Tenofovir, Emtricitabine, Efavirenz and Atazanavir Pharmacokinetics in the Aging HIV-Infected Population

NCT ID: NCT01180075

Last Updated: 2014-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

85 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-05-31

Study Completion Date

2014-08-31

Brief Summary

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Purpose: To see how growing older changes the amount of HIV drugs in the blood of HIV-infected men and women. Many changes happen in the body as it ages that may affect the way drugs are carried in the blood, broken down or removed from the body. This study will look at the amount of drug in the blood and cells of the immune system for patients taking efavirenz, tenofovir and emtricitabine or atazanavir boosted with ritonavir, tenofovir and emtricitabine.

Participants: The population will comprise of 56 (6 for intensive PK and 50 for sparse sampling) HIV-infected adults currently adhering to an antiretroviral regimen containing efavirenz with tenofovir and emtricitabine and the same number and distribution of HIV-infected adults currently adhering to an antiretroviral regimen containing atazanavir boosted with ritonavir with tenofovir and emtricitabine.

Procedures (methods): This study will be completed at the University of North Carolina at Chapel Hill. There will be four groups of subjects: Efavirenz/tenofovir/emtricitabine Group A, Efavirenz/tenofovir/emtricitabine Group B, Atazanavir/ritonavir/tenofovir/emtricitabine Group A, and Atazanavir/ritonavir/tenofovir/emtricitabine Group B.

The initial six subjects (Group A) for intensive PK analysis for each regimen will be recruited from the the UNC ID Clinic or the Moses Cone Health System Infectious Diseases Clinic, and will be comprised of non-frail subjects not currently receiving interacting drugs. If subjects provide informed consent, timed blood samples will be obtained to determine pharmacokinetic parameters around an observed dose of one of the two study regimens. A whole blood sample will also be collected and stored for potential drug metabolizing enzymes and transporters genotyping in the future. Group A subjects will complete a follow-up visit after their sampling visit.

50 subsequent subjects (Group B) for each regimen will be screened simultaneously, with no more than 10 subjects enrolled for each regimen in Group B prior to the completion and analysis of Group A. These subjects will also be recruited from either site. Group B subjects will have one or two sampling visits with 1 to 4 blood samples obtained at each visit, with a stored sample for future genotyping obtained on one of the visits. Samples will be collected just prior to a dose, at 2 hours, between 4 and 6 hrs, and between 10 and 14 hours after a medication dose. These visits may coincide with the subjects' regularly scheduled visit to the clinic, or be scheduled separately, depending on the preference and availability of the subject.

Detailed Description

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Conditions

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Human Immunodeficiency Virus

Study Design

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Study Time Perspective

PROSPECTIVE

Study Groups

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TDF/FTC/EFV Intensive Sampling-Group A

Patients receiving TDF/FTC/EFV who undergo intensive pharmacokinetic sampling over 24 hours

tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)

Intervention Type DRUG

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Phlebotomy

Intervention Type PROCEDURE

Multiple blood draws will be performed in the study, and vary depending on the group.

TDF/FTC/ATV/r Intensive Sampling Group A

Patients receiving TDF/FTC/ATV/r who undergo intensive pharmacokinetic sampling over 24 hours

tenofovir/emtricitabine (TDF/FTC)

Intervention Type DRUG

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Atazanavir (ATV)

Intervention Type DRUG

Patients receiving this drug for clinical care at 300mg with 100mg ritonavir daily will be enrolled.

Ritonavir

Intervention Type DRUG

Patients receiving this drug for clinical care at 100mg daily with 300mg atazanavir will be enrolled.

Phlebotomy

Intervention Type PROCEDURE

Multiple blood draws will be performed in the study, and vary depending on the group.

TDF/FTC/EFV Sparse Sampling Group B

Patients receiving TDF/FTC/EFV who undergo sparse pharmacokinetic sampling on 1 or 2 visits depending on subject's availability

tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)

Intervention Type DRUG

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Phlebotomy

Intervention Type PROCEDURE

Multiple blood draws will be performed in the study, and vary depending on the group.

TDF/FTC/ATV/r Sparse Sampling Group B

Patients receiving TDF/FTC/ATV/r who undergo sparse pharmacokinetic sampling on 1 or 2 visits depending on subject's availability

tenofovir/emtricitabine (TDF/FTC)

Intervention Type DRUG

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Atazanavir (ATV)

Intervention Type DRUG

Patients receiving this drug for clinical care at 300mg with 100mg ritonavir daily will be enrolled.

Ritonavir

Intervention Type DRUG

Patients receiving this drug for clinical care at 100mg daily with 300mg atazanavir will be enrolled.

Phlebotomy

Intervention Type PROCEDURE

Multiple blood draws will be performed in the study, and vary depending on the group.

Interventions

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tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Intervention Type DRUG

tenofovir/emtricitabine (TDF/FTC)

Patients receiving this drug for clinical care at standard dosages will be enrolled.

Intervention Type DRUG

Atazanavir (ATV)

Patients receiving this drug for clinical care at 300mg with 100mg ritonavir daily will be enrolled.

Intervention Type DRUG

Ritonavir

Patients receiving this drug for clinical care at 100mg daily with 300mg atazanavir will be enrolled.

Intervention Type DRUG

Phlebotomy

Multiple blood draws will be performed in the study, and vary depending on the group.

Intervention Type PROCEDURE

Other Intervention Names

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Atripla Truvada Reyataz Norvir

Eligibility Criteria

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Inclusion Criteria

* HIV positive patients
* Able to provide written informed consent
* Able to comply with their treatment regimen and study procedures
* Currently receiving either efavirenz/tenofovir/emtricitabine or atazanavir/ritonavir/tenofovir/emtricitabine as treatment for their HIV infection. Subjects must have been on the regimen for at least 2 weeks
* All women of reproductive potential must have a negative urine pregnancy test
* If participating in sexual activity that could lead to pregnancy, study participant must use at least one reliable method of contraception.

Exclusion Criteria

* Displaying the fraility phenotype (Group A only)
* Receiving an interacting medication
* Having missed \>3 doses of study medication in the past 30 days
* Patients who will not likely remain on the study regimen during the course of study participation.
* Anemia (hemoglobin \<10 g/dL)
* Abnormal screening laboratory findings
* Pregnancy
* Breastfeeding
* Any condition that may interfere with follow-up or the ability to take the study medication appropriately.
* Any clinically significant surgical alterations of the alimentary track, that in the opinion of the investigators, alters the absorption pharmacokinetics of the drugs of interest.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Julie Dumond, PharmD

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Julie B Dumond, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Countries

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United States

References

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Dumond JB, Francis O, Cottrell M, Trezza C, Prince HM, Mollan K, Sykes C, Torrice C, White N, Malone S, Wang R, Van Dam C, Patterson KB, Hudgens MG, Sharpless NE, Forrest A. Tenofovir/emtricitabine metabolites and endogenous nucleotide exposures are associated with p16(INK4a) expression in subjects on combination therapy. Antivir Ther. 2016;21(5):441-5. doi: 10.3851/IMP3017. Epub 2016 Jan 5.

Reference Type DERIVED
PMID: 26731175 (View on PubMed)

Other Identifiers

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1K23AI093156-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-2120

Identifier Type: -

Identifier Source: org_study_id