Pharmacogenomics of New Antiretrovirals

Completed

• Conditions: HIV

• Registration Number: NCT02514369
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

Some genetic polymorphisms are known to interfere with ARV metabolism and are therefore likely to explain some of the inter-individual variations (efficacy,toxicity,resistance) observed during ART. The most common form of human DNA variations consists of a change of a base in the nucleotide sequence of an individual at a given position, the single nucleotide polymorphism (SNP). Therefore,the purpose of this research will be the identification and characterization of the clinical impact of several SNPs in gene coding for transport proteins (e.g.ABCB1,ABCC1) and biotransformation enzymes (e.g.CYP3A4,CYP2B6) known to be involved in the pharmacokinetic pathway of selected ARV drugs for which the therapeutic response is difficult to predict. Aside,the influence of these SNPs on the response to treatment (CD4+cell,viral load) and on the toxicity will be evaluated. Plasma concentrations of ARV drugs correlate with therapeutic efficacy but also with the risk of toxicity and of virological failure, which is the basis of the therapeutic drug monitoring. However,given the intracellular location of HIV, analyzing intracellular drug concentrations is fundamental and the investigators will also focus of this new topic.

Detailed Description

Some genetic polymorphisms are known to interfere with ARV metabolism and are therefore likely to explain some of the inter-individual variations (efficacy,toxicity,resistance) observed during ART. The most common form of human DNA variations consists of a change of a base in the nucleotide sequence of an individual at a given position, the single nucleotide polymorphism (SNP). Therefore,the purpose of this research will be the identification and characterization of the clinical impact of several SNPs in gene coding for transport proteins (e.g.ABCB1,ABCC1) and biotransformation enzymes (e.g.CYP3A4,CYP2B6) known to be involved in the pharmacokinetic pathway of selected ARV drugs for which the therapeutic response is difficult to predict. Considering that CYP3A5 may represent up to 50% of the total hepatic CYP3A content in CYP3A5\*1 allele carriers, the CYP3A5 genetic polymorphism may be therefore the most important genetic contributor not only to interindividual but also to interracial differences in CYP3A-dependent drug clearance.

Aside,the influence of these SNPs on the response to treatment (CD4+cell,viral load) and on the toxicity will be evaluated.

Plasma concentrations of ARV drugs correlate with therapeutic efficacy but also with the risk of toxicity and of virological failure, which is the basis of the therapeutic drug monitoring. However,given the intracellular location of HIV, analyzing intracellular drug concentrations is fundamental and the investigators will also focus of this new topic.

Study Timeline

• Study Start: 2012-11
• Study First Submitted: 2015-07-30
• Study First Submitted QC: 2015-07-31
• Study First Posted: 2015-08-03
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-11
• Last Update Posted: 2024-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 179

Inclusion Criteria

• HIV-1 positive treated with drug of interest

Exclusion Criteria

• <18 years old

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Impact of pharmacogenomics on plasma concentration of new antiretroviral drugs	up to 48 months	The geometric mean (GM) of cell associated concentration and plasmatic concentration of ARV drug
Impact of pharmacogenomics on intracellular concentration of new antiretroviral drugs	up to 48 months	The geometric mean (GM) of cell associated concentration and plasmatic concentration of ARV drug

Trial Locations

Locations (1)

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium