Understanding the complications of antiretroviral drugs.
Understanding the complications of antiretroviral drugs.
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了解抗逆转录病毒药物的并发症。
DOI：
10.1086/590155
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Grunfeld,Carl
中科院分区：
文献类型：
--
作者：
Grunfeld,Carl
After the use of combination antiretroviral (ARV) therapy led to improvements in survival among patients with HIV infection and AIDS [1], a wide variety of body composition and metabolic changes appeared that initially were blamed on HIV protease inhibitors (PIs) as a class [2]. However, the global changes attributed to PIs seemed unlikely, for several reasons [3]. First, an understanding of the literature published before the PI era indicates that some changes represented reversal of the effects of HIV infection—essentially, restoration to health. Second, studies always involved HIV-infected patients receiving therapy with 3 drugs, so attribution to a PI was not definitive. Third, the diverse structures of PIs, which were directed against a viral protease with little homology to mammalian proteases, made it unlikely that all PIs would have the same off-target complications at their respective therapeutic levels. Furthermore, facile theories often linked insulin resistance and hypertriglyceridemia. As HIV-infected patients have lived longer, there has been increasing concern over ARV drug toxicities, such as insulin resistance, hypertriglyceridemia with increases in atherogenic non–high-density lipoprotein cholesterol, and coronary artery disease. It therefore became important to define the direct complications of specific ARV drugs. As a consequence, many of us have tested the effects of ARV drugs, especially PIs, on healthy, HIV-seronegative volunteers, to separate the direct toxicities of the specific ARV drug from the effects of controlling HIV infection (reviewed in detail elsewhere [4]). Comparison of the effects seen in HIV-seronegative volunteers with the changes seen in HIV-infected patients receiving combination therapy or undergoing switch therapy in which 1 drug was changed has painted a clearer picture of ARV drug toxicity.We have learned that the increases in low-density lipoprotein cholesterol seen with combination therapy are mostly reversal of the decrease in low-density lipoprotein seen in the host response to HIV [4]. The similar decrease in high-density lipoprotein that is attributable to HIV infection is poorly responsive to PI-based therapy but improves significantly with nonnucleoside reverse-transcriptase inhibitor therapy, although not always back to normal. The increases seen in triglycerides are drug specific, because they are dominantly attributable to ritonavir-containing regimens and are not a general property of PI drugs. Indeed, there is evidence that efavirenz increases triglycerides. Indinavir is the most potent inducer
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茚地那韦会损害健康的艾滋病毒阴性男性的内皮功能。
DOI：
10.1016/j.ahj.2005.06.005
发表时间：
2005
期刊：
American heart journal.
影响因子：
--
作者：
Shankar,SudhaS;Dube,MichaelP;Gorski,JChristopher;Klaunig,JamesE;Steinberg,HelmutO
通讯作者：
Steinberg,HelmutO
影响因子：
158.5
作者：
Friis-Moller, Nina;Reiss, Peter;Lundgren, Jens D.
通讯作者：
Lundgren, Jens D.
HIV感染者的脂肪分布和代谢变化。
DOI：
10.1097/00002030-199912240-00002
发表时间：
1999
期刊：
AIDS (London, England)
影响因子：
--
作者：
Safrin,S;Grunfeld,C
通讯作者：
Grunfeld,C
尽管内皮功能受损，但胰岛素敏感性仍得以保留。
DOI：
10.1152/ajpendo.00006.2006
发表时间：
2006
期刊：
American journal of physiology. Endocrinology and metabolism.
影响因子：
--
作者：
Shankar,SudhaS;Considine,RobertV;Gorski,JChristopher;Steinberg,HelmutO
通讯作者：
Steinberg,HelmutO