Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA 30308.
Department of Biostatistics, Emory University School of Public Health, 1518 Clifton Road, Atlanta, GA 30322.
J Neuroimmunol. 2021 Apr 15;353:577493. doi: 10.1016/j.jneuroim.2021.577493. Epub 2021 Jan 21.
Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514 pg/ml versus median 317 pg/ml, p = 0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5 ng/ml versus median 7.6 ng/ml, p = 0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p = 0.038) and plasma HIV detectability (p = 0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.
需要 HIV 中枢神经系统 (CNS) 持续存在的替代标志物,因为从 CNS 直接测量 HIV 需要专门的方案,而且并不总是可检测或可量化的。我们分析了接受抑制性治疗 (ART) 的 HIV 感染者 (PWH) 的配对血浆和 CSF 样本,这些样本使用经过验证的 HIV 单拷贝 RNA 检测。测量了两种潜在的 CNS 持续存在的标志物 (CXCL10 和 sCD30)。然后,我们在单变量和多变量分析中检查了它们与 CSF HIV RNA 阳性的关联。在 66 名个体中,18.2%的个体 CSF 中可检测到 HIV。CSF 中 HIV 可检测的个体 CSF 中 CXCL10 浓度更高(中位数 514 pg/ml 与中位数 317 pg/ml,p = 0.019),但 CSF sCD30 浓度没有显著差异(中位数 7.5 ng/ml 与中位数 7.6 ng/ml,p = 0.78)。在多变量逻辑分析中,较高的 CSF CXCL10(p = 0.038)和血浆 HIV 可检测性(p = 0.035)均与 CSF HIV 可检测显著相关。sCD30 和 CXCL10 与神经元标志物 NfL 和 NSE 均呈正相关。这项研究表明,尽管在 ART 治疗下病毒学得到抑制,但 CSF CXCL10 浓度反映了低水平的 HIV CNS 持续存在。鉴于它易于检测和定量,这种趋化因子可能是评估针对 CNS 的 HIV 清除疗法的有前途的生物标志物。