NCT04760691

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

Completed Phase 1 Results posted Last updated 6 April 2026

What this trial tests

Phase 1 trial testing Truvada alone in HIV in 13 participants. Completed in 24 March 2025.

Timeline

1 March 2021

Primary endpoint
24 March 2025

24 March 2025

Quick facts

Lead sponsor	Johns Hopkins University
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	prevention
Enrollment	13
Start date	1 March 2021
Primary completion	24 March 2025
Estimated completion	24 March 2025
Sites	1 location across United States

Drugs / interventions tested

• Truvada alone — full drug profile →
• Truvada plus Leuprolide 11.25mg intramuscular injection
• Truvada plus Estradiol 1 mg — full drug profile →
• Truvada plus Estradiol 6 mg — full drug profile →
• Estradiol 6 mg alone — full drug profile →

Conditions studied

• HIV — all drugs for HIV →
• Prophylaxis — all drugs for Prophylaxis →
• Transgender — all drugs for Transgender →

Sponsor

Johns Hopkins University

Who can join

18 and older, male only, with HIV or Prophylaxis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Maximum Tenofovir Plasma (Cmax) Concentration Primary · 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.

Median plasma TFV Cmax (ng/mL)

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	286	274 – 358
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	276	237 – 343
PrEP Plus Low Dose Estrogen	274	231 – 331
PrEP Plus High Dose Estrogen	277	196 – 319
High Dose Estrogen	0.165	0.165 – 0.336

Median intra-individual difference TFV Cmax (ng/mL) from PrEP Only Dosing Period

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	NA	NA – NA
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-16	-32 – 57
PrEP Plus Low Dose Estrogen	-23	-63 – 47
PrEP Plus High Dose Estrogen	-27	-123 – 0.20
High Dose Estrogen	-285	-357 – -274

Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h) Primary · 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.

Median Plasma TFV are under the curve

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	2640	2578 – 3419
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	2504	2150 – 3306
PrEP Plus Low Dose Estrogen	2726	1860 – 2986
PrEP Plus High Dose Estrogen	2464	2077 – 2871
High Dose Estrogen	NA	NA – NA

Median intra-individua Difference in TFV area under the curve from PrEP Only Dosing Period

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	NA	NA – NA
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-31	-519 – 210
PrEP Plus Low Dose Estrogen	-421	-782 – -67
PrEP Plus High Dose Estrogen	-352	-902 – -67
High Dose Estrogen	NA	NA – NA

Change in PBMC TFV-DP C24 Concentration Primary · 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.

Median PBMC TFV-DP

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	59	54 – 73
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	81	66 – 100
PrEP Plus Low Dose Estrogen	94	76 – 113
PrEP Plus High Dose Estrogen	101	86 – 124
High Dose Estrogen	11	7 – 14

Median intra-individual Difference in PBMC TFV-DP from PrEP Only Dosing Period

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	NA	NA – NA
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	19	5.8 – 35
PrEP Plus Low Dose Estrogen	34	13 – 45
PrEP Plus High Dose Estrogen	41	12 – 52
High Dose Estrogen	-51	-58 – -40

Change in TFV-DP Colon Tissue Concentration Primary · 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.

Median Tissue TFV-DP

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	951	564 – 1272
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	1973	540 – 4952
PrEP Plus Low Dose Estrogen	1374	748 – 4084
PrEP Plus High Dose Estrogen	1569	400 – 3985
High Dose Estrogen	5.61	3.14 – 11.5

Median intra-individual difference in Tissue TFV-DP from PrEP Only Dosing Period

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	NA	NA – NA
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	478	-20 – 4001
PrEP Plus Low Dose Estrogen	38	-199 – 3944
PrEP Plus High Dose Estrogen	570	-13 – 2713
High Dose Estrogen	-940	-1261 – -561

Change in Serum Estradiol Concentration Secondary · 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

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.

Median Estradiol

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	21	14 – 28
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	9	6 – 10
PrEP Plus Low Dose Estrogen	17	9 – 20
PrEP Plus High Dose Estrogen	92	71 – 119
High Dose Estrogen	107	76 – 124

Median intra-individual Difference from Baseline

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	-1.6	-5.2 – 1.8
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-13	-18 – -7.3
PrEP Plus Low Dose Estrogen	-4.6	-12 – -2.6
PrEP Plus High Dose Estrogen	75	57 – 89
High Dose Estrogen	77	58 – 105

Change in Serum Free Testosterone Secondary · 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

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.

Median Free Testosterone

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	3.19	2.69 – 3.19
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	3.22	1.96 – 3.59
PrEP Plus Low Dose Estrogen	3.51	2.48 – 4.93
PrEP Plus High Dose Estrogen	3.54	3.08 – 4.63
High Dose Estrogen	3.36	2.49 – 5.18

Median intra-individual Difference from Baseline

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	-0.465	-0.675 – -0.193
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-0.585	-1.51 – -0.030
PrEP Plus Low Dose Estrogen	-0.025	-1.03 – 0.805
PrEP Plus High Dose Estrogen	-0.950	-1.08 – 1.06
High Dose Estrogen	-0.195	-0.548 – 0.883

Change in Serum Total Testosterone Concentration Secondary · 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

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.

Median Total Testosterone

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	490	396 – 554
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	151	121 – 274
PrEP Plus Low Dose Estrogen	60.5	41 – 72
PrEP Plus High Dose Estrogen	43	27 – 56
High Dose Estrogen	41	25 – 103

Median intra-individual Difference from Baseline

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	-18	-81 – 41
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-298	-346 – -219
PrEP Plus Low Dose Estrogen	-432	-510 – -320
PrEP Plus High Dose Estrogen	-448	-523 – -340
High Dose Estrogen	-445	-500 – -315

Change in Serum Luteinizing Hormone (LH) Concentration Secondary · 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

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.

Median LH

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	4.19	3.07 – 4.92
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	2.73	2.28 – 3.76
PrEP Plus Low Dose Estrogen	1.23	1.20 – 1.74
PrEP Plus High Dose Estrogen	1.60	1.15 – 3.16
High Dose Estrogen	1.66	0.76 – 2.46

Median intra-individual Difference from Baseline

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	-0.01	-0.45 – 0.69
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-1.59	-2.60 – -0.29
PrEP Plus Low Dose Estrogen	-2.37	-4.10 – -1.80
PrEP Plus High Dose Estrogen	-2.05	-3.38 – -1.32
High Dose Estrogen	-2.13	-3.52 – -0.91

Change in Serum Follicle Stimulating Hormone (FSH) Concentration Secondary · 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

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.

Median FSH

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	2.07	1.79 – 5.55
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	1.02	0.68 – 1.23
PrEP Plus Low Dose Estrogen	1.04	0.83 – 1.16
PrEP Plus High Dose Estrogen	0.56	0.41 – 0.86
High Dose Estrogen	0.34	0.25 – 0.50

Median intra-individual Difference from Baseline

Group	Value	95% CI
Pre-Exposure Prophylaxis (PrEP) Only	0.0	-0.09 – 0.30
PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist	-1.77	-4.10 – -1.0
PrEP Plus Low Dose Estrogen	-1.78	-3.85 – -0.83
PrEP Plus High Dose Estrogen	-1.86	-3.65 – -1.12
High Dose Estrogen	-2.08	-4.01 – -1.46

Adverse events — posted to ClinicalTrials.gov

Time frame: From enrollment until end of follow-up at day 56.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pre-Exposure Prophylaxis (PrEP) Only

Serious: 0/13 (0%)

Deaths: 0/13

PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist

Serious: 0/13 (0%)

Deaths: 0/13

PrEP Plus Low Dose Estrogen

Serious: 0/13 (0%)

Deaths: 0/13

PrEP Plus High Dose Estrogen

Serious: 0/13 (0%)

Deaths: 0/13

High Dose Estrogen

Serious: 0/13 (0%)

Deaths: 0/13

Other adverse events (4 terms — click to expand)

Reaction	System	Pre-Exposure Prophylaxis (…	PrEP Plus Gonadotropin Rel…	PrEP Plus Low Dose Estrogen	PrEP Plus High Dose Estrogen	High Dose Estrogen
Low phosphorus	Investigations	—	—	—	—	—
Low eGFR	Investigations	—	—	—	—	—
Nausea and vomitting	Gastrointestinal disorders	—	—	—	—	—
Calf muscle pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—

Data from ClinicalTrials.gov NCT04760691 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.