Clinical trial NCT03139630: COPANA - A09 PCSK 9 Substudy: Impact of Protease Inhibitors on PCSK9 Levels in Naive HIV-Infected Patients
Official title: COPANA - A09 PCSK 9 Substudy: Impact of Protease Inhibitors on PCSK9 Levels in Naive HIV-Infected Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Seropositivity
Dyslipidemias
PCSK9
Keywords: HIV, Dyslipidemia
Dyslipidemia
Protease Inhibitor
Ritonavir
PCSK9
Observational
Lead sponsor: Saint Antoine University Hospital
Sponsor class: OTHER
Collaborators: name: National Agency for Research on AIDS and Viral Hepatitis (ANRS)
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Amgen
First posted: 2017-05-04
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-infected patients: 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: adult adult male or female patients.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: PCSK9 plasma level change after initiation of ART including protease inhibitor boosted with ritonavir (PI/r)
timeFrame: 1 year
Secondary outcomes:
measure: PCSK9 correlation with lipid parameters
timeFrame: 1 year
measure: PCSK9 correlation with inflammatory makers/adipocytokines
timeFrame: 1 year
measure: PCSK9 comparison between HIV-infected and uninfected patients
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Cardiology Department, Saint Antoine University Hospital
Study officials:
affiliation: Saint Antoine University Hospital
name: Franck Boccara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boccara F, Ghislain M, Meyer L, Goujard C, Le May C, Vigouroux C, Bastard JP, Fellahi S, Capeau J, Cohen A, Cariou B; ANRS-COPANA Study Group. Impact of protease inhibitors on circulating PCSK9 levels in HIV-infected antiretroviral-naive patients from an ongoing prospective cohort. AIDS. 2017 Nov 13;31(17):2367-2376. doi: 10.1097/QAD.0000000000001633.