Liu Qian, Tao Wendan, Yang Honghong, Wu Yushan, Yu Qing, Liu Min
Department of Infectious Disease, Chongqing Public Health Medical Center, Chongqing 400036, China.
Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China.
Brain Sci. 2022 Jun 16;12(6):791. doi: 10.3390/brainsci12060791.
Cerebrospinal fluid (CSF) human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) at higher levels than in plasma has been observed in HIV-1-positive patients and defined as CSF/plasma discordance or CSF escape. Discordance is particularly seen in untreated patients with antiretroviral agents. Quantitative data regarding its association with blood−brain barrier (BBB) damage and intracranial co-infection with other pathogens are limited. Therefore, we used the CSF to plasma HIV-1 RNA ratio (HRR) to determine its relation to central nervous system (CNS) co-infection in HIV-1-positive treatment-naïve individuals. We retrospectively recruited the subjects with HIV-1-positive and potential neurological deficits. A lumbar puncture was performed before the antiretroviral therapy. The paired CSF/plasma HIV-1 RNA samples were analyzed. Univariate and multivariate logistic regression models and multiple spine regression analyses were performed to assess the association between the HRR and CNS co-infection. A total of 195 patients with 78% males (median age: 49 years) were included in this study, of whom 98 (50.2%) had CNS co-infection with other pathogens. The receiver-operating characteristic curve analysis showed that the optimal cutoff value for the HRR to predict the CNS co-infection was 1.00. Higher HRR (≥1) was significantly associated with tuberculous meningitis (OR 6.50, 95% CI 2.08−20.25, p = 0.001), cryptococcus meningitis (OR 7.58, 95% CI 2.10−27.32, p = 0.001), and multiple co-infection (OR 4.04, 95% CI 1.02−16.04, p = 0.047). Higher HRR (≥1) (OR 3.01, 95% CI 1.09−8.73, p = 0.032) was independently associated with the CNS co-infection after adjusting for covariates. No significant nonlinear association was found between the HRR and CNS co-infection in the multivariate spline regression (p > 0.05) and a positive relationship was found between the HRR and CNS co-infection when the HRR was ≥0.78. Higher HRR was associated with an increased risk of CNS co-infection in HIV-1-positive patients. The relationship between the HRR and CNS co-infection may be related to the BBB disturbance and warrants further investigation with a large, longitudinal cohort.
在HIV-1阳性患者中，观察到脑脊液（CSF）中的人类免疫缺陷病毒1型（HIV-1）核糖核酸（RNA）水平高于血浆中的水平，这被定义为脑脊液/血浆不一致或脑脊液逃逸。不一致现象在未接受抗逆转录病毒药物治疗的患者中尤为常见。关于其与血脑屏障（BBB）损伤及与其他病原体颅内合并感染之间关联的定量数据有限。因此，我们使用脑脊液与血浆HIV-1 RNA比值（HRR）来确定其与未接受过治疗的HIV-1阳性个体中枢神经系统（CNS）合并感染的关系。我们回顾性招募了HIV-1阳性且有潜在神经功能缺损的受试者。在抗逆转录病毒治疗前进行腰椎穿刺。对配对的脑脊液/血浆HIV-1 RNA样本进行分析。进行单因素和多因素逻辑回归模型以及多元样条回归分析，以评估HRR与CNS合并感染之间的关联。本研究共纳入195例患者，其中男性占78%（中位年龄：49岁），98例（50.2%）患者存在CNS与其他病原体的合并感染。受试者工作特征曲线分析表明，预测CNS合并感染的HRR最佳截断值为1.00。较高的HRR（≥1）与结核性脑膜炎（比值比6.50，95%置信区间2.08 - 20.25，p = 0.001）、隐球菌性脑膜炎（比值比7.58，95%置信区间2.10 - 27.32，p = 0.001）以及多重合并感染（比值比4.04，95%置信区间1.02 - 16.04，p = 0.047）显著相关。在调整协变量后，较高的HRR（≥1）（比值比3.01，95%置信区间1.09 - 8.73，p = 0.032）与CNS合并感染独立相关。在多元样条回归中，未发现HRR与CNS合并感染之间存在显著的非线性关联（p > 0.05），当HRR≥0.78时，发现HRR与CNS合并感染呈正相关。较高的HRR与HIV-1阳性患者CNS合并感染风险增加相关。HRR与CNS合并感染之间的关系可能与血脑屏障紊乱有关，值得通过大型纵向队列进一步研究。
