The Cellular Pharmacology of F-TAF in Dried Blood Spots (TAF-DBS)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado- Anschutz Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 33%/67% dosing; The 33% and 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks; 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks).	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy
Active Comparator: 33%/100% dosing; The 33% dosing regimens will use skipped doses spaced by days (i.e. 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks). 100% will dose daily for 12 weeks, no skipped doses.	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy
Active Comparator: 67%/33% dosing; The 33% and 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks; 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks).	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy
Active Comparator: 67%/100% dosing; 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks. 100% will dose daily for 12 weeks, no skipped doses.	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy
Active Comparator: 100%/33% dosing; The 33% dosing regimens will use skipped doses spaced by days (i.e. 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks). 100% will dose daily for 12 weeks, no skipped doses.	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy
Active Comparator: 100%/67% dosing; 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks. 100% will dose daily for 12 weeks, no skipped doses.	Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg; 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg; Other Names: Descovy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy	Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) respective to dosing regimens of 33%, 67%, 100% of daily dosing.	Assessed weekly for 9 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Peter Anderson, PharmD, University of Colorado, Denver

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: November 8, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: healthy volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: 16-0972

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No