Randomized Trial of Central Nervous System-Targeted Antiretrovirals for HIV-Associated Neurocognitive Disorder
Randomized Trial of Central Nervous System-Targeted Antiretrovirals for HIV-Associated Neurocognitive Disorder
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DOI：
10.1093/cid/cit921
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发表时间：
2014-04-01
影响因子：
11.8
通讯作者：
McCutchan, J. Allen
中科院分区：
文献类型：
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作者：
Ellis, Ronald J.;Letendre, Scott;McCutchan, J. Allen
背景抗逆转录病毒（ARV）药物差异穿透血脑屏障进入中枢神经系统（CNS）组织，可能影响其治疗脑感染的有效性。这项随机对照临床试验（RCT）要求5个研究中心的120名参与者以1：1的比例随机分配至CNS靶向（CNS-T）或非CNS-T ART组。使用自适应随机化方法，在各组之间平衡入组临床因素（如ARV经验）。主要结果是神经认知能力的变化，以从基线到第16周的总体缺陷评分（GDS）的差异来衡量。根据其数据安全性监测委员会的建议，该研究提前终止，原因是招募缓慢且检测到主要结局差异的可能性较低。未发现安全性问题。在筛选的326名参与者中，59名符合入选标准并被随机分配。主要意向治疗分析包括49名完成第16周的参与者。其中包括39名男性和10名女性，平均年龄为44岁（SD，10岁），中位最低值和当前CD 4（+）T细胞计数分别为175个细胞/μ L和242个细胞/μ L。CNS-T组GDS较基线的比例改善（7%; 95%置信区间[CI]，-31%至62%）非显著大于非CNS-T组，代表治疗效应量为0.09（95% CI，-0.48至0.65）。预先规定的次要分析显示趋势相互作用（P = 0.087），表明基线血浆病毒学抑制的参与者可能从CNS-T中获益。这项研究没有发现CNS-T策略对HIV相关神经认知障碍的神经认知益处的证据。不能排除亚组获益或较小的总体获益。
Background. Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into central nervous system (CNS) tissues, potentially influencing their effectiveness in treating brain infection.Methods. This randomized controlled clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-targeted (CNS-T) or non-CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16.Results. The study was terminated early on the recommendation of its data safety monitoring board on the basis of slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 years (SD, 10 years), and median nadir and current CD4(+) T-cell counts of 175 cells/mu L and 242 cells/mu L, respectively. The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval [CI], -31% to 62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect size of 0.09 (95% CI, -.48 to .65). Prespecified secondary analysis showed a trend interaction (P = .087), indicating that participants who had baseline plasma virologic suppression may have benefited from CNS-T.Conclusions. This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. A benefit for a subgroup or small overall benefits could not be excluded.