Pharmacogenomic of Atazanavir/Efavirenz (ATV/EFV)

HIV Infections Clinical Trial

Official title:

Impact of Pharmacogenomics on Antiretroviral Drugs (Atazanavir and Efavirenz) Concentration and Treatment Response in HIV-infected Adults Study-team

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01138267
• Other study ID #: HIV-NAT103
• Status: Completed
• Start date: May 2009
• Est. completion date: December 2010

Study information

• Verified date: July 2020
• Source: The HIV Netherlands Australia Thailand Research Collaboration
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
Thailand	HIV-NAT Thai Red Cross AIDS Research Center	Bangkok

Sponsors (5)

Lead Sponsor	Collaborator
The HIV Netherlands Australia Thailand Research Collaboration	Chulalongkorn University, Kirby Institute, Radboud University, South East Asia Research Collaboration with Hawaii

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 years
Secondary	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		2 years

External Links

•   HIV Netherland Australia Thailand Research Collaboration (HIV-NAT)