Study of Truvada for HIV Pre Exposure Prophylaxis Using Daily Directly Observed Therapy to Look at Potential Interactions Between Truvada and Hormone Therapy

NCT04050371 | Completed Phase 4 Results FDA Drug

• 1 other identifier: A131155
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Truvada (Emtricitabine or FTC and tenofovir disoproxil fumarate or TDF) has been approved for HIV prevention since 2012. Drug concentrations after receipt of oral Truvada for HIV Pre Exposure Prophylaxis (or PrEP) appeared to be lower in transgender women compared to Men who Have Sex with Men (MSM) in the iPrEx study, the landmark study of PrEP for HIV prevention. Concentrations were especially low among transgender women (TGW) reporting use of feminizing hormones. Reasons for the lower drug concentrations may be behavioral or biomedical, or a combination of both. While there are no systemic drug-drug interactions between TDF and oral contraception, there are known interactions involving these classes of medications with drug transporters that could affect drug concentrations in target tissues. Drug-drug interactions with natural estrogens and anti-androgenic agents used for gender affirming hormone therapy among transgender women have not been studied, neither have interactions between emtricitabine and female hormones. Concerns about the impact of PrEP on gender affirming hormone therapy is the main barrier for uptake of PrEP among transgender women. In addition, very little is known about TDF/FTC pharmacokinetics in transgender men using testosterone hormonal therapy. Drug-drug interactions with masculinizing hormones have never been properly investigated as trans gender men have not been formally involved in PrEP clinical trials or demonstrations projects.This small study will assess pharmacokinetic drug-drug interactions between tenofovir disoproxil fumarate/emtricitabine and cross-sex hormone therapy. The I-BrEATHe study is a substudy of the Triumph study, a culturally-relevant community-led PrEP demonstration project in transgender communities. The I- BrEATHe pharmacokinetic substudy will provide Truvada daily using directly observed therapy in 24 transgender women and 24 transgender men over a one month period, and will measure drug and hormone therapy levels in blood collected from participants.

Conditions

HIV Prevention; Transgender Health

Keywords

Pre Exposure Prophylaxis; HIV prevention; Emtricitabine, Tenofovir Disoproxil Fumarate; transgender health; transgender persons; drug combination; androgens; estrogens; drug combinations; transmen; non binary; Truvada; daily observed therapy

Outcome Measures

Primary Outcomes (1)

• Tenofovir Diphosphate Concentration in Dried Blood Spots (DBS)

  Tenofovir diphosphate concentration in dried blood spots at week 4

  After 4 weeks of daily observed dosing of FTC/TDF

Other Outcomes (2)

• Estradiol Concentration

  Baseline and after 4 weeks of daily FTC/TDF

• Total Testosterone

  Baseline and after 4 weeks of daily FTC/TDF

Study Arms (1)

TRUVADA DOT

EXPERIMENTAL

one tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate as single dose with daily observed therapy performed either via video calling, or at study visit, for a total of 28 to 30 days

Drug: 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Interventions

200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate DRUG

All study participants received daily observed therapy with FTC/TDF.

Also known as: Truvada

TRUVADA DOT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: transmen, transwomen and gender non conforming
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects:
• HIV antibody seronegative (negative HIV rapid test),
• years or older,
• Has a smart phone with access to two-way video call capability,
• Willingness to be contacted for a short call every day for 4 weeks,
• Adequate renal function (creatinine clearance ≥ 60 ml/min estimated by the Cockcroft Creatinine Clearance Formula),
• Provides written informed consent,
• For Transgender women:
• Male assigned sex at birth, and self-reported current gender identity as "woman" or "transgender women", or other trans-feminine spectrum identity,
• Current feminizing Hormone Therapy (HT) use for at least 6 months,
• For Transgender men:
• Female assigned sex at birth, and self-reported current gender identity as "man" or "transgender man", or other trans-masculine spectrum identity,
• Current masculinizing Hormone Therapy (HT) use for at least 6 months with testosterone

You may not qualify if:

• Expects to change or discontinue current HT use during the 4 weeks study period,
• Signs of symptoms of acute viral syndrome,
• Use of FTC or TDF in the past 90 days
• Receiving ongoing therapy with any of the following:
• AntiRetroviral Therapy, including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents
• Renal insufficiency documented as Creatinine Clearance \< 60 ml/min
• For masculine-spectrum identifying persons, positive pregnancy test at screening
• At enrollment, has any other condition or factor that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives.

Sponsors & Collaborators

• University of California, San Francisco: lead
• San Francisco AIDS Foundation: collaborator
• California HIV/AIDS Research Program: collaborator

Study Sites (1)

San Francisco AIDS foundation

San Francisco, California, 94103, United States

Location

Related Publications (14)

• Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205. Epub 2010 Nov 23.

  PMID: 21091279 BACKGROUND

• Deutsch MB, Glidden DV, Sevelius J, Keatley J, McMahan V, Guanira J, Kallas EG, Chariyalertsak S, Grant RM; iPrEx investigators. HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV. 2015 Dec;2(12):e512-9. doi: 10.1016/S2352-3018(15)00206-4. Epub 2015 Nov 6.

  PMID: 26614965 BACKGROUND

• Sevelius J. "There's no pamphlet for the kind of sex I have": HIV-related risk factors and protective behaviors among transgender men who have sex with nontransgender men. J Assoc Nurses AIDS Care. 2009 Sep-Oct;20(5):398-410. doi: 10.1016/j.jana.2009.06.001.

  PMID: 19732698 BACKGROUND

• Reisner SL, White Hughto JM, Pardee D, Sevelius J. Syndemics and gender affirmation: HIV sexual risk in female-to-male trans masculine adults reporting sexual contact with cisgender males. Int J STD AIDS. 2016 Oct;27(11):955-66. doi: 10.1177/0956462415602418. Epub 2015 Sep 18.

  PMID: 26384946 BACKGROUND

• Deutsch MB, Green J, Keatley J, Mayer G, Hastings J, Hall AM; World Professional Association for Transgender Health EMR Working Group. Electronic medical records and the transgender patient: recommendations from the World Professional Association for Transgender Health EMR Working Group. J Am Med Inform Assoc. 2013 Jul-Aug;20(4):700-3. doi: 10.1136/amiajnl-2012-001472. Epub 2013 Apr 30.

  PMID: 23631835 BACKGROUND

• Escudero DJ, Kerr T, Operario D, Socias ME, Sued O, Marshall BD. Inclusion of trans women in pre-exposure prophylaxis trials: a review. AIDS Care. 2015;27(5):637-41. doi: 10.1080/09540121.2014.986051. Epub 2014 Nov 28.

  PMID: 25430940 BACKGROUND

• Sevelius JM, Patouhas E, Keatley JG, Johnson MO. Barriers and facilitators to engagement and retention in care among transgender women living with human immunodeficiency virus. Ann Behav Med. 2014 Feb;47(1):5-16. doi: 10.1007/s12160-013-9565-8.

  PMID: 24317955 BACKGROUND

• Reisner SL, Vetters R, White JM, Cohen EL, LeClerc M, Zaslow S, Wolfrum S, Mimiaga MJ. Laboratory-confirmed HIV and sexually transmitted infection seropositivity and risk behavior among sexually active transgender patients at an adolescent and young adult urban community health center. AIDS Care. 2015;27(8):1031-6. doi: 10.1080/09540121.2015.1020750. Epub 2015 Mar 19.

  PMID: 25790139 BACKGROUND

• Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, McMahan V, Bushman LR, Casapia M, Montoya-Herrera O, Veloso VG, Mayer KH, Chariyalertsak S, Schechter M, Bekker LG, Kallas EG, Grant RM; iPrEx Study Team. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012 Sep 12;4(151):151ra125. doi: 10.1126/scitranslmed.3004006.

  PMID: 22972843 BACKGROUND

• Hendrix CW, Andrade A, Bumpus NN, Kashuba AD, Marzinke MA, Moore A, Anderson PL, Bushman LR, Fuchs EJ, Wiggins I, Radebaugh C, Prince HA, Bakshi RP, Wang R, Richardson P, Shieh E, McKinstry L, Li X, Donnell D, Elharrar V, Mayer KH, Patterson KB. Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066). AIDS Res Hum Retroviruses. 2016 Jan;32(1):32-43. doi: 10.1089/AID.2015.0182. Epub 2015 Oct 15.

  PMID: 26414912 BACKGROUND

• Zheng JH, Rower C, McAllister K, Castillo-Mancilla J, Klein B, Meditz A, Guida LA, Kiser JJ, Bushman LR, Anderson PL. Application of an intracellular assay for determination of tenofovir-diphosphate and emtricitabine-triphosphate from erythrocytes using dried blood spots. J Pharm Biomed Anal. 2016 Apr 15;122:16-20. doi: 10.1016/j.jpba.2016.01.038. Epub 2016 Jan 21.

  PMID: 26829517 BACKGROUND

• Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization; 2015 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK327115/

  PMID: 26598776 BACKGROUND

• Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, Thompson M, Grant R, Pathak S, O'Hara B, Gvetadze R, Chillag K, Grohskopf L, Buchbinder SP. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8):e23688. doi: 10.1371/journal.pone.0023688. Epub 2011 Aug 29.

  PMID: 21897852 BACKGROUND

• 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

Related Links

• description of the parent Triumph study of which the I-BrEATHe pharmacokinetic study is a sub study

MeSH Terms

Interventions

Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

PrEP dosing was directly observed while hormone replacement therapy was self-reported. Observation was 4 weeks which is less than required to achieve steady state PrEP drug concentrations, which were mathematically projected for the final analysis.

Results Point of Contact

• Title: Robert Grant
• Organization: UCSF

robert.grant@ucsf.edu

415-323-6658

Study Officials

• Robert M Grant, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will receive Truvada for study duration and will take pills using daily observed therapy.

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 8, 2019
• Study Start: August 3, 2017
• Primary Completion: May 23, 2018
• Study Completion: May 23, 2018
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)