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

Sponsor

Franck Boccara (Other)

Overall Status

Completed

CT.gov ID

NCT03139630

Collaborator

National Agency for Research on AIDS and Viral Hepatitis (ANRS) (Other), Institut National de la Santé Et de la Recherche Médicale, France (Other), Amgen (Industry)

193

Enrollment

Location

Duration (Months)

31.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Seropositivity Dyslipidemias PCSK9

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.

Study Design

Study Type:

Observational

Actual Enrollment :

193 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Sep 1, 2016

Actual Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
HIV-infected patients 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 HIV-uninfected adult male or female patients.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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