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

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.

Timeline

Start

2017-08-03

Primary completion

2018-05-23

Completion

2018-05-23

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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/
• 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.
• 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.

Drugs

Indications

No indication recorded.