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.