Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial
Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial
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DOI：
10.1016/s2352-3018(14)70014-1
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发表时间：
2014-10-01
期刊：
影响因子：
16.1
通讯作者：
Sogaard, Ole S.
中科院分区：
文献类型：
--
作者：
Rasmussen, Thomas A.;Tolstrup, Martin;Sogaard, Ole S.
背景激活潜伏病毒的表达是一种可能成为HIV治愈方法的一部分的方法。我们评估的能力，组蛋白去乙酰化酶抑制剂panobinostat破坏HIV-1的潜伏期和安全性，这一strategy.Methods在1/2期临床试验，我们包括aviraemic成人艾滋病毒治疗在奥胡斯大学医院，丹麦。参与者接受口服帕比司他（20 mg），每周三次，每隔一周，持续8周，同时维持联合抗逆转录病毒治疗。主要结果是细胞相关未剪接HIV RNA相对于基线的变化。次要终点为安全性、血浆HIV RNA、总HIV DNA和整合HIV DNA、每百万CD 4 T细胞感染单位以及抗逆转录病毒治疗可选分析治疗中断期间至病毒反弹的时间。该试验在ClinicalTrial.gov注册，编号NCT 01680094。当患者服用帕比司他时，细胞相关的未剪接HIV RNA水平在所有时间点均显著增加（p
Background Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy.Methods In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094.Findings We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased significantly at all timepoints when patients were taking panobinostat (p