NCT01180075

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
85

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started May 2010

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2010

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

August 10, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 11, 2010

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

December 2, 2014

Status Verified

December 1, 2014

Enrollment Period

4.3 years

First QC Date

August 10, 2010

Last Update Submit

December 1, 2014

Conditions

Outcome Measures

Primary Outcomes (1)

  • Clearance estimates for each drug, adjusted for age and frailty

    From 0, 2, 4-6, and 10-14 hr post-dose blood samples

Study Arms (4)

TDF/FTC/EFV Intensive Sampling-Group A

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

Drug: tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)Procedure: Phlebotomy

TDF/FTC/ATV/r Intensive Sampling Group A

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

Drug: tenofovir/emtricitabine (TDF/FTC)Drug: Atazanavir (ATV)Drug: RitonavirProcedure: Phlebotomy

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

Drug: tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)Procedure: Phlebotomy

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

Drug: tenofovir/emtricitabine (TDF/FTC)Drug: Atazanavir (ATV)Drug: RitonavirProcedure: Phlebotomy

Interventions

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

Also known as: Atripla
TDF/FTC/EFV Intensive Sampling-Group ATDF/FTC/EFV Sparse Sampling Group B

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

Also known as: Truvada
TDF/FTC/ATV/r Intensive Sampling Group ATDF/FTC/ATV/r Sparse Sampling Group B

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

Also known as: Reyataz
TDF/FTC/ATV/r Intensive Sampling Group ATDF/FTC/ATV/r Sparse Sampling Group B

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

Also known as: Norvir
TDF/FTC/ATV/r Intensive Sampling Group ATDF/FTC/ATV/r Sparse Sampling Group B
PhlebotomyPROCEDURE

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

TDF/FTC/ATV/r Intensive Sampling Group ATDF/FTC/ATV/r Sparse Sampling Group BTDF/FTC/EFV Intensive Sampling-Group ATDF/FTC/EFV Sparse Sampling Group B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

HIV Positive patients on a stable regimen consisting of either efavirenz/tenofovir/emtricitabine or atazanavir boosted with ritonavir/tenofovir/emtricitabine

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

  • 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.

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for determining drug concentrations and for future genetic testing of drug metabolizing enzymes and transporters will be stored for up to 5 years.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

TenofovirEfavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug CombinationEmtricitabineEmtricitabine, Tenofovir Disoproxil Fumarate Drug CombinationAtazanavir SulfateRitonavirPhlebotomy

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsOxazinesHeterocyclic Compounds, 1-RingDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesDrug CombinationsPharmaceutical PreparationsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesPyridinesOligopeptidesPeptidesAmino Acids, Peptides, and ProteinsThiazolesSulfur CompoundsAzolesBlood Specimen CollectionSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesTherapeuticsSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Julie B Dumond, PharmD

    University of North Carolina, Chapel Hill

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

August 10, 2010

First Posted

August 11, 2010

Study Start

May 1, 2010

Primary Completion

August 1, 2014

Study Completion

August 1, 2014

Last Updated

December 2, 2014

Record last verified: 2014-12

Locations