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
  Purpose

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.


Condition
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Impact of Pharmacogenomics on Antiretroviral Drugs (Atazanavir and Efavirenz) Concentration and Treatment Response in HIV-infected Adults Study-team

Resource links provided by NLM:


Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA

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.

Estimated Enrollment: 450
Study Start Date: May 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01138267

Locations
Thailand
HIV-NAT Thai Red Cross AIDS Research Center
Bangkok, Thailand, 10330
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Chulalongkorn University
Kirby Institute
Radboud University
South East Asia Research Collaboration with Hawaii
Investigators
Principal Investigator: Kiat Ruxrungtham, MD Chulalongkorn University
  More Information

Additional Information:
No publications provided

Responsible Party: Prof Kiat Ruxrungtham, Chulalongkorn University
ClinicalTrials.gov Identifier: NCT01138267     History of Changes
Other Study ID Numbers: HIV-NAT103
Study First Received: June 4, 2010
Last Updated: February 3, 2011
Health Authority: Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
pharmacogenomics
ATV
EFV
pharmacogenomics of ATV and EFV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Efavirenz
Atazanavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 25, 2014