Pharmacogenomic of Atazanavir/Efavirenz (ATV/EFV)

This study has been completed.
Sponsor:
Collaborators:
Chulalongkorn University
Kirby Institute
Radboud University
South East Asia Research Collaboration with Hawaii
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT01138267
First received: June 4, 2010
Last updated: February 3, 2011
Last verified: February 2011

June 4, 2010
February 3, 2011
May 2009
December 2010   (final data collection date for primary outcome measure)
Frequency of MDR1-3435 allele variants,MDR1-2677 allele variants,UGT1A1 allele variants, frequency of CYP 2B6 variants in efavirenz treatment and compare candidate gene and treatment response of ATV/r or EFV [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01138267 on ClinicalTrials.gov Archive Site
Compare drug conc. of UGT1A1 variant with bilirubin, drug conc. & treatment resp. of ATV/r or EFV, drug conc.for WT, drug conc.for 2B6 variant with EFV toxicity & drug discontinuation, drug conc.or 2B6 variant with long term efficacy & EFV resistance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacogenomic of Atazanavir/Efavirenz (ATV/EFV)
Impact of Pharmacogenomics on Antiretroviral Drugs (Atazanavir and Efavirenz) Concentration and Treatment Response in HIV-infected Adults Study-team

Objectives:

  • To evaluate the impact of genetic polymorphism on ARV drug levels
  • To evaluate the effect of genetic polymorphism/drug levels on long term immunologic and virologic response
  • To correlate the genetic polymorphism/drug levels on antiretroviral toxicities

The long-term objective of this research plan is to characterize impact of pharmacogenomics to HIV drug concentration, toxicities, and response to antiretroviral therapy among HIV-infected adults. A comprehensive understanding of the impact of pharmacogenomics to HIV infection and HIV medication will lead to the development of appropriate intervention such as dose reduction strategies in patients with particular gene(s) correlated with higher drug levels. The dose reduction strategy will decrease long term drug toxicity and cost saving for Thais and Asian Ethnicities.

The overall goal of this study is to characterize role of pharmacogenomic on ARV drug (atazanavir, and efavirenz) levels, its toxicities, and its long term efficacy among HIV-infected adults in Thailand. The specific aims are (1) to evaluate the impact of genetic polymorphism on ARV drug levels (2) to evaluate the effect of genetic polymorphism/ drug levels on long term immunologic and virologic response (3) to correlate the genetic polymorphism/drug levels on antiretroviral toxicities. The proposed study will be analysed in stored samples of the well-established cohort of long-term follow-up study for HIV-infected patients participated in HIV-NAT study protocols, the HIV-NAT006 study. This cohort provide us unique opportunity to study impact of pharmacogenomics on long term treatment response and long term drug toxicities since this cohort was started in 1996. Furthermore, the important factors include ARV regimen, drug toxicities, PBMC, immunological and virological parameters have been collected every 6 months basis in HIV-NAT006 study.

A comprehensive understanding of the impact of pharmacogenomics to HIV infection and HIV medication will lead to development of appropriate intervention, particularly, dose reduction strategy in patient with particular gene correlated with greater drug levels. The dose reduction strategy will decrease long term drug toxicity and cost saving for Thai and Asian Ethnicity.

Observational
Observational Model: Cohort
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:

Patients are divided into 4 groups based on whether they need to redraw their blood.

  1. have adequate samples stored and do not need additional blood draws.
  2. have EFV or ATV blood concentrations samples stored but do not have samples for genotyping. Need extra 5-ml sample.
  3. have samples stored but the samples cannot be used to test for EFV or ATV blood concentrations because the time of drug intake and blood drawn are unknown. Need to redraw 5-ml sample.
  4. have never had both drug concentration and genotyping done. Need to give 10 ml of blood sample to perform both tests.
Non-Probability Sample

HIV-infected participants previously or currently enrolled in any HIV-NAT trials since 1996

HIV Infections
Not Provided
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
450
December 2010
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

Inclusion criteria for pharmacogenomic of ATV:

  1. On low-dose ATV/r at the time blood samples are collected for ATV drug levels
  2. Age > 18 years of age or older with HIV-1 infection
  3. Provided consent form

Inclusion criteria for pharmacogenomic of EFV:

  • On EFV at the time blood samples are collected for EFV levels
  • Age > 18 years of age or older with HIV-1 infection
  • Patients who were on EFV but later switched to another ARV regimen due to toxicity of EFV and have stored sample at time of taking EFV
  • Provided consent form

Exclusion Criteria:

Exclusion criteria for both ATV and EFV

  1. Inability to understand the nature and extent of the study and the procedures required.
  2. Contramedication such as rifampin, proton pump inhibitor (for ATV), etc
  3. Pregnancy during blood drawn for EFV or ATV drug levels
  4. Known renal insufficiency or cirrhosis during blood drawn for EFV or ATV drug levels
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01138267
HIV-NAT103
Yes
Prof Kiat Ruxrungtham, Chulalongkorn University
The HIV Netherlands Australia Thailand Research Collaboration
  • Chulalongkorn University
  • Kirby Institute
  • Radboud University
  • South East Asia Research Collaboration with Hawaii
Principal Investigator: Kiat Ruxrungtham, MD Chulalongkorn University
The HIV Netherlands Australia Thailand Research Collaboration
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP