HIV I InfectionPhase 2GETITRIgHTNCT06005610
Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy
A Phase 2 study testing Estradiol in people with HIV I Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in 4 countries.
Trial summary
Transgender women (TW) are a key population and priority for HIV treatment. More research is needed to develop evidence-based clinical guidance when it comes to choosing antiretroviral treatment (ART) regimens for TW on feminizing hormonal therapy (FHT). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- HIV I Infection
- What is being tested?
- Estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 4 Jan 2024to 21 Aug 2025
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documentation of HIV-1 status.
- On ART for at least 24 weeks prior to study entry. Regimen changes within the 24 weeks prior to study entry are acceptable, but candidates must have been on a stable regimen for at least 28 days prior to study entry.
- On BIC/FTC/TAF, DTG/TDF/FTC or 3TC, or DRV/c-containing ART for at least 28 days prior to study entry (single tablet regimen not required), and with no plans to change ART regimen over the study duration of 48 weeks.
- Desire to initiate or restart FHT, regardless of orchiectomy status.
- HIV-1 RNA <200 copies/mL at screening.
- HIV-1 RNA <400 copies/mL available through routine clinical care between 24 and 96 weeks prior to study entry and while on ART. The HIV-1 RNA must be the most recent value obtained between 24 and 96 weeks prior to study entry.
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- The following laboratory values obtained within 60 days prior to study entry
- Hemoglobin ≥9.0 g/dL
- Platelet count ≥75,000/mm3
- Estimated Glomerular Filtration Rate (eGFR) ≥30 mL/min/1.73m2 if on or switching to TAF, ≥50 mL/min/1.73m2 if on or switching to TDF without cobicistat, or ≥70 mL/min/1.73m2 if on or switching to TDF in combination with cobicistat, calculated using standardized equation for eGFR
- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase are within normal range per local laboratory range
- Prolactin <25 ng/dL
- Serum estradiol level <75 pg/mL within 60 days prior to study entry.
- Willingness to avoid the use of prescribed, non-study provided FHT and non-prescribed FHT during the study period, and no planned use of prescribed or non-prescribed anti-androgens for the first 24 weeks of the study.
- Ability and willingness of participant to provide informed consent and ability and willingness of participant to undergo study procedures.
Who cannot join
- Known clotting disorders, active deep vein thrombosis (DVT), pulmonary embolism (PE), or history of these conditions, active arterial thromboembolic disease (e.g., stroke, myocardial infarction), or history of these conditions.
- Known liver impairment or disease.
- History of chronic hepatitis B virus (HBV) infection or active HBV infection.
- History of current active hepatitis C virus (HCV) infection.
- Prohibited medication use (including drugs with known or expected DDIs with FHT or ART) at time of study entry.
- Receipt of any estrogen therapy within 14 days prior to study entry for persons on oral FHT, or within 30 days prior to entry for persons on injectable FHT.
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- Known HIV-1 resistance mutations that would preclude remaining on current ART or a switch to a study regimen, in the opinion of the site investigator.
- Personal history of breast cancer. or known personal history of breast cancer (BRCA) gene.
- Known or a history of testicular cancer.
- Known or a history of gall bladder disease.
- Known or suspected pituitary adenoma.
- Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
- Suicidal ideation in the past 30 days or suicide attempt in the past 90 days, as reported on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry. Stable (in the opinion of the site investigator) treatments for chronic comorbidities are allowed.
- Presence of any other medical condition that would preclude FHT administration for safety reasons, in the opinion of the site investigator.
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
United States14 sites
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, 30308
University of Colorado Hospital CRS (6101)
Aurora, Colorado, 80045
Johns Hopkins University CRS (201)
Baltimore, Maryland, 21205
Chapel Hill CRS (3201)
Chapel Hill, North Carolina, 27599-7215
Case CRS (2501)
Cleveland, Ohio, 44106
Greensboro CRS (3203)
Greensboro, North Carolina, 27401
Houston AIDS Research Team CRS (31473)
Houston, Texas, 77030
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, 37204
Weill Cornell Uptown CRS (site 7803)
New York, New York, 10065
New Jersey Medical School Clinical Research Center CRS (31786)
Newark, New Jersey, 07103
UCSD Antiviral Research Center CRS (701)
San Diego, California, 92103
University of California, San Francisco HIV/AIDS CRS (801)
San Francisco, California, 94110
Washington University Therapeutics (WT) CRS (2101)
St Louis, Missouri, 63110-1010
Whitman-Walker Institute, Inc. CRS (31791)
Washington D.C., District of Columbia, 20005
Thailand2 sites
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (31802)
Bangkok, Patumwan, 10330
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (31784)
Chiang Mai, 50200
About this study
Official title: Giving Standardized Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy
Transgender women (TW) are a key population and priority for HIV treatment. More research is needed to develop evidence-based clinical guidance when it comes to choosing antiretroviral treatment (ART) regimens for TW on feminizing hormonal therapy (FHT). Concerns about ART interacting with FHT and decreasing its effectiveness can lead to decreased ART adherence and increased viral loads. Prior data suggest that access to FHT improves adherence to HIV treatment and decreases treatment interruptions.
The Giving Standardized Estradiol Therapy In Transgender Women to Research Interactions with HIV Therapy (GET IT RiGHT) trial aimed to address concerns about drug-drug interactions (DDIs) between ART and FHT while providing access to hormonal therapy to TW living with HIV.
Read more
This was an open-label, non-randomized, 3-group trial of adult TW and other individuals identifying as female or transfeminine but with male sex assigned at birth living with HIV. Participants were on ART at entry and received study-supplied 17-β estradiol for FHT for up to 48 weeks.
The primary objectives of the study were to 1) assess whether TW continue to achieve therapeutic concentrations of ART while receiving FHT for 48 weeks and 2) assess whether serum estradiol concentrations on FHT (across a range of estradiol doses) vary between boosted and un-boosted ART regimens.
Read the detailed description
A5403 was a phase 2b, 48-week, open-label, non-randomized, 3-group trial, of 90 adult (≥18 years) transgender women and other individuals identifying as female or transfeminine but with male sex assigned at birth (TW) living with HIV on suppressive antiretroviral therapy (ART) and not currently on FHT. The trial aimed to enroll at least 50% participants who identified as non-white or Latine.
The trial consisted of three groups, a bictegravir (BIC)-treated group (BIC/TAF/FTC; n=30 accrual target for evaluable participants) (Group 1), a dolutegravir (DTG)-treated group (DTG/TDF/FTC or 3TC; n=30 accrual target for evaluable participants) (Group 2), and a boosted darunavir (DRV)-treated group (DRV/c; n=30 accrual target for evaluable participants) (Group 3), for a total accrual target of 90 participants evaluable for pharmacokinetic (PK) analyses.
All participants continued ART (not provided by the trial) and received study-supplied 17-β estradiol for weeks 0-48. At entry, participants were assigned to one of the three analysis groups based on their current ART regimen. Participants on other ART regimens at screening who were willing to switch to one of the regimens above were also eligible to enroll.
All participants received study supplied 17-β estradiol for weeks 0-48. Oral 17-β estradiol 2 mg once daily was initiated following study entry. At weeks 4, 12, 24, and 36, study clinicians could titrate 17-β estradiol in 2 mg increments as described in the protocol.
Intensive PK subgroup (n=15 per ART group): At entry (week 0), an 8-hour intensive PK sampling assessed ART exposure prior to FHT initiation. At week 24, intensive sampling was repeated to assess 17-β estradiol and ART exposure. A final intensive PK visit occurred at week 48 to assess 17-β estradiol and ART exposure at the maximal FHT dosing achieved during the study period.
Sparse PK sampling: all participants not participating in an intensive PK sampling visit on the same day had timed, sparse PK sampling collected at each visit to characterize the trough plasma (BIC, DTG, and DRV) and intracellular ART (Tenofovir diphosphate (TFV-DP), emtricitabine triphosphate (FTC-TP), and lamivudine triphosphate (3TC-TP)), concentrations to evaluate the relationship of ART PK exposure across a range of 17-β estradiol doses.
To measure acceptability, participants were asked to self-report the degree to which they found the intervention appropriate and useful using Likert-type agreement scales at three study time points: entry, 24 weeks, and 48 weeks. To measure satisfaction, the 12-question Transgender Congruence Scale (TCS) was used, which assessed associations between gender-affirming treatments, perceived gender congruence, and satisfaction at three study time points: entry, 24 weeks, and 48 weeks.
Other assessments during study participation included: anthropometric measurements (including weight, height, minimum waist circumference, and maximum hip circumference), routine chemistry and hematology labs, HIV-1 viral load in plasma, CD4+ and CD8+ T cell counts and percentages, lipids, glucose and insulin, non-estradiol hormone concentrations, stored Peripheral Blood Mononuclear Cells (PBMC), plasma, and serum, and ART and FHT adherence assessments.
Planned individual interviews with a subset of participants for further information on intervention satisfaction and acceptability were not conducted.
In May 2025, the sponsor, the Division of AIDS (DAIDS) at NIAID, sent notice that the trial was terminated. Participants still in follow-up were contacted to schedule a final, premature discontinuation visit where transition of estradiol management and procurement to local care could be arranged. Additionally, funding to perform batched retrospective lab testing for pharmacokinetics (primary and some secondary outcomes) and insulin testing (secondary outcome) was unavailable.
- Conditions
- HIV I Infection
- Being tested
- Estradiol
- Keywords
- HIV, Transgender women, Estradiol, ART, Drug interactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Oral 17-β estradiol 2 mg once daily initiated immediately following entry. At weeks 4, 12, 24, and 36, study clinicians may have titrated 17-β estradiol in 2 mg increments to achieve the desired participant goals and target hormone concentrations, as measured locally at each visit.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Estradiol among BIC-treated | Experimental | Participants taking bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC) who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. Receives: Drug: Estradiol |
| Group 2: Estradiol among DTG-treated | Experimental | Participants taking dolutegravir (DTG) once daily + tenofovir disoproxil fumarate (TDF) + (FTC or lamivudine [3TC]), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. Receives: Drug: Estradiol |
| Group 3: Estradiol among DRV/c-treated | Experimental | Participants taking any anti-retroviral treatment regimen containing darunavir plus cobicistat (DRV/c), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Ratio of Antiretroviral Treatment (ART) Analytes Bictegravir (BIC), Dolutegravir (DTG), and Darunavir (DRV) Trough Concentrations (Ctrough) in Plasma at Each Received Dose of Oral 17-β Estradiol
Log-transformed trough concentrations (Ctrough) in ng/mL of the analytes BIC, DTG, and DRV from plasma samples collected 22-26 hours post ART dose, measured over 48 weeks. Geometric ratios will be calculated as the log of Ctrough of the ART analyte at each dose of 17-β estradiol - log of Ctrough of that same ART analyte at baseline. If multiple observations are available at the same estradiol dose, the first sampled qualifying steady-state trough concentration (based on calendar time) taken will be used.
Measured: Study Entry and Weeks 4, 12, 24, 36, and 48
Percentage of Participants With ART Analyte Trough Concentration (Ctrough) Above Drug-specific Threshold
Trough concentration of the analytes BIC, DTG, and DRV in plasma at each received dose of 17-β estradiol summarized at the participant level as indicator of concentration being above drug-specific threshold.
Measured: Study Entry and Weeks 4, 12, 24, 36, and 48
Trough Serum Total Estradiol Assessed at Each Received Dose of Oral 17-β Estradiol as Quantified Via Batch Testing at Central Lab.
Trough concentrations of Total 17-β estradiol in ng/mL from serum samples collected 22-26 hours post 17-β estradiol dose. Results < Lower Limit of Quantification (LLoQ) at entry will be imputed as 0 ng/mL at one-half the LLoQ value at visits post-entry. If multiple observations are available at the same estradiol dose, the first qualifying trough concentration (based on time since last dose) taken will be used.
Measured: Study Entry and Weeks 4, 12, 24, 36, and 48
Secondary outcomes (24)
Geometric Ratio of Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) in Non-viable Peripheral Blood Mononuclear Cells (PBMCs) at Each Received Dose of Oral 17-β Estradiol
Log-transformed trough concentrations (Ctrough) in ng/mL of the metabolites of the following drugs: TFV-DP, FTC-TP, and 3TC-TP from PBMC samples collected 22-26 hours post antiretroviral treatment (ART) dose, measured over 48 weeks. Geometric ratios will be calculated as the log of Ctrough of the ART analyte at each dose of 17-β estradiol - log of Ctrough of that same ART analyte at entry. If multiple observations are available at the same estradiol dose, the first sampled qualifying steady-state trough concentration (based on calendar time) taken will be used.
Measured: Study Entry and Weeks 4, 12, 24, 36 and 48
Percentage of Participants With Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) Trough Concentration Above Drug-specific Threshold
Trough concentration of the analytes TFV-DP, FTC-TP, and 3TC-TP in non-viable PBMCs at each received dose of 17-β estradiol summarized at the participant level as indicator of concentration being above drug-specific externally defined threshold.
Measured: Study Entry and Weeks 4, 12, 24, 36 and 48
Percentage of Participants With an Occurrence of Any Reportable Adverse Event Related to 17-β Estradiol
Reportable Adverse events included the following: all new diagnoses, signs/symptoms and laboratory events of ≥Grade 3; events that led to an interruption or dose reduction of estradiol regardless of grade; all serious adverse events (SAEs) ; ≥ grade 1 lipid and glucose abnormalities; ≥ grade 2 cholecystitis, elevated liver enzymes or hypertension; and all cases of cardiovascular disease (CVD), cancer, diabetes or pre-diabetes and any vascular events were reported. Division of AIDS Adverse Events Grading Table (V2.1) was used. Relatedness to 17-β estradiol determined by local site research personnel.
Measured: Treatment initiation to Week 48
Percentage of Participants With an Occurrence of Any Targeted Adverse Event
Targeted adverse events included the following: Serious Adverse Events (SAEs), coronary heart disease or other cardiovascular disease, cancer (exclusive of basal/squamous cell skin cancer), diabetes or pre-diabetes and any vascular events (including arterial events (strokes and myocardial infarctions) or deep venous thrombotic events (venous thromboembolism, deep venous thrombosis, retinal vein thrombosis, and pulmonary embolism).
Measured: Treatment initiation to Week 48
Percentage of Participants With Serum Total Testosterone < 50 ng/dL at Each Received Dose of Oral 17-β Estradiol
Results < lower limit of quantification will be considered to be <50 ng/dL. If multiple observations are available at the same estradiol dose, the last testosterone concentration (based on calendar time) will be used.
Measured: Study entry to week 48
Percentage of Participants With Virologic Suppression of HIV
Virologic suppression of HIV is defined as plasma HIV-1 viral load <50 copies/mL.
Measured: Study entry and weeks 12, 24,36 and 48
Absolute Changes in Overall Transgender Congruence Score (TCS)
The overall transgender congruence score is calculated from participant response to the 12-question Transgender Congruence Scale (TCS). Participants rate each item on a 5-point Likert-type scale (i.e., 1 = strongly disagree, 2 = somewhat disagree, 3 = neither agree nor disagree, 4 = somewhat agree, 5 = strongly agree). Questions 'The way my body currently looks does not represent my gender identity.', 'I do not feel that my appearance reflects my gender identity.', and 'I am not proud of my gender identity.' are reversed scored. The overall score is the average of the response to the 12 questions, with higher scores indicating a higher level of congruence. Positive changes from baseline indicate improvement in transgender congruence.
Measured: Study entry to weeks 24, and 48
Area Under the Curve Over 8 Hours (AUC 0-8h) of 17-β Estradiol
From pre-dose, 1, 2, 3, 4, 6, and 8 hours post dosing at entry and weeks 24 and 48.
The AUC will use the linear up/log down version of the trapezoidal rule in non-compartmental analysis using software called Phoenix WinNonLin (Certara®). This version of the trapezoidal rule uses linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast.
Measured: Study entry and Weeks 24, and 48
Percent Change in Weight
Calculated by dividing weight in kilograms at later time point minus weight at study entry by weight at study entry, and then multiplying by 100.
Measured: Study entry to weeks 4,12, 24, 36, and 48
Percent Change in Body Mass Index (BMI)
Calculated by dividing BMI at later time point minus BMI at study entry by BMI at study entry, and then multiplying by 100.
Measured: Study entry and weeks 4, 12, 24, 36, and 48
Absolute Change in Minimum Waist Circumference
Calculated as waist circumference (centimeters or cm) at later time point minus waist circumference at study entry. Measurements taken on bare skin at the smallest horizontal circumference above the umbilicus and below the xiphoid process. Tape was level and parallel to the floor, and participant's arms were at their sides and their feet and ankles were together. Measurements taken at the end of the participant's normal, relaxed exhalation. Measurements taken in triplicate and averaged. Measurement rounded to nearest tenth of a centimeter. If one value was more than 10% different than the other two values, it was discarded, and the remaining two values were averaged.
Measured: Study entry and weeks 4,12, 24, 36, and 48
Absolute Change in Maximum Hip Circumference
Calculated as maximum hip circumference (in centimeters or cm) at later time point minus maximum hip circumference at study entry.
Measured: Study entry and weeks 4, 12, 24, 36, and 48
Absolute Change in Waist-hip Ratio (WHR) Measured
Calculated as waist-hip ratio (WHR) at later time point minus waist-hip ratio at study entry.
Measured: Study entry and weeks 4,12, 24, 36, and 48
Absolute Changes in Fasting High-density Lipoprotein Cholesterol (HDL)
Calculated as fasting high-density lipoprotein cholesterol (HDL in milligrams per deciliter or mg/dL) at later time point minus fasting HDL at study entry.
Measured: Study entry and weeks 12, 24, and 48
Absolute Changes in Fasting Blood Glucose (FBG)
Calculated as fasting glucose result (or FBG in milligrams/deciliter or mg/dL) at later time point minus fasting blood glucose (FBG) at study entry.
Measured: Study entry to weeks 4,12, 24, 36, and 48
Absolute Changes in Insulin Sensitivity
Calculated as insulin sensitivity at later time point minus insulin sensitivity at study entry. Insulin will be measured from stored samples. Insulin sensitivity will be calculated as Homeostatic Model Assessment of Insulin Resistance model (HOMA-IR) = (fasting glucose in mmol/L * fasting insulin in µU/L) /22.5.
Measured: Study entry and weeks 12, 24, 36, and 48
Absolute Changes in Fasting Triglycerides (TRG)
Calculated as fasting triglycerides (TRG in milligrams per deciliter or mg/dL) at later time point minus fasting TRG at study entry.
Measured: Study entry to weeks 12, 24, and 48
Absolute Changes in Fasting Total Cholesterol (CHOL)
Calculated as fasting total cholesterol (CHOL in milligrams per deciliter or mg/dL) at later time point minus fasting CHOL at study entry.
Measured: Study entry to weeks 12, 24, and 48
Absolute Changes in Fasting Direct Low-density Lipoprotein Cholesterol (LDL)
Calculated as fasting direct low-density lipoprotein cholesterol (LDL in milligrams per deciliter or mg/dL) at later time point minus fasting LDL at study entry.
Measured: Study entry to weeks 12, 24, and 48
Absolute Change in Weight
Calculated as weight in kilograms (kg) at follow-up time minus weight at study entry.
Measured: Study entry to weeks 4,12, 24, 36, and 48
Absolute Change in Body Mass Index (BMI)
Calculated as BMI (in kg/m^2) at follow-up time minus BMI at study entry.
Measured: Study entry to weeks 4, 12, 24, 36, and 48
Percent Change in Minimum Waist Circumference
Calculated by dividing waist circumference (centimeters or cm) at later time point minus waist circumference by waist circumference study entry, and then multiplying by 100.
Measured: Study entry and weeks 4,12, 24, 36, and 48
Percent Change in Maximum Hip Circumference
Calculated by dividing hip circumference (in centimeters or cm) at later time point minus maximum hip circumference at study entry by hip circumference at entry, and then multiplying by 100.
Measured: Study entry and weeks 4, 12, 24, 36, and 48
Percent Change in Waist-hip Ratio (WHR) Measured
Calculated by dividing waist-hip ratio (WHR) at later time point minus waist-hip ratio at study entry by waist-hip ratio at entry, and then multiplying by 100.
Measured: Study entry and weeks 4,12, 24, 36, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2023
- Study start4 Jan 2024
- Primary completion21 Aug 2025
- Study completion21 Aug 2025
Why it stopped: Trial terminated by Sponsor.
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 HIV I InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jordan E. Lake, MD, MSc, Study chair, Houston AIDS Research Team CRSKimberly K. Scarsi, PharmD, MS, FCCP, Study chair, University of NebraskaJorge A. Gallardo-Cartagena, MD, Study chair, Barranco CRS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06005610
- Sponsor's protocol ID
- A5403
- Other IDs
- 38806
- Acronym
- GETITRIgHT
- Status last verified
- Mar 2026
- First submitted
- 15 Aug 2023
- Last updated
- 8 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Giving Standardized Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy
- ClinicalTrials.gov ID
- NCT06005610
- Acronym / sponsor ID
- GETITRIgHT / A5403
- Conditions
- HIV I Infection
- Keywords
- HIV, Transgender women, Estradiol, ART, Drug interactions
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial terminated by Sponsor.
- Enrolment
- 93 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 4 Jan 2024 (actual)
- Primary completion
- 21 Aug 2025 (actual)
- Study completion
- 21 Aug 2025 (actual)
- First posted
- 22 Aug 2023 (actual)
- Results
- Posted 8 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transgender women (TW) are a key population and priority for HIV treatment. More research is needed to develop evidence-based clinical guidance when it comes to choosing antiretroviral treatment (ART) regimens for TW on feminizing hormonal therapy (FHT). Concerns about ART interacting with FHT and decreasing its effectiveness can lead to decreased ART adherence and increased viral loads. Prior data suggest that access to FHT improves adherence to HIV treatment and decreases treatment interruptions.
The Giving Standardized Estradiol Therapy In Transgender Women to Research Interactions with HIV Therapy (GET IT RiGHT) trial aimed to address concerns about drug-drug interactions (DDIs) between ART and FHT while providing access to hormonal therapy to TW living with HIV.
This was an open-label, non-randomized, 3-group trial of adult TW and other individuals identifying as female or transfeminine but with male sex assigned at birth living with HIV. Participants were on ART at entry and received study-supplied 17-β estradiol for FHT for up to 48 weeks.
The primary objectives of the study were to 1) assess whether TW continue to achieve therapeutic concentrations of ART while receiving FHT for 48 weeks and 2) assess whether serum estradiol concentrations on FHT (across a range of estradiol doses) vary between boosted and un-boosted ART regimens.
Detailed description
A5403 was a phase 2b, 48-week, open-label, non-randomized, 3-group trial, of 90 adult (≥18 years) transgender women and other individuals identifying as female or transfeminine but with male sex assigned at birth (TW) living with HIV on suppressive antiretroviral therapy (ART) and not currently on FHT. The trial aimed to enroll at least 50% participants who identified as non-white or Latine.
The trial consisted of three groups, a bictegravir (BIC)-treated group (BIC/TAF/FTC; n=30 accrual target for evaluable participants) (Group 1), a dolutegravir (DTG)-treated group (DTG/TDF/FTC or 3TC; n=30 accrual target for evaluable participants) (Group 2), and a boosted darunavir (DRV)-treated group (DRV/c; n=30 accrual target for evaluable participants) (Group 3), for a total accrual target of 90 participants evaluable for pharmacokinetic (PK) analyses.
All participants continued ART (not provided by the trial) and received study-supplied 17-β estradiol for weeks 0-48. At entry, participants were assigned to one of the three analysis groups based on their current ART regimen. Participants on other ART regimens at screening who were willing to switch to one of the regimens above were also eligible to enroll.
All participants received study supplied 17-β estradiol for weeks 0-48. Oral 17-β estradiol 2 mg once daily was initiated following study entry. At weeks 4, 12, 24, and 36, study clinicians could titrate 17-β estradiol in 2 mg increments as described in the protocol.
Intensive PK subgroup (n=15 per ART group): At entry (week 0), an 8-hour intensive PK sampling assessed ART exposure prior to FHT initiation. At week 24, intensive sampling was repeated to assess 17-β estradiol and ART exposure. A final intensive PK visit occurred at week 48 to assess 17-β estradiol and ART exposure at the maximal FHT dosing achieved during the study period.
Sparse PK sampling: all participants not participating in an intensive PK sampling visit on the same day had timed, sparse PK sampling collected at each visit to characterize the trough plasma (BIC, DTG, and DRV) and intracellular ART (Tenofovir diphosphate (TFV-DP), emtricitabine triphosphate (FTC-TP), and lamivudine triphosphate (3TC-TP)), concentrations to evaluate the relationship of ART PK exposure across a range of 17-β estradiol doses.
To measure acceptability, participants were asked to self-report the degree to which they found the intervention appropriate and useful using Likert-type agreement scales at three study time points: entry, 24 weeks, and 48 weeks. To measure satisfaction, the 12-question Transgender Congruence Scale (TCS) was used, which assessed associations between gender-affirming treatments, perceived gender congruence, and satisfaction at three study time points: entry, 24 weeks, and 48 weeks.
Other assessments during study participation included: anthropometric measurements (including weight, height, minimum waist circumference, and maximum hip circumference), routine chemistry and hematology labs, HIV-1 viral load in plasma, CD4+ and CD8+ T cell counts and percentages, lipids, glucose and insulin, non-estradiol hormone concentrations, stored Peripheral Blood Mononuclear Cells (PBMC), plasma, and serum, and ART and FHT adherence assessments.
Planned individual interviews with a subset of participants for further information on intervention satisfaction and acceptability were not conducted.
In May 2025, the sponsor, the Division of AIDS (DAIDS) at NIAID, sent notice that the trial was terminated. Participants still in follow-up were contacted to schedule a final, premature discontinuation visit where transition of estradiol management and procurement to local care could be arranged. Additionally, funding to perform batched retrospective lab testing for pharmacokinetics (primary and some secondary outcomes) and insulin testing (secondary outcome) was unavailable.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Estradiol among BIC-treated | Experimental | Drug: EstradiolParticipants taking bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC) who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. |
| Group 2: Estradiol among DTG-treated | Experimental | Drug: EstradiolParticipants taking dolutegravir (DTG) once daily + tenofovir disoproxil fumarate (TDF) + (FTC or lamivudine [3TC]), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. |
| Group 3: Estradiol among DRV/c-treated | Experimental | Drug: EstradiolParticipants taking any anti-retroviral treatment regimen containing darunavir plus cobicistat (DRV/c), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Documentation of HIV-1 status.
- On ART for at least 24 weeks prior to study entry. Regimen changes within the 24 weeks prior to study entry are acceptable, but candidates must have been on a stable regimen for at least 28 days prior to study entry.
- On BIC/FTC/TAF, DTG/TDF/FTC or 3TC, or DRV/c-containing ART for at least 28 days prior to study entry (single tablet regimen not required), and with no plans to change ART regimen over the study duration of 48 weeks.
- Desire to initiate or restart FHT, regardless of orchiectomy status.
- HIV-1 RNA <200 copies/mL at screening.
Key exclusion criteria (15 listed)
- Known clotting disorders, active deep vein thrombosis (DVT), pulmonary embolism (PE), or history of these conditions, active arterial thromboembolic disease (e.g., stroke, myocardial infarction), or history of these conditions.
- Known liver impairment or disease.
- History of chronic hepatitis B virus (HBV) infection or active HBV infection.
- History of current active hepatitis C virus (HCV) infection.
- Prohibited medication use (including drugs with known or expected DDIs with FHT or ART) at time of study entry.
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 |
|---|---|---|
| EstradiolOral 17-β estradiol 2 mg once daily initiated immediately following entry. At weeks 4, 12, 24, and 36, study clinicians may have titrated 17-β estradiol in 2 mg increments to achieve the desired participant goals and target hormone concentrations, as measured locally at each visit. | Drug | Group 1: Estradiol among BIC-treated, Group 2: Estradiol among DTG-treated, Group 3: Estradiol among DRV/c-treated |
Primary outcome
Geometric Ratio of Antiretroviral Treatment (ART) Analytes Bictegravir (BIC), Dolutegravir (DTG), and Darunavir (DRV) Trough Concentrations (Ctrough) in Plasma at Each Received Dose of Oral 17-β Estradiol
Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48
Log-transformed trough concentrations (Ctrough) in ng/mL of the analytes BIC, DTG, and DRV from plasma samples collected 22-26 hours post ART dose, measured over 48 weeks. Geometric ratios will be calculated as the log of Ctrough of the ART analyte at each dose of 17-β estradiol - log of Ctrough of that same ART analyte at baseline. If multiple observations are available at the same estradiol dose, the first sampled qualifying steady-state trough concentration (based on calendar time) taken will be used.
Percentage of Participants With ART Analyte Trough Concentration (Ctrough) Above Drug-specific Threshold
Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48
Trough concentration of the analytes BIC, DTG, and DRV in plasma at each received dose of 17-β estradiol summarized at the participant level as indicator of concentration being above drug-specific threshold.
Trough Serum Total Estradiol Assessed at Each Received Dose of Oral 17-β Estradiol as Quantified Via Batch Testing at Central Lab.
Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48
Trough concentrations of Total 17-β estradiol in ng/mL from serum samples collected 22-26 hours post 17-β estradiol dose. Results < Lower Limit of Quantification (LLoQ) at entry will be imputed as 0 ng/mL at one-half the LLoQ value at visits post-entry. If multiple observations are available at the same estradiol dose, the first qualifying trough concentration (based on time since last dose) taken will be used.
24 secondary outcomes
Geometric Ratio of Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) in Non-viable Peripheral Blood Mononuclear Cells (PBMCs) at Each Received Dose of Oral 17-β Estradiol
Time frame: Study Entry and Weeks 4, 12, 24, 36 and 48
Percentage of Participants With Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) Trough Concentration Above Drug-specific Threshold
Time frame: Study Entry and Weeks 4, 12, 24, 36 and 48
Percentage of Participants With an Occurrence of Any Reportable Adverse Event Related to 17-β Estradiol
Time frame: Treatment initiation to Week 48
Percentage of Participants With an Occurrence of Any Targeted Adverse Event
Time frame: Treatment initiation to Week 48
Percentage of Participants With Serum Total Testosterone < 50 ng/dL at Each Received Dose of Oral 17-β Estradiol
Time frame: Study entry to week 48
Percentage of Participants With Virologic Suppression of HIV
Time frame: Study entry and weeks 12, 24,36 and 48
Absolute Changes in Overall Transgender Congruence Score (TCS)
Time frame: Study entry to weeks 24, and 48
Area Under the Curve Over 8 Hours (AUC 0-8h) of 17-β Estradiol
Time frame: Study entry and Weeks 24, and 48
Percent Change in Weight
Time frame: Study entry to weeks 4,12, 24, 36, and 48
Percent Change in Body Mass Index (BMI)
Time frame: Study entry and weeks 4, 12, 24, 36, and 48
Absolute Change in Minimum Waist Circumference
Time frame: Study entry and weeks 4,12, 24, 36, and 48
Absolute Change in Maximum Hip Circumference
Time frame: Study entry and weeks 4, 12, 24, 36, and 48
Absolute Change in Waist-hip Ratio (WHR) Measured
Time frame: Study entry and weeks 4,12, 24, 36, and 48
Absolute Changes in Fasting High-density Lipoprotein Cholesterol (HDL)
Time frame: Study entry and weeks 12, 24, and 48
Absolute Changes in Fasting Blood Glucose (FBG)
Time frame: Study entry to weeks 4,12, 24, 36, and 48
Absolute Changes in Insulin Sensitivity
Time frame: Study entry and weeks 12, 24, 36, and 48
Absolute Changes in Fasting Triglycerides (TRG)
Time frame: Study entry to weeks 12, 24, and 48
Absolute Changes in Fasting Total Cholesterol (CHOL)
Time frame: Study entry to weeks 12, 24, and 48
Absolute Changes in Fasting Direct Low-density Lipoprotein Cholesterol (LDL)
Time frame: Study entry to weeks 12, 24, and 48
Absolute Change in Weight
Time frame: Study entry to weeks 4,12, 24, 36, and 48
Absolute Change in Body Mass Index (BMI)
Time frame: Study entry to weeks 4, 12, 24, 36, and 48
Percent Change in Minimum Waist Circumference
Time frame: Study entry and weeks 4,12, 24, 36, and 48
Percent Change in Maximum Hip Circumference
Time frame: Study entry and weeks 4, 12, 24, 36, and 48
Percent Change in Waist-hip Ratio (WHR) Measured
Time frame: Study entry and weeks 4,12, 24, 36, and 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1 - July 20, 2017Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification.
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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.
Jordan E. Lake, MD, MSc study chair
Houston AIDS Research Team CRS
Kimberly K. Scarsi, PharmD, MS, FCCP study chair
University of Nebraska
Jorge A. Gallardo-Cartagena, MD study chair
Barranco CRS
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estradiol in people with HIV I Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in 4 countries.
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 15 inclusion and 15 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: stopped early, as of the sponsor's last update on 8 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 18 sites in United States, Thailand, Mexico, Peru. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 8 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?
Geometric Ratio of Antiretroviral Treatment (ART) Analytes Bictegravir (BIC), Dolutegravir (DTG), and Darunavir (DRV) Trough Concentrations (Ctrough) in Plasma at Each Received Dose of Oral 17-β Estradiol (time frame: Study Entry and Weeks 4, 12, 24, 36, and 48). The study lists 3 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 8 Apr 2026.