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.
Aging with HIV may be associated with a greater impairment in physical function, contributing to an increased risk of falls, hospitalizations, and death. However, few therapies are effective in slowing physical function decline in people with or without HIV. Using the infrastructure of a large, NIH-funded, randomized clinical trial, we propose to examine whether pitavastatin, an HMG-coA reductase inhibitor with anti-inflammatory properties, can slow or prevent the decline in physical function of adults aging with HIV infection.
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