抗逆转录病毒治疗期间脑脊液中持续性HIV-1 RNA的患病率及其相关因素

Prevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy.

作者信息

Anderson Albert M, Muñoz-Moreno Jose A, McClernon Daniel R, Ellis Ronald J, Cookson Debra, Clifford David B, Collier Ann C, Gelman Benjamin B, Marra Christina M, McArthur Justin C, McCutchan J Allen, Morgello Susan, Sacktor Ned, Simpson David M, Franklin Donald R, Heaton Robert K, Grant Igor, Letendre Scott L

机构信息

Emory University School of Medicine, Atlanta, Georgia.

Germans Trias i Pujol University Hospital, Barcelona, Spain.

出版信息

J Infect Dis. 2017 Jan 1;215(1):105-113. doi: 10.1093/infdis/jiw505. Epub 2016 Oct 26.

Abstract

BACKGROUND

Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).

METHODS

Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.

RESULTS

HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4 T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.

CONCLUSIONS

Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4 T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.

摘要

背景

神经认知障碍在人类免疫缺陷病毒(HIV)阳性成年人中仍然很常见,这可能归因于抗逆转录病毒治疗(ART)期间脑脊液(CSF)中持续存在的HIV-1 RNA。

方法

我们使用单拷贝检测法,测量了220名接受抑制性ART的HIV阳性成年人的脑脊液和血浆样本中的HIV-1 RNA水平。55名参与者接受了两次检测。

结果

在42.3%的脑脊液样本和65.2%的血浆样本中检测到了HIV-1 RNA。脑脊液中HIV-1 RNA水平较高的相关因素包括更低的最低点和当前CD4 T细胞计数、血浆HIV-1 RNA水平≥1拷贝/毫升,以及更低的中枢神经系统渗透效率评分(模型P<.001)。神经认知功能较差与血浆和脑脊液中HIV-1 RNA检测结果不一致、脑脊液中总体HIV-1 RNA水平较低以及ART持续时间较长等因素有关(模型P<.001)。在纵向亚组中,大多数参与者(69%)的脑脊液HIV-1 RNA在7个月内持续存在。

结论

在抑制性ART期间,脑脊液中低水平的HIV-1 RNA很常见,并且与血液中低水平的HIV-1 RNA、更好的免疫状态以及更低的ART药物在脑脊液中的分布有关。HIV-1 RNA不一致与HIV相关神经认知障碍(HAND)之间的关联可能反映了区室化。HAND、脑脊液中较低的HIV-1 RNA水平和较低的CD4 T细胞计数之间的关系可能反映了中枢神经系统对HIV-1免疫反应的紊乱。

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