Evaluation of the impact of initiation of protease inhibitor/ritonavir on PCSK9 levels in HIV-infected antiretroviral-naïve patients from the ANRS C09 COPANA cohort.
Background: HIV-infected subjects are at high risk of coronary heart disease (CHD) partly in relation with atherogenic dyslipidemia including increased triglycerides (TG) and LDL-cholesterol (LDL-C). Mechanisms of HIV-associated dyslipidemia are complex, involving HIV itself and some antiretrovirals (ARV), particularly protease inhibitors (PI/r). Elevated proprotein convertase subtilisin kexin 9 (PCSK9) level is associated with increased LDL-C in the general population. How PCSK9 level is regulated in HIV-infected treated patients has never been investigated. Objectives: We aimed to identify factors associated with circulating PCSK9 concentration in ART-naïve and treated patients and to evaluate the impact of 1st line ARV therapy (ART) comprising a PI/r, on PCSK9 level in HIV-infected patients. Methods: Fasting plasma concentrations of PCSK9 were measured using ELISA assay in HIV-infected individuals from the ANRS COPANA cohort, at ART initiation and after one year of PI/r-based therapy without any disruption. Subjects not virologically suppressed at follow-up, or taking any lipid lowering therapies at baseline or during follow-up were excluded. Spearman's correlation coefficient was used to determine the association between PCSK9 levels and metabolic parameters at baseline and under PI/r.
Study Type
OBSERVATIONAL
Enrollment
193
Cardiology Department, Saint Antoine University Hospital
Paris, France
PCSK9 plasma level change after initiation of ART including protease inhibitor boosted with ritonavir (PI/r)
Mean percent change in PCSK9 plasma levels after initiation of ART including protease inhibitor boosted with ritonavir (PI/r)r in naïve HIV-infected patients: comparison of values at ART initiation.
Time frame: 1 year
PCSK9 correlation with lipid parameters
Correlations between PCSK9 levels under PI/r and lipid parameters (LDLc, HDLc, triglycerides) and other parameters (glycemia, HOMA\_IR) - from baseline to end.
Time frame: 1 year
PCSK9 correlation with inflammatory makers/adipocytokines
Comparison of inflammatory makers/adipocytokines (IL6, hsCRP, leptin, adiponectin) and PCSK9 change - from baseline (naive) to after ART initiation.
Time frame: 1 year
PCSK9 comparison between HIV-infected and uninfected patients
Comparisons of PCSK9 levels between controls (HIV-uninfected from blood donors) and HIV-infected patients - from baseline (naive) and after ART initiation.
Time frame: 1 year
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