The Cellular Pharmacology of F-TAF in Dried Blood Spots
Condition: Healthy Volunteers
Intervention: emtricitabine 200 mg/tenofovir alafenamide 25mg
Intervention description: 1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg
Intervention MeSH terms: Tenofovir; Emtricitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy volunteers

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.