Department of Neurosciences, University of California, San Diego, San Diego, California, USA.
Monogram Biosciences, South San Francisco, California, USA.
Clin Infect Dis. 2023 Mar 21;76(6):1103-1109. doi: 10.1093/cid/ciac851.
Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH).
Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2.
Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds.
Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
神经丝轻链(NFL)浓度反映轴突损伤,在几种多发性神经病中可见,但尚未在人类免疫缺陷病毒(HIV)远端感觉多发性神经病(DSP)中进行研究。我们评估了来自 2 个独立队列的 HIV 感染者(PWH)和无 HIV 感染者(PWoH)的脑脊液(CSF)和血浆中与 DSP 相关的 NFL。
队列 1 由 CHARTER 研究中的 PWH 组成。队列 2 由 HIV 神经行为研究中心(HNRC)中的 PWH 和 PWoH 组成。我们在两个队列中评估了 DSP 体征和症状。免疫测定法测量了所有 CSF 中的 NFL 和队列 2 中的血浆 NFL。
队列 1 由 111 名 PWH 组成,平均年龄±标准差为 56.8±8.32 岁,15.3%为女性,38.7%为黑人,49.6%为白人,目前 CD4+T 细胞(中位数,四分位距 [IQR])为 532/µL(295,785),83.5%的人血浆 HIV RNA≤50 拷贝/mL。队列 2 由与队列 1 中 PWH 相似的 PWH 组成,但也包括 51 名 PWoH,总年龄为 58.4±6.68 岁,41.2%为女性,18.0%为黑人,西班牙裔、非西班牙裔白人 52.0%,6.0%为白人。在两个 PWH 队列中,有 DSP 体征的 PWH 的 CSF 和血浆 NFL 均显著升高。PWoH 的发现虽不显著,但也相似。观察到的关系不受混杂因素的影响。
PWH 和 PWoH 中均有 DSP 的 CSF 和血浆 NFL 升高。我们的研究结果与其他人的研究结果相吻合,表明 NFL 是反映周围神经损伤的可靠生物标志物。NFL 等生物标志物可能为 HIV DSP 的神经再生策略临床试验提供、验证和优化。