CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study
CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study
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DOI：
10.1007/s13365-017-0600-6
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发表时间：
2018-02-01
影响因子：
3.2
通讯作者：
Gazzard, B.
中科院分区：
文献类型：
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作者：
Barber, T. J.;Imaz, A.;Gazzard, B.
CINAMMON是一项IV期、开放标签、单组、初步研究，在病毒学抑制的HIV感染受试者中评估马拉韦罗（MVC）与地瑞那韦/利托那韦单药治疗（DRV/r）联合使用时对中枢神经系统（CNS）的影响。招募了接受DRV/r的CCR 5热带受试者。受试者保持DRV/r 12周（w）（对照期）。第12 - 36周（干预阶段）添加MVC 150 mg qd。计划在基线、第12周和第36周进行腰椎穿刺（LP）和神经认知功能（Cogstate）检查;第12周前进行MRI，第36周再次进行MRI。主要终点是干预阶段CSF炎症标志物的变化。次要终点包括NC功能和MRI参数的变化。在第12周和第36周测量CSF/血浆DRV/r浓度，在第36周测量MVC。招募了19例患者，15例完成（17例男性，2例女性）。脱落：头痛（2），膝盖问题（无法参加，1），个人原因（1）。平均年龄（范围）45.4岁（27.2-65.1岁），13/19例白色，10/19例MSM。在第12 - 36周未观察到选定CSF标志物的变化。总体NC功能在w12-w36没有改善：总年龄校正z评分改善0.27（加权配对t检验; p = 0.11）;仅对于执行功能，年龄校正z评分改善0.54（p = 0.03）。MRI脑部参数不变。第12周（132）和第36周（112; p = 0.577，Wilcoxon符号秩检验）之间DRV血浆：CSF浓度比不变。第36周时，MVC血浆：CSF浓度比为35。未观察到神经炎症标志物变化。在这项小型研究中，在稳定的DRV/r单药治疗基础上增加24周MVC 150 mg qd，显示执行功能可能改善，无总体NC效应。不能排除学习效果。这一效果应进一步评估。
CINAMMON is a phase IV, open-label, single-arm, pilot study assessing maraviroc (MVC) in the central nervous system (CNS) when added to darunavir/ritonavir monotherapy (DRV/r) in virologically suppressed HIV-infected subjects. CCR5 tropic participants on DRV/r were recruited. Participants remained on DRV/r for 12 week (w) (control phase). MVC 150 mg qd was added w12-w36 (intervention phase). Lumbar puncture (LP) and neurocognitive function (Cogstate) examinations scheduled at baseline, w12 and w36; MRI before w12, again at w36. Primary endpoint was CSF inflammatory marker changes during intervention phase. Secondary endpoints included changes in NC function and MRI parameters. CSF/plasma DRV/r concentrations measured at w12 and w36, MVC at w36. Nineteen patients recruited, 15 completed (17M, 2F). Dropouts: headache (2), knee problem (could not attend, 1), personal reasons (1). Mean age (range) 45.4 years (27.2-65.1), 13/19 white, 10/19 MSM. No changes in selected CSF markers were seen w12-w36. Overall NC function did not improve w12-w36: total age adjusted z score improved by 0.27 (weighted paired t test; p = 0.11); for executive function only, age adjusted z score improved by 0.54 (p = 0.03). MRI brain parameters unchanged. DRV plasma:CSF concentration ratio unchanged between w12 (132) and w36 (112; p = 0.577, Wilcoxon signed-rank). MVC plasma:CSF concentration ratio was 35 at w36. No changes in neuroinflammatory markers seen. In this small study, addition of 24w MVC 150 mg qd to stable DRV/r monotherapy showed possible improvement in executive function with no global NC effect. Learning effect cannot be excluded. This effect should be further evaluated.