Single Dose Truvada Study

Study Overview
=================
Brief Summary
-----------------
This study examines tenofovir (TFV) drug concentrations in adults one day after taking a single dose of Truvada® - a pill used to prevent and treat HIV infection. The results of this study will be used to improve the (efficacy/accuracy) of a white coat adherence (WCA) detection test - a blood test that can be used to indicate medication adherence. Participants will receive one dose of Truvada®, and provide 2 total samples of blood.

Detailed Description
-----------------
To establish the plasma and peripheral blood mononuclear cells (PBMC) concentrations of TFV and TFV diphosphate (TFV-DP), respectively, following a single oral dose of Truvada® [300 mg tenofovir disoproxil fumarate (TDF) in fixed dose combination with emtricitabine (FTC)], the same formulation used for HIV pre-exposure prophylaxis (PrEP), and in prior benchmarking adherence studies (HPTN 066). This will be compared to steady-state TFV and TFV-DP concentrations to more robustly differentiate single dose concentrations from steady-state concentrations. This is part of a larger project to determine the frequency of white coat adherence in several clinical studies where doses are not observed. For purposes of diagnosing WCA with TDF, the investigators define WCA quantitatively as taking a single dose of TDF preceded by no doses in the prior week. The investigators will compare TFV and TFV-DP concentrations following an observed single oral dose of TDF/FTC to steady-state concentrations of TFV and TFV-DP after daily dosing under observation. The study plan involves a screening visit to assess eligibility, followed by two study visits. Visit one involves pre-dose blood testing, followed by a single dose of Truvada. Visit two occurs 24-hours after visit one, and involves collection of a final post-dose blood sample. Blood will be assessed for tenofovir and tenofovir analyte concentrations.

Official Title
-----------------
Single Observed Dose Administration of Truvada® to Establish Single Dose Pharmacokinetic Standards in Healthy Individuals

Conditions
-----------------
Medication Adherence, HIV Prevention

Intervention / Treatment
-----------------
* Drug: Tenofovir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy with no acute medical illness Willing to provide written informed consent Age 18 years of age or older Negative qualitative urine pregnancy test at screening and on day of dosing, prior to dosing, female participants only HIV-1 negative at screening, as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay At screening, no evidence of hepatic or renal impairment [creatinine clearance > 60 ml/min, total bilirubin ≤ upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 ULN] Exclusion Criteria: Concomitant antiretroviral or other medication use, for which there is a known risk of pharmacokinetic or pharmacodynamic drug interactions. Active medical or psychological condition that, in the opinion of the investigator, might put the volunteer at undue risk or interfere with the participation of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Truvada<br>single oral dose of Truvada® (300 mg tenofovir disoproxil fumarate) | Drug: Tenofovir<br>* pre- and post-dosing measurements of TFV and TFV-DP in plasma and PBMCs.<br>* Other names: Truvada;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Tenofovir (TFV) concentration in ng/mL |  | 24 hours | 
| Peripheral Blood Mononuclear Cells (PBMC) TFV diphosphate (TFV-DP) concentration in femtomole per million cells (fmol/10^6) |  | 24 hours |