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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03139630

Acronym

COPANA

Enrollment

193

Registered

2017-05-04

Start date

2016-03-31

Completion date

2016-09-30

Last updated

2024-01-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dyslipidemias, HIV Seropositivity, PCSK9

Keywords

HIV, Dyslipidemia, Dyslipidemia, Protease Inhibitor, Ritonavir, PCSK9, Observational

Brief summary

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

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame	Description
PCSK9 plasma level change after initiation of ART including protease inhibitor boosted with ritonavir (PI/r)	1 year	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.

Secondary

Measure	Time frame	Description
PCSK9 correlation with lipid parameters	1 year	Correlations between PCSK9 levels under PI/r and lipid parameters (LDLc, HDLc, triglycerides) and other parameters (glycemia, HOMA\_IR) - from baseline to end.
PCSK9 correlation with inflammatory makers/adipocytokines	1 year	Comparison of inflammatory makers/adipocytokines (IL6, hsCRP, leptin, adiponectin) and PCSK9 change - from baseline (naive) to after ART initiation.
PCSK9 comparison between HIV-infected and uninfected patients	1 year	Comparisons of PCSK9 levels between controls (HIV-uninfected from blood donors) and HIV-infected patients - from baseline (naive) and after ART initiation.

Countries

France

Outcome results