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ABSTRACT & COMMENTARY
By Dean L. Winslow, MD, FACP, FIDSA
Clinical Professor of Medicine and Pediatrics Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Associate Editor of Infectious Disease Alert
Dr. Winslow is a consultant for Siemens Diagnostic
SYNOPSIS: 147 patients on stable antiretroviral therapy (ART) were randomized to receiving rosuvustatin 10 mg daily or placebo. After 24 weeks rosovustatin both reduced cystatin C and slowed kidney function decline as assessed by a serum creatinine-based equation.
SOURCE: Longenecker CT, et al. Rosovustatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial. CID 2014;59:1148-56.
The Stopping Atherosclerosis and Treating Unhealthy Bone with Rosovustatin in HIV (SATURN-HIV) trial randomized 147 patients on stable ART with LDL cholesterol <=130 mg/dL to blinded rosovustatin 10 mg daily or placebo. Baseline and 0- to 24-week changes in plasma cystatin C, measures of vascular disease, inflammation and immune activation were measured.
The median age of patients was 46 with 78% male and 68% African-American. Tenofovir (TDF) was used in 88% and protease inhibitors (PI’s) in 49% of subjects. Baseline cystatin C was associated with carotid intima-media thickening by ultrasound and epicardial adipose tissue independently of age, sex, and race. Using the CKD-EPI creatinine-based equation to estimate glomerular filtration rate (eGFR), after 24 weeks statin use slowed mean eGFR decline (+1.68 mL/min in the statin group vs. -3.08 mL/min in the placebo group) and decreased mean cystatin C (-0.034 mg/L vs. +0.010 mg/L). Within the statin group changes in cystatin C correlated with changes in endothelial function (flow-mediated dilation and hyperemic velocity-time integral), endothelial activation (sVCAM and sICAM), inflammation (IL-6, sTNF-RI and sTNF-RII) and T-cell activation (T-cell CD38 and HLA-DR expression).
One of the unfortunate problems of HIV disease pathogenesis is that despite effective control of HIV replication by HAART, elevated levels of systemic immune activation, inflammation and coagulation persist (compared to age-matched HIV-negative controls). This is felt to contribute to diverse conditions including HIV-associated nephropathy, more rapid progression to cirrhosis in HIV patients co-infected with HBV and HCV, and even atherosclerosis.
Another concern is that while TDF-containing ART (and perhaps other antiretroviral agents), while very effective, clearly result in fairly significant (and often irreversible) reductions in eGFR.
Cystatin C is an interesting molecule since it is elevated both in the presence of inflammation and in patients with reduced GFR. The significant effect of rosovustatin on reducing cystatin C, while reducing more direct measures of inflammation, endothelial function and reducing the decline in renal function is good news. If additional studies confirm this to be a class effect of statins, adjunctive use of statins in HV may become standard of care, as it has been for several years in patients with diabetes.