Chelsea and Westminster NHS Foundation Trust and St Stephen's AIDS Trust, 4th Floor, St Stephen's Centre, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
Imperial College London, London, UK.
J Neurovirol. 2018 Feb;24(1):98-105. doi: 10.1007/s13365-017-0600-6. Epub 2017 Dec 26.
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.
CINAMMON 是一项四期、开放性、单臂、初步研究，评估了马拉维若（MVC）在病毒学抑制的 HIV 感染者中添加到达芦那韦/利托那韦单药治疗（DRV/r）时对中枢神经系统（CNS）的影响。招募了 CCR5 嗜性的 DRV/r 参与者。参与者继续接受 DRV/r 治疗 12 周（w）（对照期）。MVC 150mgqd 于 w12-w36 期间添加（干预期）。在基线、w12 和 w36 时安排腰椎穿刺（LP）和神经认知功能（Cogstate）检查；在 w12 之前和 w36 再次进行 MRI。主要终点是干预期间 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 w12 和 w36 时测量 CSF/血浆 DRV/r 浓度，在 w36 时测量 MVC。招募了 19 名患者，15 名完成（17 名男性，2 名女性）。脱落：头痛（2 例），膝盖问题（无法参加，1 例），个人原因（1 例）。平均年龄（范围）为 45.4 岁（27.2-65.1），19 名参与者中 13 名为白人，10 名为男男性接触者。在 w12-w36 期间未观察到 CSF 标志物的变化。总体 NC 功能没有改善：总年龄调整后的 z 分数提高了 0.27（加权配对 t 检验；p=0.11）；仅执行功能，年龄调整后的 z 分数提高了 0.54（p=0.03）。MRI 脑参数无变化。DRV 血浆：CSF 浓度比在 w12（132）和 w36（112）之间没有变化（p=0.577，Wilcoxon 符号秩检验）。MVC 血浆：CSF 浓度比为 35 在 w36。未观察到神经炎症标志物的变化。在这项小型研究中，在稳定的 DRV/r 单药治疗中添加 24w 的 MVC 150mgqd 可能改善了执行功能，而对整体 NC 没有影响。不能排除学习效应。这种效果应该进一步评估。
