Tiraboschi J M, Muñoz-Moreno J A, Puertas M C, Alonso-Villaverde C, Prats A, Ferrer E, Rozas N, Maso M, Ouchi D, Martinez-Picado J, Podzamczer D
Bellvitge University Hospital, Barcelona, Spain.
IDIBELL, Barcelona, Spain.
HIV Med. 2015 Jul;16(6):388-92. doi: 10.1111/hiv.12243. Epub 2015 Feb 27.
The aim of the study was to evaluate HIV-1 viral load (VL) and inflammatory markers in cerebrospinal fluid (CSF) and neurocognitive performance in patients with neurocognitive impairment (NCI) while they were receiving tenofovir (TDF)/ emtricitabine (FTC)/efavirenz (EFV) and after switching to a regimen with enhanced central nervous system (CNS) penetrability.
This was a prospective, single-arm pilot study. HIV-1-infected patients with plasma viral suppression and HIV-associated NCI on a regimen including TDF/FTC/EFV were switched to abacavir (ABC)/lamivudine (3TC)/maraviroc (MVC). The Global Deficit Score (GDS) was used to score cognitive function at baseline and 48 weeks after treatment switch. Both CSF and blood samples were taken at baseline and between weeks 24 and 36 after switching. HIV-1 RNA in plasma and CSF was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Inflammatory biomarkers in CSF were measured by enzyme-linked immunosorbent assay (ELISA).
A total of 71 patients receiving TDF/FTC/EFV were screened. Twelve of them (17%) had documented NCI, lacked the human leucocyte antigen (HLA)-B*57:01 haplotype and harboured Chemokine Receptor Type-5 (CCR5)-tropic virus. Eight patients had detectable HIV-1 RNA (between 2.7 and 41.6 HIV-1 RNA copies/mL) in CSF at baseline. All participants had elevated levels of neopterin and Monocyte Chemoattractant Protein 1 (MCP-1) in CSF at baseline. Eight out of 12 patients completed their follow-up assessment after treatment switch. The GDS decreased from 0.55 to 0.4 (P = 0.085). Median HIV-1 RNA in CSF decreased from 3.49 to 2.20 (P = 0.23). Among the inflammation markers in CSF, tumour necrosis factor (TNF)-α decreased significantly from median 0.51 to 0.35 pg/mL (P = 0.027), showing a correlation with the changes in neopterin, interferon (IFN)-γ and interleukin (IL)-6.
Most patients with NCI receiving TDF/FTC/EFV had low-level viraemia and/or increased inflammatory markers in CSF. Treatment switching to an MVC-containing regimen with better CNS penetration resulted in a trend towards improvement in neurocognitive status and reduced TNF-α concentrations in CSF.
本研究旨在评估接受替诺福韦（TDF）/恩曲他滨（FTC）/依非韦伦（EFV）治疗的神经认知障碍（NCI）患者脑脊液（CSF）中的HIV-1病毒载量（VL）和炎症标志物，以及神经认知功能，同时评估改用具有增强的中枢神经系统（CNS）渗透性的治疗方案后的情况。
这是一项前瞻性单臂试点研究。将血浆病毒得到抑制且接受包含TDF/FTC/EFV方案治疗的HIV-1感染的NCI患者换用阿巴卡韦（ABC）/拉米夫定（3TC）/马拉维罗（MVC）。使用全球缺陷评分（GDS）在基线和治疗转换后48周对认知功能进行评分。在基线以及转换治疗后第24周和第36周之间采集CSF和血液样本。通过定量逆转录聚合酶链反应（qRT-PCR）测定血浆和CSF中的HIV-1 RNA。通过酶联免疫吸附测定（ELISA）测量CSF中的炎症生物标志物。
共筛查了71例接受TDF/FTC/EFV治疗的患者。其中12例（17%）有记录的NCI，缺乏人类白细胞抗原（HLA）-B*57:01单倍型且携带C趋化因子受体5型（CCR5）嗜性病毒。8例患者在基线时CSF中可检测到HIV-1 RNA（2.7至41.6个HIV-1 RNA拷贝/mL）。所有参与者在基线时CSF中的新蝶呤和单核细胞趋化蛋白1（MCP-1）水平均升高。12例患者中有8例在治疗转换后完成了随访评估。GDS从0.55降至0.4（P = 0.085）。CSF中HIV-1 RNA中位数从3.49降至2.20（P = 0.23）。在CSF中的炎症标志物中，肿瘤坏死因子（TNF）-α中位数从0.51 pg/mL显著降至0.35 pg/mL（P = 0.027），与新蝶呤、干扰素（IFN）-γ和白细胞介素（IL）-6的变化相关。
大多数接受TDF/FTC/EFV治疗的NCI患者CSF中有低水平病毒血症和/或炎症标志物升高。改用具有更好CNS渗透性的含MVC方案治疗导致神经认知状态有改善趋势，且CSF中TNF-α浓度降低。
