Clinical trial NCT01180075: Tenofovir, Emtricitabine, Efavirenz and Atazanavir Pharmacokinetics in the Aging HIV-Infected Population
Official title: Tenofovir, Emtricitabine, Efavirenz and Atazanavir Pharmacokinetics in the Aging HIV-Infected Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2010-08-11
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV Positive patients on a stable regimen consisting of either efavirenz/tenofovir/emtricitabine or atazanavir boosted with ritonavir/tenofovir/emtricitabine

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clearance estimates for each drug, adjusted for age and frailty
timeFrame: From 0, 2, 4-6, and 10-14 hr post-dose blood samples
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Julie B Dumond, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.