Clinical trial NCT02962739: The Cellular Pharmacology of F-TAF in Dried Blood Spots
Official title: The Cellular Pharmacology of F-TAF in Dried Blood Spots
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: healthy volunteers
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2016-11-11
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Adherence to daily dosing is very important for how well Emtricitabine/Tenofovir Alafenamide (F/TAF) works for treatment of chronic human immunodeficiency virus (HIV), or prevention of HIV acquisition. Methods to measure medication adherence to Tenofovir disoproxil fumarate (tenofovir DF, TDF), a similar but different prodrug of tenofovir, have been developed but cannot be extrapolated to F-TAF. By measuring F-TAF (the drug) and metabolites in the blood cells and dried blood spots, the study plans to see if these results predict adherence to taking the drug. The goal of this study is to vary the amount of F-TAF dosing and see if the drug levels in dried blood spots (DBS) change in a predictable way. This study will mimic different levels of adherence (33%, 67%, and 100% of daily dosing) using directly observed therapy (DOT) to establish the relationship between F-TAF in dried blood spots and adherence. Investigators will also measure drug in hair clippings to see if hair or DBS are a better predictor of adherence.


Eligibility criteria: Inclusion Criteria:

1. Ambulatory 18-59 year old adults. Enrollment will proceed without the need to meet specific race/gender targets, but balanced gender and African-Americans and Latino representation will be sought.
2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

Exclusion Criteria:

1. Inability to give informed consent
2. Pregnancy or plan to become pregnant in the next 12 months or unwillingness to use birth control
3. Current breastfeeding
4. High risk of HIV-1 infection, for example:

   * sexually active with an HIV infected partner;
   * men who have sex with men who may engage in condomless intercourse with HIVinfected partners, or
   * partner of unknown status during the study;
   * males or females who exchange sex for money, shelter, or gifts;
   * active injection drug use or during the last 12 months;
   * newly diagnosed sexually transmitted infections in last 6 months
5. Positive screening HIV+ ELISA or suspected acute HIV infection in the opinion of the clinician. Example signs and symptoms of acute HIV infection include combinations of:

   * fever,
   * headache,
   * fatigue,
   * arthralgia,
   * vomiting,
   * myalgia, .
   * diarrhea,
   * pharyngitis,
   * rash,
   * night sweats, and
   * adenopathy (cervical or inguinal)
6. Positive Hepatitis B Virus (HBV) surface antigen test at screening
7. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.
8. Glomerular Filtration Rate (GFR) estimate \< 60 ml/min (MDRD equation).
9. Urine dipstick protein ≥ 2+
10. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
11. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
12. Symptomatic hemoglobinopathies or active hemolysis.
13. History of pathological, non-traumatic bone fractures
14. Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.
15. Prohibited concomitant medications are:

    * investigational agents (within 30 days of enrollment),
    * aminoglycosides,
    * ganciclovir/valganciclovir,
    * chronic high-dose acyclovir/valacyclovir (\>800mg acyclovir or \> 500mg valacyclovir for 7 days),
    * cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively.

Primary outcomes:
measure: Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy
timeFrame: Assessed weekly for 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado- Anschutz Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Peter Anderson, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yager J, Castillo-Mancilla J, Ibrahim ME, Brooks KM, McHugh C, Morrow M, McCallister S, Bushman LR, MaWhinney S, Kiser JJ, Anderson PL. Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots Following Tenofovir Alafenamide: The TAF-DBS Study. J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):323-330. doi: 10.1097/QAI.0000000000002354.