NUtraceutical TReatment for hYpercholesterolemia in HIV-infected patients: The NU-TRY(HIV) randomized cross-over trial

Background and aims: Despite hypercholesterolemia has been recognized to increase cardiovascular risk in human immunodeficiency virus (HIV)-infected patients, cholesterol-lowering therapy is underused in this population, due to fear of drug-drug interactions with antiretroviral therapy (ART). We investigated the effects of a nutraceutical combination (NC) on lipid profile, proprotein convertase subtilisin/kexin type 9 (PCSK9), subclinical inflammation and arterial stiffness in ART-treated HIV-infected patients. Methods: This was a prospective randomized open-label trial with a cross-over design including 30 stable HIV-infected patients on ART with low-density lipoprotein cholesterol (LDL-C) >115 mg/dL, not taking lipid-lowering treatment. After a 3-week lipid stabilization period, the effects associated with 3 months of an oral NC containing red yeast rice and berberine vs. no active treatment (noNC) were assessed for plasma total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), lipoprotein(a), PCSK9, high-sensitivity C-reactive protein (hs-CRP) levels and aortic pulse wave velocity (aPWV). Results: At baseline, significant correlations between PCSK9 levels, age (rho = -0.51, p=0.004), waist circumference (rho = 0.36, p=0.005) and CD4+ cell count (rho = -0.40, p=0.027) were observed. NC treatment effects corrected for noNC were significant for TC (-14%, p<0.001), LDL-C (-19%, p<0.001), PCSK9 (-12%, p=0.02), hs-CRP (-14%, p=0.03) and aPWV (-6%, p=0.005). No significant effects were observed for HDL-C, TG and lipoprotein(a). NC treatment was safe and no significant alterations in muscle, liver and immunovirological parameters were observed. No carry over effect was recorded. Conclusions: The tested NC significantly reduced plasma cholesterol and PCSK9 levels, attenuated subclinical inflammation and improved arterial stiffness in stable HIV-infected patients on ART.