Pharmacogenomic of Atazanavir/Efavirenz (ATV/EFV) - Full Text View

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Efavirenz Atazanavir Atazanavir sulfate

U.S. FDA Resources

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.

have adequate samples stored and do not need additional blood draws.
have EFV or ATV blood concentrations samples stored but do not have samples for genotyping. Need extra 5-ml sample.
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.
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 (Adult, Senior)
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:

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

Inability to understand the nature and extent of the study and the procedures required.
Contramedication such as rifampin, proton pump inhibitor (for ATV), etc
Pregnancy during blood drawn for EFV or ATV drug levels
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:

HIV Netherland Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site


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 Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Efavirenz Atazanavir Sulfate Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors	Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers HIV Protease Inhibitors Protease Inhibitors Anti-HIV Agents

ClinicalTrials.gov processed this record on September 28, 2016