> copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51).</p></div><div><h3>Conclusions</h3><p>Using plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.</p></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 2","pages":"Article 100381"},"PeriodicalIF":3.5000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2055664024000189/pdfft?md5=e27b2f871c80de05181d324e7dfff871&pid=1-s2.0-S2055664024000189-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial\",\"authors\":\"Jasmini Alagaratnam , Wolfgang Stöhr , Elizabeth Hamlyn , Kholoud Porter , Jamie Toombs , Amanda Heslegrave , Henrik Zetterberg , Magnus Gisslén , Jonathan Underwood , Mauro Schechter , Pontiano Kaleebu , Giuseppe Tambussi , Sabine Kinloch , Jose M. 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We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA).</p></div><div><h3>Design</h3><p>Retrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption.</p></div><div><h3>Methods</h3><p>NfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4<sup>+</sup> T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression.</p></div><div><h3>Results</h3><p>NfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log<sub>10</sub> copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51).</p></div><div><h3>Conclusions</h3><p>Using plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.</p></div>\",\"PeriodicalId\":17552,\"journal\":{\"name\":\"Journal of Virus Eradication\",\"volume\":\"10 2\",\"pages\":\"Article 100381\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2055664024000189/pdfft?md5=e27b2f871c80de05181d324e7dfff871&pid=1-s2.0-S2055664024000189-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Virus Eradication\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2055664024000189\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Virus Eradication","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2055664024000189","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的抗逆转录病毒疗法（ART）对 HIV 复制的抑制可限制神经元损伤和炎症。抗逆转录病毒疗法的中断在 HIV 治愈试验中测试疗效，而抗逆转录病毒疗法中断后的病毒反弹可能会诱发神经元损伤。我们研究了在 HIV-1 原发感染（PHI）期间开始的方案定义的抗逆转录病毒疗法中断对神经轴突损伤生物标志物（神经丝光蛋白（NfL））的影响，及其与炎症（D-二聚体和白细胞介素-6（IL-6））和 HIV-1 储库规模（HIV-1 DNA 总量）的关联。方法在接受抗逆转录病毒疗法前、接受抗逆转录病毒疗法 48 周后和停止接受抗逆转录病毒疗法 12 周后测量 NfL（Simoa 免疫测定，Quanterix™）。部分参与者的血浆 D-二聚体和 IL-6 以及外周 CD4+ T 细胞中的 HIV-1 DNA 总含量也得到了检测结果。使用混合模型评估了NfL的纵向变化，并使用线性回归评估了NfL与临床和实验室参数的关联。结果NfL在48周抗逆转录病毒疗法后有所下降（几何平均数从6.9 pg/mL降至5.8 pg/mL，p = 0.006），尽管大多数参与者的病毒反弹（中位数为1.7至3.9血浆HIV-1 RNA log10拷贝数/mL），但在停止抗逆转录病毒疗法后的12周内没有进一步的显著变化。较高的基线 NfL 与较高的血浆 HIV-1 RNA（p = 0.020）和较大的年龄（p = 0.002）独立相关。结论 使用血浆 NfL 作为替代标志物，在 PHI 期间开始接受抗逆转录病毒疗法的一组参与者中观察到神经轴损伤有所减轻，尽管大多数参与者的病毒反弹，但在中断抗逆转录病毒疗法长达 12 周后，没有证据表明神经轴损伤反弹。
Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial
Objective
Antiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA).
Design
Retrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption.
Methods
NfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4+ T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression.
Results
NfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log10 copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51).
Conclusions
Using plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.
期刊介绍：
The Journal of Virus Eradication aims to provide a specialist, open-access forum to publish work in the rapidly developing field of virus eradication. The Journal covers all human viruses, in the context of new therapeutic strategies, as well as societal eradication of viral infections with preventive interventions.
The Journal is aimed at the international community involved in the prevention and management of viral infections. It provides an academic forum for the publication of original research into viral reservoirs, viral persistence and virus eradication and ultimately development of cures.
The Journal not only publishes original research, but provides an opportunity for opinions, reviews, case studies and comments on the published literature. It focusses on evidence-based medicine as the major thrust in the successful management of viral infections.The Journal encompasses virological, immunological, epidemiological, modelling, pharmacological, pre-clinical and in vitro, as well as clinical, data including but not limited to drugs, immunotherapy and gene therapy. It is an important source of information on the development of vaccine programs and preventative measures aimed at virus eradication.
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