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

NCT02022657 | Completed Phase 1 Results DMC

• 2 other identifiers: 13-0427U01AI106499
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

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.

Conditions

PrEP Adherence Monitoring

Keywords

Pre exposure prophylaxis; Dried blood spots

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (6)

33%/67%

ACTIVE COMPARATOR

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

33%/100%

ACTIVE COMPARATOR

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

67%/33%

ACTIVE COMPARATOR

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

67%/100%

ACTIVE COMPARATOR

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

100%/33%

ACTIVE COMPARATOR

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

100%/67%

ACTIVE COMPARATOR

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

Interventions

Truvada DRUG

Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP

Also known as: Tenofovir, Emtricitabine

100%/33%; 100%/67%; 33%/100%; 33%/67%; 67%/100%; 67%/33%

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• San Francisco Department of Public Health: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

University of California San Francisco/San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (5)

• Anderson PL, Liu AY, Castillo-Mancilla JR, Gardner EM, Seifert SM, McHugh C, Wagner T, Campbell K, Morrow M, Ibrahim M, Buchbinder S, Bushman LR, Kiser JJ, MaWhinney S. Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01710-17. doi: 10.1128/AAC.01710-17. Print 2018 Jan.

  PMID: 29038282 BACKGROUND

• Ibrahim ME, Castillo-Mancilla JR, Yager J, Brooks KM, Bushman L, Saba L, Kiser JJ, MaWhinney S, Anderson PL. Individualized Adherence Benchmarks for HIV Pre-Exposure Prophylaxis. AIDS Res Hum Retroviruses. 2021 Jun;37(6):421-428. doi: 10.1089/AID.2020.0108. Epub 2020 Dec 10.

  PMID: 33191774 DERIVED

• Grant RM, Pellegrini M, Defechereux PA, Anderson PL, Yu M, Glidden DV, O'Neal J, Yager J, Bhasin S, Sevelius J, Deutsch MB. Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study. Clin Infect Dis. 2021 Oct 5;73(7):e2117-e2123. doi: 10.1093/cid/ciaa1160.

  PMID: 32766890 DERIVED

• Koss CA, Liu AY, Castillo-Mancilla J, Bacchetti P, McHugh C, Kuncze K, Morrow M, Louie A, Seifert S, Okochi H, MaWhinney S, Gandhi M, Anderson PL. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. AIDS. 2018 Sep 24;32(15):2189-2194. doi: 10.1097/QAD.0000000000001935.

  PMID: 30212404 DERIVED

• Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL. Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.

  PMID: 27572401 DERIVED

MeSH Terms

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; 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

Results Point of Contact

• Title: Dr. Peter Anderson
• Organization: Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora

peter.anderson@ucdenver.edu

3037246821

Study Officials

• Peter L Anderson, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2013
• First Posted: December 30, 2013
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: January 1, 2017
• Last Updated: April 30, 2019
• Results First Posted: April 18, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)