Tenofovir Adherence to Rapidly Guide and Evaluate PrEP and HIV Therapy

NCT03012607 | Completed

• 2 other identifiers: STUDY00000058R21AI127200-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are critical to the success of HIV treatment and therapeutic prevention. No accurate, objective point-of-care test is available to monitor adherence to either ART or PrEP. The inability to accurately identify poorly adherent patients will lead to more HIV infections (from failed PrEP and non-suppressive ART), more drug-resistant virus (selected by failing ART), and unnecessary switching to costly second- or third-line ART (when first-line regimens with virologic efficacy but non-adherence are stopped inappropriately). To address this critical knowledge gap, the investigators have developed a novel point-of-care test to detect the presence of tenofovir-the most common drug in both ART and PrEP treatments worldwide-in fingerprick blood or urine as an objective measure of ART and PrEP adherence. Our central hypothesis is that the pharmacokinetics of tenofovir in blood and urine will support point-of-care tenofovir detection as an objective measure of adherence, and that our point-of-care tenofovir assay will have the ability to discriminate different drug adherence levels. The investigators will test our central hypotheses by pursuing the following two specific aims: (1) To assess our novel point-of-care tenofovir (TFV) assay in whole blood and urine specimens within a controlled pharmacokinetic study of HIV-negative adults receiving tenofovir disoproxil fumarate (TDF) with low, moderate, and perfect adherence; and (2) To validate our novel point-of-care tenofovir (TFV) assay on blood and urine specimens using an existing biorepository from a real-world clinical HIV prevention study. This work is innovative because it develops an entirely new category of rapid diagnostic testing for monitoring ART and PrEP adherence at the clinical point of care. Our rapid assay will help clinicians identify patients in need of more adherence counseling, which when implemented will prevent HIV acquisition, emergence of drug resistant virus, and unnecessary ART regimen switching-measures that will improve national HIV programs and help preserve the global supply of an effective HIV medication.

Conditions

Hiv

Keywords

PrEP

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration versus time curve (AUC) of Truvada concentration

  Area under the plasma concentration versus time curve (AUC) of Truvada concentration

  24, 48, 72 hours post-dose

Secondary Outcomes (3)

• Maximum plasma concentration of Truvada

  24, 48, 72 hours post-dose

• Renal clearance of Truvada

  24, 48, 72 hours post-dose

• Time to Maximum Plasma Concentration(Cmax) of Truvada

  24, 48, 72 hours post-dose

Study Arms (3)

Perfect Adherence

EXPERIMENTAL

Participants will receive a single tablet of TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET \[TRUVADA\] once daily for 6 weeks

Drug: Truvada

Moderate Adherence

EXPERIMENTAL

Participants will receive a single tablet of TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET \[TRUVADA\] 4 times per week (Monday, Wednesday, Friday, and Saturday) for 6 weeks

Drug: Truvada

Poor Adherence

EXPERIMENTAL

Participants will receive a single tablet of TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET \[TRUVADA\] 2 times per week (Monday, Thursday) for 6 weeks

Drug: Truvada

Interventions

Truvada DRUG

Participants will be randomized into 1 of 3 groups (10 participants/group) to receive a controlled number of doses of tenofovir disoproxil fumarate (TDF, 300mg) in a combination pill with emtricitabine (FTC, 200mg) (Truvada®)

Moderate Adherence; Perfect Adherence; Poor Adherence

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 and \<50 years old
• HIV and Hepatitis B surface Ag negative
• Normal renal function (estimated GFR \>60 mL/min by the Cockcroft-Gault equation)
• Willing/able to provided written informed consent

You may not qualify if:

• Pregnant female
• Any significant lab abnormality of neutrophil count, hemoglobin, platelets, AST, or ALT (Defined as Grade ≥3 by DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, Nov. 2014)
• History of using PrEP or thought to be eligible to receive PrEP.
• Any clinically significant diseases or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, might compromise participation in this study
• Any concurrent participation in another clinical trial

Sponsors & Collaborators

• University of Washington: lead
• Chiang Mai University: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Sanpatong Hospital

Chiang Mai, Thailand

Location

Related Publications (2)

• Drain PK, Kubiak RW, Siriprakaisil O, Klinbuayaem V, Quame-Amaglo J, Sukrakanchana PO, Tanasri S, Punyati P, Sirirungsi W, Cressey R, Bacchetti P, Okochi H, Baeten JM, Gandhi M, Cressey TR. Urine Tenofovir Concentrations Correlate With Plasma and Relate to Tenofovir Disoproxil Fumarate Adherence: A Randomized, Directly Observed Pharmacokinetic Trial (TARGET Study). Clin Infect Dis. 2020 May 6;70(10):2143-2151. doi: 10.1093/cid/ciz645.

  PMID: 31314073 DERIVED

• Cressey TR, Siriprakaisil O, Klinbuayaem V, Quame-Amaglo J, Kubiak RW, Sukrakanchana PO, Than-In-At K, Baeten J, Sirirungsi W, Cressey R, Drain PK. A randomized clinical pharmacokinetic trial of Tenofovir in blood, plasma and urine in adults with perfect, moderate and low PrEP adherence: the TARGET study. BMC Infect Dis. 2017 Jul 14;17(1):496. doi: 10.1186/s12879-017-2593-4.

  PMID: 28705153 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Paul Drain, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

• Tim R Cressey, PhD

  Chiang Mai University

  PRINCIPAL INVESTIGATOR

• Oraphan Siriprakaisil, MD

  Sanpatong Hospital, Chiang Mai

  PRINCIPAL INVESTIGATOR

• Virat Klinbuayaem, MD

  Sanpatong Hospital, Chiang Mai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 6, 2017
• Study Start: January 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: February 7, 2020

Record last verified: 2020-02

Locations

TH (1)