Pharmacogenomic of Atazanavir/Efavirenz (ATV/EFV)

NCT01138267 | Completed DMC

• 1 other identifier: HIV-NAT103
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

pharmacogenomics; ATV; EFV; pharmacogenomics of ATV and EFV

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The HIV Netherlands Australia Thailand Research Collaboration: lead
• Chulalongkorn University: collaborator
• Kirby Institute: collaborator
• Radboud University Medical Center: collaborator
• SEARCH Research Foundation: collaborator

Study Sites (1)

HIV-NAT Thai Red Cross AIDS Research Center

Bangkok, 10330, Thailand

Location

Related Publications (1)

• Chaivichacharn P, Avihingsanon A, Manosuthi W, Ubolyam S, Tongkobpetch S, Shotelersuk V, Punyawudho B. Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic-Pharmacogenetic Model of HIV-infected Patients in Thailand. Clin Ther. 2020 Jul;42(7):1234-1245. doi: 10.1016/j.clinthera.2020.04.013. Epub 2020 May 22.

  PMID: 32451120 DERIVED

Related Links

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

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.

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Kiat Ruxrungtham, MD

  Chulalongkorn University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 7, 2010
• Study Start: May 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

TH (1)