HIVPhase 1NCT04760691
Pre-Exposure Prophylaxis (PrEP)- Gender Affirming Hormone Therapy (GAHT) Interactions in TGW
A Phase 1 study testing Truvada alone, Truvada plus Leuprolide 11.25mg intramuscular injection and Truvada plus Estradiol 1 mg in people with HIV and Prophylaxis, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- HIV, Prophylaxis, Transgender
- What is being tested?
- Truvada alone, Truvada plus Leuprolide 11.25mg intramuscular injection and Truvada plus Estradiol 1 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2021to 24 Mar 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 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
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- 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
- Agree not to participate in other research studies involving drugs and/or medical devices for the duration of the study
Who cannot join
- 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)
- At screening or within the past 2 months: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal infection requiring treatment per current Centers for Disease Control (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. Note that HSV seropositivity with no active genital lesions is not an exclusion criterion. (Note: if an Sexually Transmitted Infection (STI) apart from HIV is detected, the participant will be referred for treatment and can be retested in 30 days and rescreened once.)
- History of an underlying clinically significant cardiac arrhythmia or renal disease (including creatinine clearance < 60 mL/min using Cockcroft-Gault equation)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins School of Medicine Drug Development Unit
Baltimore, Maryland, 21287
About this study
Official title: A Phase I Trial for the Evaluation of the Two-way Pharmacokinetic-pharmacodynamic (PD) Interaction of Gender Affirming Exogenous Estrogen (With Testosterone Suppression) on TDF/FTC PrEP in Transgender Women (TGW)
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.
Read the detailed description
The PrEP-GAHT Interactions in TGW protocol is a phase 1, open label study to compare the safety, PK and PD of five sequential phases of PrEP administration in the presence or absence of testosterone-reducing therapies or dose-escalated estrogen therapy. Each participant will undergo a Screening Visit to evaluate eligibility.
Following Baseline evaluation, eligible participants will receive 300 milligrams (mg) TDF/200 mg FTC (Truvada®) once daily for seven days, using direct observation approaches, to achieve steady state drug PrEP concentrations. After one week of therapy, participants will undergo intensive PK analysis as well as collection of colorectal biopsies for PD testing (PK1). During the PK-intensive day, iohexol will be administered intravenously for the empirical determination of renal function and measured glomerular filtration rate (mGFR). While concurrently on PrEP, participants will then be intramuscularly administered depot leuprolide acetate (11.25 mg Lupron®). Two weeks post-injection, when testosterone concentrations are far below the lower limit of normal of total testosterone in men (typically < 200 ng/dL, or < 2 ng/mL), sampling for PK, PD, and renal function will be performed (PK2).
Participants will then immediately begin low-dose oral estrogen therapy (1 mg 17β-estradiol) in conjunction with PrEP for one week, at which time samples will be collected for the analyses described above (PK3). While still on PrEP, participants will then transition to high-dose estrogen therapy (6 mg 17β-estradiol) for the remainder of the study. One week post-high dose estrogen therapy in the presence of PrEP, pharmacologic and renal samples will be collected for analysis (PK4). PrEP will then be discontinued, and two weeks later, samples will be collected to assess renal function and hormonal concentrations, and evaluate the presence of any remaining PrEP in plasma, Peripheral Blood Mononuclear Cells (PBMC), or colorectal tissue (though it should be near undetectable levels for most analytes according to the investigators' prior data)(PK5).
Safety assessments, including history/physical, chemistry/hematology labs at screening and interim history will be performed at each study-intensive visit. Additionally, periodic assessments of gender dysphoria will be conducted at baseline and a convenient time during PK visits throughout the study. To ensure compliance, participants will undergo direct observation of dosing each day of the week prior to PK visits, using the aforementioned strategies.
- Conditions
- HIV, Prophylaxis, Transgender
- Being tested
- Truvada alone, Truvada plus Leuprolide 11.25mg intramuscular injection, Truvada plus Estradiol 1 mg, Truvada plus Estradiol 6 mg, Estradiol 6 mg alone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Truvada aloneDrug
Also called tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily
Truvada plus Leuprolide 11.25mg intramuscular injectionDrug
Also called Truvada plus Lupron
TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg intramuscular injection once
Truvada plus Estradiol 1 mgDrug
Also called Truvada plus low dose estrogen
TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily
Truvada plus Estradiol 6 mgDrug
Also called Truvada plus high dose estrogen
TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Estradiol 6 mg aloneDrug
Also called Estradiol 6 mg
Estradiol 3 mg by mouth twice daily
| Study group | Role | What they receive |
|---|---|---|
| Pre-Exposure Prophylaxis (PrEP) only | Active comparator | Truvada one tablet by mouth daily Receives: 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 Receives: Drug: Truvada plus Leuprolide 11.25mg intramuscular injection |
| PrEP plus Low Dose Estrogen | Experimental | Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Receives: 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 Receives: Drug: Truvada plus Estradiol 6 mg |
| High Dose Estrogen | Experimental | Estradiol 6 mg by mouth daily x 2 weeks Receives: Drug: Estradiol 6 mg alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Maximum Tenofovir Plasma (Cmax) Concentration
Plasma TFV Cmax was defined as the highest observed concentration during the 24 hour (h) dosing interval and determined via non-compartmental analyses. Median maximum concentrations with interquartile ranges (IQR) were determined. Differences in TFV Cmax concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in TFV Cmax, with IQRs, was calculated.
Measured: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.
Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h)
The reported AUC is the area under the curve of the concentration-time curve calculated using trapezoidal rule (sum of trapezoids) over a 24h period (AUC0-24h). Median AUCs and IQRs were determined. Changes in AUC0-24h from baseline were based on comparisons between the reported AUC during each dosing period. Differences in the TFV AUC0-24h were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the TFV AUC0-24h, with IQRs, was calculated.
Measured: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.
Change in PBMC TFV-DP C24 Concentration
The PBMC TFV-DP (fmol/10^6 cells) concentration was measured at 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median PBMC TFV-DP concentrations, normalized to millions of cells analyzed, were measured. Differences in the PBMC TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the PBMC TFV-DP Concentrations, with IQRs, was calculated.
Measured: Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen.
Change in TFV-DP Colon Tissue Concentration
The estimated colon TFV-DP was measured from colon biopsies 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median colon tissue TFV-DP concentrations (with IQRs), normalized to weight of tissue biopsy analyzed, were measured. Differences in the colonic tissue TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the colonic tissue TFV-DP concentrations, with IQRs, was calculated.
Measured: Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen
Secondary outcomes (5)
Change in Serum Estradiol Concentration
The measured serum estradiol concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Differences in the serum estradiol concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum estradiol concentrations, with IQRs, was calculated.
Measured: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Free Testosterone
The measured percent free testosterone at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median percent free testosterone measurements, with interquartile range, were measured. Differences in the percent free testosterone were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in percent free testosterone, with IQRs, was calculated.
Measured: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Total Testosterone Concentration
The measured serum total testosterone concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum total testosterone concentrations, with interquartile range, were measured. Differences in serum testosterone concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum testosterone concentrations, with IQRs, was calculated.
Measured: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Luteinizing Hormone (LH) Concentration
The measured serum LH concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum LH concentrations, with interquartile range, were measured. Differences in serum LH concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum LH concentrations, with IQRs, was calculated.
Measured: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Follicle Stimulating Hormone (FSH) Concentration
The measured serum FSH concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum FSH concentrations, with interquartile range, were measured. Differences in serum FSH concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum FSH concentrations, with IQRs, was calculated.
Measured: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start1 Mar 2021
- Primary completion24 Mar 2025
- Study completion24 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark A Marzinke, PhD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760691
- Sponsor's protocol ID
- IRB00203162
- Other IDs
- R01AI145675
- Status last verified
- Apr 2026
- First submitted
- 15 Feb 2021
- Last updated
- 6 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial for the Evaluation of the Two-way Pharmacokinetic-pharmacodynamic (PD) Interaction of Gender Affirming Exogenous Estrogen (With Testosterone Suppression) on TDF/FTC PrEP in Transgender Women (TGW)
- ClinicalTrials.gov ID
- NCT04760691
- Acronym / sponsor ID
- IRB00203162
- Conditions
- HIV, Prophylaxis, Transgender
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 24 Mar 2025 (actual)
- Study completion
- 24 Mar 2025 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Posted 3 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The PrEP-GAHT Interactions in TGW protocol is a phase 1, open label study to compare the safety, PK and PD of five sequential phases of PrEP administration in the presence or absence of testosterone-reducing therapies or dose-escalated estrogen therapy. Each participant will undergo a Screening Visit to evaluate eligibility.
Following Baseline evaluation, eligible participants will receive 300 milligrams (mg) TDF/200 mg FTC (Truvada®) once daily for seven days, using direct observation approaches, to achieve steady state drug PrEP concentrations. After one week of therapy, participants will undergo intensive PK analysis as well as collection of colorectal biopsies for PD testing (PK1). During the PK-intensive day, iohexol will be administered intravenously for the empirical determination of renal function and measured glomerular filtration rate (mGFR). While concurrently on PrEP, participants will then be intramuscularly administered depot leuprolide acetate (11.25 mg Lupron®). Two weeks post-injection, when testosterone concentrations are far below the lower limit of normal of total testosterone in men (typically < 200 ng/dL, or < 2 ng/mL), sampling for PK, PD, and renal function will be performed (PK2).
Participants will then immediately begin low-dose oral estrogen therapy (1 mg 17β-estradiol) in conjunction with PrEP for one week, at which time samples will be collected for the analyses described above (PK3). While still on PrEP, participants will then transition to high-dose estrogen therapy (6 mg 17β-estradiol) for the remainder of the study. One week post-high dose estrogen therapy in the presence of PrEP, pharmacologic and renal samples will be collected for analysis (PK4). PrEP will then be discontinued, and two weeks later, samples will be collected to assess renal function and hormonal concentrations, and evaluate the presence of any remaining PrEP in plasma, Peripheral Blood Mononuclear Cells (PBMC), or colorectal tissue (though it should be near undetectable levels for most analytes according to the investigators' prior data)(PK5).
Safety assessments, including history/physical, chemistry/hematology labs at screening and interim history will be performed at each study-intensive visit. Additionally, periodic assessments of gender dysphoria will be conducted at baseline and a convenient time during PK visits throughout the study. To ensure compliance, participants will undergo direct observation of dosing each day of the week prior to PK visits, using the aforementioned strategies.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Pre-Exposure Prophylaxis (PrEP) only | Active comparator | Drug: Truvada aloneTruvada one tablet by mouth daily |
| PrEP plus Gonadotropin Releasing Hormone (GnRH) Agonist | Experimental | Drug: Truvada plus Leuprolide 11.25mg intramuscular injectionTruvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once |
| PrEP plus Low Dose Estrogen | Experimental | Drug: Truvada plus Estradiol 1 mgTruvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks |
| PrEP plus High Dose Estrogen | Experimental | Drug: Truvada plus Estradiol 6 mgTruvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks |
| High Dose Estrogen | Experimental | Drug: Estradiol 6 mg aloneEstradiol 6 mg by mouth daily x 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 18 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
Key exclusion criteria (11 listed)
- 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)
- At screening or within the past 2 months: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal infection requiring treatment per current Centers for Disease Control (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. Note that HSV seropositivity with no active genital lesions is not an exclusion criterion. (Note: if an Sexually Transmitted Infection (STI) apart from HIV is detected, the participant will be referred for treatment and can be retested in 30 days and rescreened once.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Truvada aloneAlso: tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily | Drug | Pre-Exposure Prophylaxis (PrEP) only |
| Truvada plus Leuprolide 11.25mg intramuscular injectionAlso: Truvada plus LupronTDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg intramuscular injection once | Drug | PrEP plus Gonadotropin Releasing Hormone (GnRH) Agonist |
| Truvada plus Estradiol 1 mgAlso: Truvada plus low dose estrogenTDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily | Drug | PrEP plus Low Dose Estrogen |
| Truvada plus Estradiol 6 mgAlso: Truvada plus high dose estrogenTDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily | Drug | PrEP plus High Dose Estrogen |
| Estradiol 6 mg aloneAlso: Estradiol 6 mgEstradiol 3 mg by mouth twice daily | Drug | High Dose Estrogen |
Primary outcome
Change in Maximum Tenofovir Plasma (Cmax) Concentration
Time frame: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.
Plasma TFV Cmax was defined as the highest observed concentration during the 24 hour (h) dosing interval and determined via non-compartmental analyses. Median maximum concentrations with interquartile ranges (IQR) were determined. Differences in TFV Cmax concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in TFV Cmax, with IQRs, was calculated.
Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h)
Time frame: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.
The reported AUC is the area under the curve of the concentration-time curve calculated using trapezoidal rule (sum of trapezoids) over a 24h period (AUC0-24h). Median AUCs and IQRs were determined. Changes in AUC0-24h from baseline were based on comparisons between the reported AUC during each dosing period. Differences in the TFV AUC0-24h were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the TFV AUC0-24h, with IQRs, was calculated.
Change in PBMC TFV-DP C24 Concentration
Time frame: Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen.
The PBMC TFV-DP (fmol/10^6 cells) concentration was measured at 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median PBMC TFV-DP concentrations, normalized to millions of cells analyzed, were measured. Differences in the PBMC TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the PBMC TFV-DP Concentrations, with IQRs, was calculated.
Change in TFV-DP Colon Tissue Concentration
Time frame: Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen
The estimated colon TFV-DP was measured from colon biopsies 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median colon tissue TFV-DP concentrations (with IQRs), normalized to weight of tissue biopsy analyzed, were measured. Differences in the colonic tissue TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the colonic tissue TFV-DP concentrations, with IQRs, was calculated.
5 secondary outcomes
Change in Serum Estradiol Concentration
Time frame: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Free Testosterone
Time frame: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Total Testosterone Concentration
Time frame: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Luteinizing Hormone (LH) Concentration
Time frame: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Change in Serum Follicle Stimulating Hormone (FSH) Concentration
Time frame: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Marzinke, PhD principal investigator
Johns Hopkins School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Truvada alone, Truvada plus Leuprolide 11.25mg intramuscular injection and Truvada plus Estradiol 1 mg in people with HIV and Prophylaxis, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Maximum Tenofovir Plasma (Cmax) Concentration (time frame: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.