Pre-Exposure Prophylaxis (PrEP) Adherence Monitoring Using Dried Blood Spots

Study Overview
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Brief Summary
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The primary objective of this study is to define the mean, variance, and dose proportionality for tenofovir-diphosphate(TFV-DP) in dried blood spots resulting from 33%, 67%, and 100% of daily dosing with 200mg emtricitabine and 300mg of tenofovir disoproxil fumarate (as Truvada®). With this information, a model will be established to predict adherence rates to TFV-DP using DBS. Forty-eight healthy HIV-uninfected adult participants who are at low risk for HIV infection will be randomized to one of 6 sequences consisting of two directly observed dosing regimens, 33%/67%, 33%/100%, 67%/33%, 67%/100%, 100%/33%, and 100%/67% with each dose regimen lasting approximately 12 weeks, separated by an approximately 12 week washout period. DBS will be collected at regular intervals, including during the washout. The hypothesis of the study is that levels of TFV-DP in DBS will predict adherence rates in the preceding 1-3 months.

Official Title
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PrEP Adherence Monitoring Using Dried Blood Spots

Conditions
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PrEP Adherence Monitoring

Intervention / Treatment
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* Drug: Truvada


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory 18-50 year old adults. Enrollment will target approximately half women and approximately one third African-Americans and one third Latino. Ability to comply with study procedures, including directly observed dosing visits and availability and use of audio-video streaming technology. Exclusion Criteria: Inability to give informed consent A minimum scalp hair length of 2 cm in the occipital region. Pregnancy or plan to become pregnant or unwillingness to use birth control Current breastfeeding. 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 condom-less intercourse with HIV-infected 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) 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) Positive Hepatitis B (HBV) surface antigen test at screening Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements. History of non-traumatic, pathologic bone fractures Glomerular Filtration Rate (GFR, creatinine clearance) < 60 ml/min (MDRD equation). Urine dipstick protein ≥ 2+ Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL. Medical condition that alters red blood cell kinetics including hemoglobinopathies or active hemolysis. Any laboratory value or uncontrolled medical conditions that would interfere with the study conditions such as, heart disease and/or cancer. Contraindicated concomitant medications (including investigational agents, aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir, cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications (Truvada®) including ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of Emtricitabine (FTC) and tenofovir, respectively).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 33%/67%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|
| Active Comparator: 33%/100%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|
| Active Comparator: 67%/33%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|
| Active Comparator: 67%/100%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|
| Active Comparator: 100%/33%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|
| Active Comparator: 100%/67%<br>Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada | Drug: Truvada<br>* Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP<br>* Other names: Emtricitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada | TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing. | Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre exposure prophylaxis, Dried blood spots