Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)

这项提案的总体目标是确定HMG-CoA还原酶抑制剂， 匹伐他汀可以减轻老年HIV感染患者因年龄增长而导致的身体功能下降 并找出身体机能受损的关键途径。我们的 以前的研究表明，在以下情况下，身体机能的损害比预期的要大 老年艾滋病毒感染者，跌倒、住院和死亡的风险增加。这个 HIV感染者身体功能受损的潜在机制尚未 尚未阐明，但我们的数据强烈表明与慢性炎症有关。为了测试 无论这种联系是否是偶然的，我们将确定匹伐他汀，一种HMG-CoA还原酶 具有抗炎作用的抑制剂，将改善老年HIV感染者的身体功能 接受有效抗逆转录病毒治疗的成年人，有虚弱及其并发症的风险。之前关于以下方面的数据 他汀类药物对未感染艾滋病毒人群的身体功能的影响是混合的， 一些研究表明是有益的，而另一些研究表明是有害的或无效的。在这个背景下 ，我们建议进行一项随机、双盲、安慰剂对照试验。 在没有他汀类药物适应症的HIV感染成人中评估匹伐他汀是否可以 防止身体机能在四年内下降。我们还将确定是否 匹伐他汀影响被认为是身体功能损伤基础的关键途径，包括 全身炎症增加，肌肉脂肪渗透增加。我们建议的研究 将利用艾滋病临床试验小组和缓刑试验的资源，这是一个大型 由美国国立卫生研究院资助的评估匹伐他汀对心血管疾病影响的随机临床试验 事件。提出以下目标：1)确定匹伐他汀对体力活动的影响 功能，2)评估匹伐他汀影响生理功能的机制途径 功能。我们的研究结果将提供有关潜在益处的关键信息 他汀类药物治疗对身体功能的影响与治疗和负担的潜在危害 老龄化人口中的额外药物。这项研究还将提供对 炎症、肌肉脂肪和身体功能之间的纵向关系。重要的是 这项研究将测试一种新的干预措施，以减少老龄化艾滋病毒患者的功能障碍。 感染者。

The overall goals of this proposal are to determine whether the HMG-coA reductase inhibitor, pitavastatin, can attenuate the aging-related decline in physical function in older HIV-infected persons, and to identify the critical pathways underlying physical function impairment. Our previous work has demonstrated greater than expected impairments in physical function among older HIV-infected persons, with an increased risk of falls, hospitalizations, and mortality. The underlying mechanisms of impaired physical function among HIV-infected persons have not been elucidated, but our data strongly suggest an association with chronic inflammation. To test whether this link is casual, we will determine whether pitavastatin, an HMG-CoA reductase inhibitor with anti-inflammatory effects, will improve physical function, among older HIV-infected adults on effective ART who are at risk for frailty and its complications. Previous data regarding the effects of statins on physical function among populations without HIV have been mixed, with some studies showing a benefit and others showing harm or a null effect. In the setting of this state of true equipoise, we propose a randomized, double-blind, placebo-controlled trial of pitavastatin in HIV-infected adults without a statin indication to evaluate whether pitavastatin can prevent the decline of physical function over four years. We will also determine whether pitavastatin impacts key pathways thought to underlie physical function impairments, including elevated systemic inflammation and increased fatty infiltration of muscle. Our proposed study will leverage the resources of the AIDS Clinical Trials Group and the REPRIEVE trial, a large NIH-funded, randomized clinical trial evaluating the effects of pitavastatin on cardiovascular events. The following aims are proposed: 1) To determine the effects of pitavastatin on physical function, 2) To evaluate mechanistic pathways through which pitavastatin affects physical function. The results of our study will provide critical information regarding the potential benefit of statin therapy on physical function versus the potential harm of treatment and burden of an additional medication in an aging population. The study will also provide key insights into the longitudinal relationships between inflammation, muscle fat, and physical function. Importantly, the study will test a novel intervention to reduce functional impairments among aging HIV- infected persons.