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

Phase 1

Completed

• Conditions: PrEP Adherence Monitoring
• Interventions: Drug: Truvada

• Registration Number: NCT02022657
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-09
• Study First Submitted QC: 2013-12-23
• Study First Posted: 2013-12-30
• Study Start: 2014-04
• Primary Completion: 2016-11
• Study Completion: 2017-01
• Results First Submitted: 2018-05-04
• Results First Submitted QC: 2019-03-22
• Status Verified: 2019-04
• Results First Posted: 2019-04-18
• Last Update Submitted: 2019-04-19
• Last Update Posted: 2019-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Ambulatory 18-50 year old adults. Enrollment will target approximately half women and approximately one third African-Americans and one third Latino.
2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of audio-video streaming technology.

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Exclusion Criteria

1. Inability to give informed consent
2. A minimum scalp hair length of 2 cm in the occipital region.
3. Pregnancy or plan to become pregnant or unwillingness to use birth control
4. Current breastfeeding.
5. 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)
6. 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)
7. Positive Hepatitis B (HBV) surface antigen test at screening
8. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.
9. History of non-traumatic, pathologic bone fractures
10. Glomerular Filtration Rate (GFR, creatinine clearance) < 60 ml/min (MDRD equation).
11. Urine dipstick protein ≥ 2+
12. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
13. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
14. Medical condition that alters red blood cell kinetics including hemoglobinopathies or active hemolysis.
15. Any laboratory value or uncontrolled medical conditions that would interfere with the study conditions such as, heart disease and/or cancer.
16. 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
33%/67%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
100%/33%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
33%/100%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
100%/67%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
67%/33%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
67%/100%	Truvada	Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada

Primary Outcome Measures

Name	Time	Method
Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada	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.	TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing.

Trial Locations

Locations (2)

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

University of California San Francisco/San Francisco Department of Public Health; 🇺🇸 San Francisco, California, United States