Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide
Condition: Hiv
Intervention: FTC/TAF
Intervention description: Participants in cohorts 1a&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 1a) Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence.
1b) Ten healthy subjects will be given one daily dose of TAF/FTC under direct observation to ensure adherence. Morning (not first morning) urine and plasma samples will be collected starting the day the dose is given (1 hr post-dose) and every day thereafter for 6 days.
2) Ten HIV-positive patients who have had undetectable viral loads for greater than 12 weeks (and a recent undetectable viral load in the previous 4 weeks) on an antiretroviral regimen containing TAF/FTC (i.e. Genvoya™, Odefsey™, or Descovy™ in combination with another HIV medication or medications) will have one-time pre-dose urine (early morning) and plasma samples drawn for tenofovir (TFV) concentration, as well as a comprehensive metabolic panel for measurement of creatinine clearance.
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV prevention; PrEP; Descovy

Summary:

      Pre-exposure prophylaxis (PrEP) with Truvada™ (tenofovir/emtricitabine), in which an
      HIV-uninfected individual at high risk for contracting HIV takes antiretroviral medications
      (one pill daily) to maintain blood and genital drug levels sufficient to prevent HIV-1
      acquisition, has been validated in several large international trials that have included men
      who have sex with men and transgender women, heterosexual men and women, and people who use
      injection drugs, as a potential HIV-1 prevention strategy. HIV prevention interventions such
      as this, if adequately disseminated and implemented broadly, may help to curb new HIV
      infections, reduce HIV-associated morbidity and mortality, and reduce health disparities in
      HIV rates among the most at-risk individuals. Assuring adherence to a daily dose of PrEP is
      critical for effective protection against HIV infection. A urine-based test to measure PrEP
      medication levels in the body represents a non-invasive technique to assess adherence and
      ultimately improve PrEP's protective ability.

      TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as
      effective as Truvada™. This study is testing whether a urine test can detect this medication
      in urine.
    

Eligibility criteria:

        Cohort 1(a & b) Inclusion Criteria:

          -  Age 18 or older at the time of signed informed consent

          -  Not currently taking commercial Truvada for PrEP or any other investigational, oral
             medication for the purpose of HIV PrEP

          -  Willing and able to independently provide written informed consent

          -  Tests HIV negative at time of screening using rapid HIV antibody test or serum
             antibody/antigen 4th generation HIV test

        Cohort 1(a & b) Exclusion Criteria:

          -  Evidence of acute or chronic hepatitis B infection at the time of screening

          -  Other clinically significant acute or chronic medical condition, including severe
             infections requiring treatment such as tuberculosis, as determined by the study
             investigator

          -  Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of
             screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) /
             (72 x serum creatinine)

          -  History of bone fractures not explained by trauma

          -  Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS
             grading system

          -  Known allergy/sensitivity to the study drug or its components

          -  Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

          -  Any other clinical condition or prior therapy that, in the opinion of the Principal
             Investigator, would make the subject unsuitable for the study or unable to comply with
             the dosing requirements

        Cohort 2 Inclusion Criteria:

          -  Age 18 or older at the time of signed informed consent

          -  Willing and able to independently provide written informed consent

          -  Last viral load < 20 copies/mL within the last four weeks of screening

          -  Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6
             months

          -  Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months

        Cohort 2 Exclusion Criteria:

          -  Other clinically significant acute or chronic medical condition, including severe
             infections requiring treatment such as tuberculosis, as determined by the study
             investigator

          -  Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of
             screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) /
             (72 x serum creatinine)

          -  Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS
             grading system

          -  Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

          -  Any other clinical condition or prior therapy that, in the opinion of the Principal
             Investigator, would make the subject unsuitable for the study or unable to comply with
             the dosing requirements