A Pharmacokinetic Evaluation of Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis in Transgender Women

• ClinicalTrials.gov Identifier: NCT03270969
• Recruitment Status: Completed
• First Posted: September 1, 2017
• Last Update Posted: December 19, 2018
• Sponsor: University of Nebraska
• Information provided by (Responsible Party): Kimberly Scarsi, PharmD, MS, BCPS-ID,, University of Nebraska

Study Description

Brief Summary:

Human immunodeficiency virus (HIV) persists worldwide as an immense health burden among vulnerable populations. HIV pre-exposure prophylaxis (PrEP) has offered the promise of limiting the global burden of HIV. The objective of this proposal is to conduct a pharmacokinetic (PK) study in transgender women to describe the pharmacokinetics of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as PrEP within this population.

Condition or disease	Intervention/treatment	Phase
HIV Prevention	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine	Phase 1

Detailed Description:

PrEP is a critical component of comprehensive transgender medical care. The proposed open-label, intensive PK study will inform the pharmacologic impact of combining PrEP and concurrent feminizing hormone regimens. The investigators hypothesize transgender women will achieve similar PrEP concentrations compared to the historical controls, and that hormone concentrations (estrogen and testosterone) will not be affected. The aims of this study are to (1) to determine if concurrent use of TDF/FTC as PrEP in combination with feminizing hormones alters the PK of tenofovir (TFV) and FTC and (2) to determine if concurrent use of PrEP with feminizing hormones alters serum estradiol and testosterone concentrations. To achieve these aims, this study will enroll transgender women who are receiving either oral/sublingual or transdermal estradiol with spironolactone. Using intensive PK sampling, plasma and intracellular TDF/FTC concentrations will be measured after 14 days of oral TDF/FTC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pharmacokinetics of Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-exposure Prophylaxis in Transgender Women Receiving Feminizing Hormone Therapy
• Actual Study Start Date: January 5, 2018
• Actual Primary Completion Date: September 10, 2018
• Actual Study Completion Date: September 10, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: TDF/FTC; Tenofovir Disoproxil Fumarate/Emtricitabine group HIV-uninfected transgender women receiving feminizing hormone therapy plus tenofovir disoproxil fumarate/emtricitabine	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine; Participants will receive daily TDF/FTC for 14 days

Outcome Measures

Primary Outcome Measures :

1. TFV plasma exposure [ Time Frame: 14 days ]
   Intensive PK sampling compared to historical controls

Secondary Outcome Measures :

1. FTC plasma exposure [ Time Frame: 14 days ]
   Intensive PK sampling compared to historical controls
2. Tenofovir-diphosphate (TFV-DP) intracellular concentrations [ Time Frame: 14 days ]
   Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control
3. Emtricitabine-triphosphate (FTC-TP) intracellular concentrations [ Time Frame: 14 days ]
   Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control
4. TFV maximum plasma concentration (Cmax) [ Time Frame: 14 days ]
   Cmax of TFV compared to historical control
5. FTC maximum plasma concentration (Cmax) [ Time Frame: 14 days ]
   Cmax of FTC compared to historical control
6. Estradiol serum concentrations [ Time Frame: 14 days ]
   Before and after intervention
7. Testosterone serum concentrations [ Time Frame: 14 days ]
   Before and after intervention

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: transgender women
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Self identify as a transgender woman.
• Receiving estradiol (oral/sublingual tablets or transdermal patches) with oral spironolactone for at least 3 months prior to study entry.
• Serum estradiol level >100 pg/mL.
• Non-reactive 4th or 5th generation screening test for HIV.
• Adults (19 years or older).
• Able to read and speak English to ensure appropriate ability to obtain informed consent.

Exclusion Criteria:

• Participants will not be included in the study if one, or more, of the following criteria are met:
• Use of drugs known to be contraindicated with TDF, FTC, estradiol, or spironolactone within 30 days of study entry. The study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table and the drug product labeling.
• Use of injectable estradiol (valerate or cypionate).
• Presence of any active condition or clinically significant disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study, including qualifying for non-occupational post-HIV exposure prophylaxis.
• Signs or symptoms of acute HIV infection within the last 30 days.
• Laboratory values obtained within 30 days prior to study entry:
• Creatinine clearance (CrCl) less than 60 mL/min as estimated by the Cockcroft-Gault equation.
• Positive hepatitis B surface antigen and/or hepatitis C antibody.
• Alanine transaminase (ALT), Aspartate transaminase (AST) or alkaline phosphatase > 5x the upper limit of normal (ULN).
• Hemoglobin <10 g/dL.
• Platelets <50,000/mm3.

Contacts and Locations

Locations

United States, Nebraska

University of Nebraska

Omaha, Nebraska, United States, 68198

Sponsors and Collaborators

University of Nebraska

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cirrincione LR, Podany AT, Havens JP, Bares SH, Dyavar SR, Gwon Y, Johnson TM, Amoura NJ, Fletcher CV, Scarsi KK. Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy. J Antimicrob Chemother. 2020 May 1;75(5):1242-1249. doi: 10.1093/jac/dkaa016.

• Responsible Party: Kimberly Scarsi, PharmD, MS, BCPS-ID,, Postdoctoral Research Associate, University of Nebraska
• ClinicalTrials.gov Identifier: NCT03270969
• Other Study ID Numbers: 491-17-FB
• First Posted: September 1, 2017
• Last Update Posted: December 19, 2018
• Last Verified: December 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Tenofovir; Emtricitabine; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents