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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Seropositivity, PCSK9, Dyslipidemias

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV-infected patients<br>HIV-infected adult male or female patients who are HIV treatment naive and initiate antiretroviral therapy including a protease inhibitor during the follow up period. | |
| HIV-uninfected patients<br>HIV-uninfected adult male or female patients. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Dyslipidemia, Dyslipidemia, Protease Inhibitor, Ritonavir, PCSK9, Observational