Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity.
Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity.
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DOI：
10.1038/srep39738
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发表时间：
2016-12-23
影响因子：
4.6
通讯作者：
Toborek M
中科院分区：
文献类型：
--
作者：
Bertrand L;Dygert L;Toborek M
抗逆转录病毒药物（ARVd）的引入改变了艾滋病毒感染的预后，从一种致命疾病变成了一种慢性疾病。然而，即使病毒载量无法检测到，患者仍然会出现多种病变，包括脑血管并发症和中风。据推测，ARVd 的毒副作用可能是造成这些影响的原因。为了解决这个问题，我们评估了几种非核苷逆转录酶抑制剂（NNRTI；依法韦仑、依曲韦林、利匹韦林和奈韦拉平）对血脑屏障完整性的影响，以及它们对中风严重程度的影响。在研究的药物中，依法韦仑（而非其他 NNRTI）改变了claudin-5的表达，增加了内皮通透性，并破坏了血脑屏障的完整性。重要的是，在小鼠大脑中动脉闭塞模型中，依非韦伦暴露增加了中风的严重程度。总而言之，这些结果表明，选定的 ARVd 可以加剧 HIV 相关的脑血管病理。因此，在选择抗逆转录病毒治疗方案时应慎重考虑。
The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen.
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DOI：
10.1097/qad.0000000000001178
发表时间：
2016-10-23
期刊：
AIDS (London, England)
影响因子：
--
作者：
Ferguson D;Clarke S;Berry N;Almond N
通讯作者：
Almond N
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
7.5
作者：
Dragovic, Gordana;Jevtovic, Djordje
通讯作者：
Jevtovic, Djordje
影响因子：
2.2
作者：
d'Ettorre G;Ceccarelli G;Pavone P;Vittozzi P;De Girolamo G;Schietroma I;Serafino S;Giustini N;Vullo V
通讯作者：
Vullo V
影响因子：
3.3
作者：
Adachi, Tetsuo;Yasuda, Hiroyuki;Ikeda, Tsunehiko
通讯作者：
Ikeda, Tsunehiko