EFV Pharmacokinetics & Pharmacogenomics in Older HIV-infected Patients

NCT01886404 | Completed FDA Drug

• 1 other identifier: 0209-13-FB
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to investigate the steady-state pharmacokinetics of efavirenz in older HIV-infected patients as compared to historical controls; to investigate the relationship of drug exposure to neuropsychiatric side effects and neuropsychological performance; and to explore the role of host polymorphisms in drug metabolism in the older patient.

Conditions

HIV Infection

Keywords

HIV; efavirenz; Sustiva; pharmacokinetics; Pharmacogenomics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of EFV in older HIV-infected patients

  plasma concentrations of efavirenz in older HIV-infected patients measured by Liquid Chromatography Mass Spectrometry (LC-MS-MS).

  one year

Secondary Outcomes (1)

• EFV relation to neuropsychiatric side effects and neuropsychological performance

  one year

Other Outcomes (1)

• Role of Host polymorphisms in Efavirenz metabolism

  one year

Study Arms (1)

Efavirenz Group

Participants will be taking efavirenz as part of their antiretroviral regimen.

Drug: Efavirenz

Interventions

Efavirenz DRUG

HIV-infected subjects currently receiving efavirenz (EFV) containing antiretroviral therapy (ART) will be asked to provide plasma samples. In addition to blood samples for determination of EFV concentrations, we will collect whole blood samples for functional Single Nucleotide Polymorphism (SNP) discovery within known candidate genes of interest in drug metabolism and transport. Subjects will be at steady state for efavirenz when blood samples are collected. EFV is usually taken during the evening hours. The study consists of 2 blood draws at 12 and 18 hours post EFV dose. At the first blood draw, venous blood will be obtained by venous puncture for plasma concentrations of EFV and pharmacogenetics. At 18 hours post EFV dose , a second blood draw by venous puncture will be obtained for EFV plasma concentrations. Demographics and clinical parameters will be collected at the time of the first visit, Neuropsychological tests and questionnaires completed as well.

Also known as: EFV, Sustiva

Efavirenz Group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV Infected Older than 50 years Of Age and Taking Efavirenz as Part of The Antiretroviral regimen

You may qualify if:

• HIV infection.
• years of age or older.
• Ability to provide written informed consent.
• Ability to complete the questionnaires in English, as the questionnaires have not been validated in other languages.
• On stable efavirenz containing antiretroviral therapy for the past 12 weeks and not anticipated to require a change in therapy during the following 6 weeks.

You may not qualify if:

• Completion of treatment for any intercurrent acute infection less than four weeks before study entry. Maintenance or prophylactic therapy is permitted for opportunistic infections.
• Any active, severe psychiatric illness that, in the opinion of the investigator, could confound performance of the study procedures and/or analysis of the test results.
• Active drug or alcohol abuse that, in the investigator's opinion, could compromise compliance with study procedures or confound the analysis of the test results.
• Major neurologic disease such as multiple sclerosis or stroke, active brain infection (except for HIV-1), brain neoplasm, or space-occupying brain lesion.
• Current delirium or intoxication.
• Pregnancy.
• Breastfeeding.
• Any other condition that, in the opinion of the investigator, is a contraindication to participation.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (11)

• Avery LB, VanAusdall JL, Hendrix CW, Bumpus NN. Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid. Drug Metab Dispos. 2013 Feb;41(2):422-9. doi: 10.1124/dmd.112.049601. Epub 2012 Nov 19.

  PMID: 23166317 BACKGROUND

• Clifford DB, Evans S, Yang Y, Acosta EP, Ribaudo H, Gulick RM; A5097s Study Team. Long-term impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals (ACTG 5097s). HIV Clin Trials. 2009 Nov-Dec;10(6):343-55. doi: 10.1310/hct1006-343.

  PMID: 20133265 BACKGROUND

• Crawford KW, Spritzler J, Kalayjian RC, Parsons T, Landay A, Pollard R, Stocker V, Lederman MM, Flexner C; AIDS Clinical Trials Protocol 5015 Team. Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. AIDS Res Hum Retroviruses. 2010 Jun;26(6):635-43. doi: 10.1089/aid.2009.0154.

  PMID: 20560793 BACKGROUND

• Wyen C, Hendra H, Siccardi M, Platten M, Jaeger H, Harrer T, Esser S, Bogner JR, Brockmeyer NH, Bieniek B, Rockstroh J, Hoffmann C, Stoehr A, Michalik C, Dlugay V, Jetter A, Knechten H, Klinker H, Skaletz-Rorowski A, Fatkenheuer G, Egan D, Back DJ, Owen A; German Competence Network for HIV/AIDS Coordinators. Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens. J Antimicrob Chemother. 2011 Sep;66(9):2092-8. doi: 10.1093/jac/dkr272. Epub 2011 Jun 29.

  PMID: 21715435 BACKGROUND

• Tozzi V. Pharmacogenetics of antiretrovirals. Antiviral Res. 2010 Jan;85(1):190-200. doi: 10.1016/j.antiviral.2009.09.001. Epub 2009 Sep 8.

  PMID: 19744523 BACKGROUND

• Ribaudo HJ, Haas DW, Tierney C, Kim RB, Wilkinson GR, Gulick RM, Clifford DB, Marzolini C, Fletcher CV, Tashima KT, Kuritzkes DR, Acosta EP; Adult AIDS Clinical Trials Group Study. Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis. 2006 Feb 1;42(3):401-7. doi: 10.1086/499364. Epub 2005 Dec 27.

  PMID: 16392089 BACKGROUND

• Mutlib AE, Chen H, Nemeth GA, Markwalder JA, Seitz SP, Gan LS, Christ DD. Identification and characterization of efavirenz metabolites by liquid chromatography/mass spectrometry and high field NMR: species differences in the metabolism of efavirenz. Drug Metab Dispos. 1999 Nov;27(11):1319-33.

  PMID: 10534318 BACKGROUND

• Markwalder JA, Christ DD, Mutlib A, Cordova BC, Klabe RM, Seitz SP. Synthesis and biological activities of potential metabolites of the non-nucleoside reverse transcriptase inhibitor efavirenz. Bioorg Med Chem Lett. 2001 Mar 12;11(5):619-22. doi: 10.1016/s0960-894x(01)00012-9.

  PMID: 11266155 BACKGROUND

• Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007 Jun;21(3):217-30. doi: 10.1111/j.1472-8206.2007.00473.x.

  PMID: 17521291 BACKGROUND

• Haas DW, Ribaudo HJ, Kim RB, Tierney C, Wilkinson GR, Gulick RM, Clifford DB, Hulgan T, Marzolini C, Acosta EP. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 2004 Dec 3;18(18):2391-400.

  PMID: 15622315 BACKGROUND

• Fletcher CV, Anderson PL, Kakuda TN, Schacker TW, Henry K, Gross CR, Brundage RC. Concentration-controlled compared with conventional antiretroviral therapy for HIV infection. AIDS. 2002 Mar 8;16(4):551-60. doi: 10.1097/00002030-200203080-00006.

  PMID: 11872998 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

efavirenz

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

• Uriel S Sandkovsky, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2013
• First Posted: June 25, 2013
• Study Start: December 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 12, 2023

Record last verified: 2023-12

Locations

US (1)