COPANA - A09 PCSK 9 Substudy: Impact of Protease Inhibitors on PCSK9 Levels in Naive HIV-Infected Patients

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.

Inclusion criteria

• Naive HIV-infected male or female > 18 years
• Initiation of antiretroviral therapy including a protestase inhibitor during the follow up with blood samples available
• Patients controlled at one year with a VL<400 copies/ml

Exclusion criteria

• Subjects under statin or other lipid lowering drugs (fenofibrate, ezetimibe)