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抗逆转录病毒疗法引起的脂质改变:体外、动物和人体研究

Antiretroviral therapy-induced lipid alterations: in-vitro, animal and human studies.

作者信息

Mallon Patrick W G

机构信息

School of Medicine and Medical Sciences, University College Dublin, Dublin 7, Ireland.

出版信息

Curr Opin HIV AIDS. 2007 Jul;2(4):282-92. doi: 10.1097/COH.0b013e3281e72ca0.

Abstract

PURPOSE OF REVIEW

To describe the clinical features, pathogenesis and therapeutic options for the dyslipidaemia commonly seen in HIV-infected patients on combination antiretroviral therapy.

RECENT FINDINGS

Dyslipidaemia associated with antiretroviral therapy is characterized by elevations in total and low-density lipoprotein-cholesterol and triglycerides, and decreased high-density lipoprotein-cholesterol - a profile with atherogenic potential. Although a multifactorial cause underlies antiretroviral therapy-associated dyslipidaemia, exposure to all three principal classes of antiretroviral medications - protease inhibitors in particular - has been implicated in its development. Protease inhibitors have been shown to affect several molecular pathways important for lipid metabolism, including intranuclear transcription factors and the nuclear proteasome. Although treatment options are limited, with many conventional therapeutic strategies less effective in the presence of ongoing antiretroviral therapy exposure, the increased incidence of cardiovascular disease observed in some HIV-infected cohorts underlies the need for effective management strategies for antiretroviral therapy-associated dyslipidaemia.

SUMMARY

Although use of protease inhibitors is implicated in antiretroviral therapy-associated dyslipidaemia, the extent to which individual protease inhibitors cause dyslipidaemia varies considerably within this drug class. More research is needed to design better tolerated antiretrovirals and improved therapeutic interventions for this common condition.

摘要

综述目的

描述接受联合抗逆转录病毒治疗的HIV感染患者中常见的血脂异常的临床特征、发病机制及治疗选择。

最新发现

与抗逆转录病毒治疗相关的血脂异常的特征是总胆固醇、低密度脂蛋白胆固醇和甘油三酯升高,高密度脂蛋白胆固醇降低——这是一种具有动脉粥样硬化潜力的血脂谱。虽然抗逆转录病毒治疗相关血脂异常有多种病因,但接触所有三类主要抗逆转录病毒药物,尤其是蛋白酶抑制剂,都与其发生有关。蛋白酶抑制剂已被证明会影响脂质代谢的几个重要分子途径,包括核内转录因子和核蛋白酶体。虽然治疗选择有限,许多传统治疗策略在持续接受抗逆转录病毒治疗的情况下效果较差,但在一些HIV感染队列中观察到的心血管疾病发病率增加,凸显了对抗逆转录病毒治疗相关血脂异常采取有效管理策略的必要性。

总结

虽然蛋白酶抑制剂的使用与抗逆转录病毒治疗相关血脂异常有关,但在这一药物类别中,不同蛋白酶抑制剂导致血脂异常的程度差异很大。需要更多研究来设计耐受性更好的抗逆转录病毒药物,并针对这种常见病症改进治疗干预措施。

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