SWITCHING PROTEASE INHIBITOR COMBO ANTIRETROVIRAL THERAPY TO NEVIRAPINE FOR HIV

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管有无可争辩的好处，但抗逆转录病毒治疗的使用与多种代谢并发症有关。改用更简单的方案可能会保持对病毒的抑制，改善代谢副作用，并提供对这些并发症的发病机制的洞察。我们的目标是仔细研究从成功的基于蛋白酶抑制剂(PI)的抗逆转录病毒方案转换为基于非核苷逆转录酶抑制剂(NNRTI)的奈韦拉平(NVP)方案对病毒学和代谢的影响。40名患者接受了他们第一次成功的基于PI的PI方案(低于40个HIV RNA拷贝/毫升)，将PI转换为NVP。如果患者对NVP不耐受，则允许使用Eefavirenz替代。研究持续时间为48周。每隔12周，受试者有多种病毒学和代谢参数，包括葡萄糖、胰岛素、C-肽、胰高血糖素、胰岛素原、血脂和脂蛋白。18名患者还接受了DEXA扫描、腹部和大腿的核磁共振成像以及胰岛素耐量测试的身体成分评估。95%的患者保持了病毒抑制(95%可信区间88-100%)；只有一名患者失败，另一名患者发展为肝炎。在血糖(降低空腹血糖、胰岛素和改善胰岛素耐量)和脂肪代谢(降低甘油三酯和升高高密度脂蛋白)方面有改善，但在身体成分和骨密度方面没有变化。我们的研究支持PI在高甘油三酯血症和胰岛素抵抗的发生中的致病作用，但在脂肪重新分布综合征中的作用更为有限。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In spite of indisputable benefits, the use of antiretroviral therapy is associated with multiple metabolic complications. Switching to simpler regimens might maintain viral suppression, improve metabolic side effects, and provide insight into the pathogenesis of these complications. Our objective was to carefully characterize the virological and metabolic effects of switching from a successful protease inhibitor (PI)-based antiretroviral regimen to a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with nevirapine (NVP). Forty patients, taking their first successful (less than 40 HIV RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not tolerate NVP, substitution with efavirenz was allowed. The duration of the study was 48 weeks. At 12 weeks intervals subjects had multiple virological and metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin, blood lipids, and lipoproteins. A subgroup of 18 patients also had body composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as well as insulin tolerance tests. Ninety-five percent of the patients maintained viral suppression (95% CI 88-100%); only one patient failed and another developed hepatitis. There were improvements in glucose (decreased fasting glucose, insulin, and improved insulin tolerance) and lipid metabolism (decreased triglycerides and increased HDL), but no changes in body composition and bone mineral density. Our study supports a pathogenic role for PIs in the development of hypertriglyceridemia and insulin resistance, but a more limited role in the fat redistribution syndrome.