Pre-Exposure Prophylaxis (PrEP)- Gender Affirming Hormone Therapy (GAHT) Interactions in TGW

NCT04760691 | Completed Phase 1 FDA Drug

• 2 other identifiers: IRB00203162R01AI145675
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to determine the best way to dose Truvada®, an oral medication licensed to be taken as Pre-Exposure Prophylaxis (PrEP) to prevent HIV infection, in transgender women who are also taking feminizing hormones. The duration of the study is about 4 months, and involves a screening visit, a baseline visit with colon biopsies and kidney function testing, and several outpatient visits, including 5 intensive sampling visits that last about 9 hours and involve colon biopsies, kidney function testing and other blood specimen collections. After the baseline visit, participants will start on PrEP, daily Truvada® pills, and will continue on the Truvada® for 5 weeks. Participants will then receive either an injection of Lupron, oral low-dose estradiol or oral high-dose estradiol, which will be taken along with the Truvada® PrEP for 1-2 weeks before returning for an intensive sampling visit.

Conditions

Hiv; Prophylaxis; Transgender

Outcome Measures

Primary Outcomes (3)

• Change in Tenofovir plasma concentration

  Change in Tenofovir plasma concentration measured in nanograms (ng) per milliliter (mL)

  Days 7-8, Days 21-22, Days 28-29, Days 35-36, Days 49-50

• Change in Tenofovir-Diphosphate PBMC concentration

  Change in tenofovir-diphosphate (TFV-DP) PBMC concentration reported in femtomoles per million cells (fmol/million)

  Days 7-8, Days 21-22, Days 28-29, Days 35-36, Days 49-50

• Change in TFV-DP colon tissue concentration

  Change in TFV-DP colon tissue concentration reported in fmol/million

  Days 7-8, Days 21-22, Days 28-29, Days 35-36, Days 49-50

Secondary Outcomes (5)

• Change in serum estradiol concentration

  Days 7, 21, 28, 35, 49

• Change in serum free testosterone concentration

  Days 7, 21, 28, 35, 49

• Change in serum total testosterone concentration

  Days 7, 21, 28, 35, 49

• Change in Serum luteinizing hormone (LH) concentration

  Days 7, 21, 28, 35, 49

• Change in serum follicular stimulating hormone (FSH)

  Days 7, 21, 28, 35, 49

Study Arms (5)

Pre-Exposure Prophylaxis (PrEP) only

ACTIVE COMPARATOR

Truvada one tablet by mouth daily

Drug: Truvada alone

PrEP plus Gonadotropin Releasing Hormone (GnRH) Agonist

EXPERIMENTAL

Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once

Drug: Truvada plus Leuprolide

PrEP plus Low Dose Estrogen

EXPERIMENTAL

Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks

Drug: Truvada plus Estradiol 1 mg

PrEP plus High Dose Estrogen

EXPERIMENTAL

Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks

Drug: Truvada plus Estradiol 6 mg

High Dose Estrogen

EXPERIMENTAL

Estradiol 6 mg by mouth daily x 2 weeks

Drug: Estradiol 6 mg alone

Interventions

Truvada alone DRUG

TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily

Also known as: tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)

Pre-Exposure Prophylaxis (PrEP) only

Truvada plus Leuprolide DRUG

TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im once

Also known as: Truvada plus Lupron

PrEP plus Gonadotropin Releasing Hormone (GnRH) Agonist

Truvada plus Estradiol 1 mg DRUG

TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily

Also known as: Truvada plus low dose estrogen

PrEP plus Low Dose Estrogen

Truvada plus Estradiol 6 mg DRUG

TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twie daily

Also known as: Truvada plus high dose estrogen

PrEP plus High Dose Estrogen

Estradiol 6 mg alone DRUG

Estradiol 3 mg by mouth twice daily

Also known as: Estradiol 6 mg

High Dose Estrogen

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: transgender women (biologic sex identified male at birth; identifying as female)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Self-identifying as a transgender woman
• Not currently taking any gender affirming hormonal therapy (GAHT) with a total testosterone concentration of ≥ 200 ng/dL, or willing to abstain from feminizing therapies (including estradiol, spironolactone, progesterone, etc.) until total total testosterone concentrations are ≥ 200 ng/dL. Note: Testosterone may be retested every 2-4 weeks during screening to determine eligibility up to 6 weeks.
• HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay
• Understand and agree to local STI reporting requirements
• Able and willing to communicate in English
• Able and willing to provide written informed consent to take part in the study
• Able and willing to provide adequate information for locator purposes
• Able and willing to participate in a directly observed study, which may occur in person, using live streaming or a time stamped video?
• Availability to return for all study visits, barring unforeseen circumstances
• Willing to abstain from insertion of anything (drug, enema, penis, or sex toy) in rectum for 72 hours before and 72 hours after each flexible sigmoidoscopy
• Willing to refrain from aspirin and NSAID use for one week before and after each study biopsy visit
• Willing and able to use condoms for all Receptive Anal Intercourse (RAI) for the duration of participation
• Willing and able to participate in a directly observed study, which may occur in person, using live streaming or a time stamped video
• Has an identified healthcare provider for transgender health management

You may not qualify if:

• Not currently on any PrEP regimen (e.g., Truvada®, tenofovir alafenamide/ emtricitabine)
• History of chronic Hepatitis B infection, as documented by positive HBsAg at screening
• ≥ Grade 2 laboratory abnormality at baseline as defined by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 - July 2017, and Addendum 3 (Rectal Grading Tables for Use in Microbicide Studies)
• Significant colorectal symptom(s) as determined by medical history or by participant self- report (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, history of inflammatory bowel disease, presence of symptomatic hemorrhoids, and presence of any painful anorectal conditions that would be tender to manipulation)
• History of an underlying clinically significant cardiac arrhythmia or renal disease (including creatinine clearance \< 60 mL/min using Cockcroft-Gault equation)
• Serum phosphate \< 2.3 mg/dL
• History of severe or recent cardiac or pulmonary event
• History of significant gastrointestinal bleeding
• Current use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin \[\>81 mg\], Non-steroidal anti-inflammatory drug \[NSAIDs\], or Pradaxa®)
• Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment or planned use at any time during study participation

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Johns Hopkins School of Medicine Drug Development Unit

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine; Leuprolide; Estradiol; Estrogens; Single Person

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)

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; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Officials

• Mark A Marzinke, PhD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: February 18, 2021
• Study Start: March 1, 2021
• Primary Completion: March 24, 2025
• Study Completion: March 24, 2025
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)