HIV-associated neurocognitive disorder (HAND) can be represented by neurological and neuropathological abnormalities with a consequence of motor and cognitive loss. It has become a critical unmet medical need for infected people, and the number continues to rise every year. Pathological investigations have revealed its occurrence due to the release of free radicals from the HIV infected microglia and macrophages. So far, no effective clinical trials have been conducted for its treatment other than the use of some antiretroviral therapies which have failed to show good results due to poor CNS penetration and hence low CNS distribution. This collective information from the updated literature reports motivated us to share the idea of conjugated products of antiretroviral agents and antioxidants leading to better brain penetration abilities due to higher log p values, higher molecular weight and possibly low toxicity and better neuroprotective action. In this Viewpoint, we have attempted to analyze the chemical and pharmacological classes of antiretroviral agents (ARAs) and their clinical failures for the treatment of cognitive dysfunction due to HIV infection. As the causes of clinical insufficiency of antiretroviral agents and neuropathological mechanisms of HAND have been well established, it would be a good opportunity for medicinal chemists to develop new potential antiretroviral agents or to improve their molecular properties for better therapeutic implications. Furthermore, in silico based molecular properties have been investigated correlating them to the brain penetration abilities.

中文翻译：

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抗逆转录病毒药物增强CNS渗透能力的分子特性研究，用于治疗HIV相关的神经认知障碍认知障碍。

与HIV相关的神经认知障碍（HAND）可以表现为神经和神经病理异常，并伴有运动和认知丧失。对于已感染的人来说，它已经成为医疗服务的关键未得到满足，并且这个数字每年都在增长。病理研究表明，其发生是由于感染了艾滋病毒的小胶质细胞和巨噬细胞释放了自由基。迄今为止，除使用某些抗逆转录病毒疗法外，尚未进行任何有效的临床试验，这是由于中枢神经系统渗透性差因而中枢神经系统分布低而未能显示出良好的效果。 p值，更高的分子量以及可能的低毒性和更好的神经保护作用。在这种观点下，我们尝试分析抗逆转录病毒药物（ARAs）的化学和药理分类及其在治疗因HIV感染引起的认知功能障碍方面的临床失败。由于已经充分确定了抗逆转录病毒药物临床不足的原因和HAND的神经病理学机制，对于药物化学家来说，这将是开发新的潜在抗逆转录病毒药物或改善其分子特性以达到更好的治疗意义的好机会。此外，已经研究了基于计算机模拟的分子特性，将其与大脑渗透能力相关联。