Pharmacogenomics of New Antiretrovirals

HIV Clinical Trial

Official title:

Pharmacogenetics of New Antiretroviral Drugs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02514369
• Other study ID #: ARVLB01
• Status: Completed
• Start date: November 2012
• Est. completion date: December 2016

Study information

• Verified date: January 2024
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 positive treated with drug of interest

Exclusion Criteria:

• <18 years old

Related Conditions & MeSH terms

• HIV

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain	Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

Belkhir L, De Laveleye M, Vandercam B, Zech F, Delongie KA, Capron A, Yombi J, Vincent A, Elens L, Haufroid V. Quantification of darunavir and etravirine in human peripheral blood mononuclear cells using high performance liquid chromatography tandem mass — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of pharmacogenomics on plasma concentration of new antiretroviral drugs	The geometric mean (GM) of cell associated concentration and plasmatic concentration of ARV drug	up to 48 months
Primary	Impact of pharmacogenomics on intracellular concentration of new antiretroviral drugs	The geometric mean (GM) of cell associated concentration and plasmatic concentration of ARV drug	up to 48 months