Effect of Pitavastatin on Kidney Function in HIV-infected Persons

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 DESCRIPTION (provided by applicant): Effect of Pitavastatin on Renal Function in HIV-infected Persons on stable ART Despite advances in antiretroviral treatment (ART) and the reduction in AIDS-related opportunistic infections, HIV-infected persons have persistent systemic inflammation that contributes to end organ diseases, including chronic kidney disease (CKD). Both traditional (older age, black race, hypertension, diabetes) and HIV-related (chronic viral infection, immunosuppression, inflammation, excess oxidative stress, ART toxicities) factors have been demonstrated to contribute to CKD in the setting of HIV infection. HMG-coA reductase inhibitors (i.e. statins) not only reduce LDL cholesterol but also exert potent anti-inflammatory effects that may be relevant to prevent the progression of kidney disease in diseases like HIV infection which is characterized by heightened inflammation. In this proposal, we will leverage the infrastructure of the NIH-funded REPRIEVE trial in which 6,500 HIV-infected participants with eGFR >60ml/min/1.73m2 will be randomized to 4mg pitavastatin or placebo to reduce the incidence of atherosclerotic cardiovascular events. In an effort to streamline the study, measures of kidney function are not routinely performed. By adding collection of urine and blood from annual visits in 2,500 participants, we propose to assess whether pitavastatin therapy can prevent a ≥30% eGFR decline, a recommended surrogate endpoint for CKD, and the development of albuminuria (ACR >30mg/g). We will also evaluate the effect of pitavastatin in sub-groups of HIV-infected participants for whom the risk of CKD has been demonstrated to be higher, including persons of older age, black race, hypertension, lower CD4 T cell counts, and on tenofovir-containing regimens. Finally, we will assess whether the protective effect of pitavastatin is mediated through mechanistic pathways involving inflammation and oxidative stress. Ultimately, the findings of this study will provide longitudinal data on the epidemiology of CKD in the setting of HIV infection, provide mechanistic insights into whether statins prevent CKD by modulating inflammation and oxidative stress, and potentially change guidelines for the prevention of CKD in this at risk population.