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TerminatedNCT06005610GETITRIgHTUpdated Apr 8, 2026Results posted

Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy

A Phase 2 interventional study of Estradiol in HIV I Infection, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 18 sites in 4 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-08.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment

Why this study was terminated
Trial terminated by Sponsor.
Phase
Phase 2
Study type
Interventional
Enrollment
93
Allocation
Non-randomized
Ages
18 Years and older
Sex
Male
01

Study 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). 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.

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.

02

Conditions studied

  • HIV I Infection

Keywords

  • HIV
  • Transgender women
  • Estradiol
  • ART
  • Drug interactions
03

In context

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.

Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  1. Documentation of HIV-1 status.
  2. 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.
  3. 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.
  4. Desire to initiate or restart FHT, regardless of orchiectomy status.
  5. HIV-1 RNA \<200 copies/mL at screening.
  6. 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.

  7. 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
  8. Serum estradiol level \<75 pg/mL within 60 days prior to study entry.
  9. 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.
  10. Ability and willingness of participant to provide informed consent and ability and willingness of participant to undergo study procedures.

Exclusion criteria

Exclusion Criteria:

  1. 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.
  2. Known liver impairment or disease.
  3. History of chronic hepatitis B virus (HBV) infection or active HBV infection.
  4. History of current active hepatitis C virus (HCV) infection.
  5. Prohibited medication use (including drugs with known or expected DDIs with FHT or ART) at time of study entry.
  6. 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.
  7. 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.
  8. Personal history of breast cancer. or known personal history of breast cancer (BRCA) gene.
  9. Known or a history of testicular cancer.
  10. Known or a history of gall bladder disease.
  11. Known or suspected pituitary adenoma.
  12. Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  13. 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).
  14. 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.
  15. Presence of any other medical condition that would preclude FHT administration for safety reasons, in the opinion of the site investigator.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
93 participants (actual)

Study arms

  • Experimental
    Group 1: Estradiol among BIC-treated

    Participants taking bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC) who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg.

    Drug: Estradiol

  • Experimental
    Group 2: Estradiol among DTG-treated

    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.

    Drug: Estradiol

  • Experimental
    Group 3: Estradiol among DRV/c-treated

    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.

    Drug: Estradiol

Interventions

  • DrugEstradiol

    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.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48

  2. 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.

    Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48

  3. 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.

    Time frame: Study Entry and Weeks 4, 12, 24, 36, and 48

Secondary outcomes

  1. 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.

    Time frame: Study Entry and Weeks 4, 12, 24, 36 and 48

  2. 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.

    Time frame: Study Entry and Weeks 4, 12, 24, 36 and 48

  3. 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.

    Time frame: Treatment initiation to Week 48

  4. 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).

    Time frame: Treatment initiation to Week 48

  5. 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.

    Time frame: Study entry to week 48

  6. Percentage of Participants With Virologic Suppression of HIV

    Virologic suppression of HIV is defined as plasma HIV-1 viral load \<50 copies/mL.

    Time frame: Study entry and weeks 12, 24,36 and 48

  7. 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.

    Time frame: Study entry to weeks 24, and 48

  8. 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.

    Time frame: Study entry and Weeks 24, and 48

  9. 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.

    Time frame: Study entry to weeks 4,12, 24, 36, and 48

  10. 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.

    Time frame: Study entry and weeks 4, 12, 24, 36, and 48

  11. 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.

    Time frame: Study entry and weeks 4,12, 24, 36, and 48

  12. 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.

    Time frame: Study entry and weeks 4, 12, 24, 36, and 48

  13. 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.

    Time frame: Study entry and weeks 4,12, 24, 36, and 48

  14. 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.

    Time frame: Study entry and weeks 12, 24, and 48

  15. 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.

    Time frame: Study entry to weeks 4,12, 24, 36, and 48

  16. 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.

    Time frame: Study entry and weeks 12, 24, 36, and 48

  17. 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.

    Time frame: Study entry to weeks 12, 24, and 48

  18. 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.

    Time frame: Study entry to weeks 12, 24, and 48

  19. 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.

    Time frame: Study entry to weeks 12, 24, and 48

  20. Absolute Change in Weight

    Calculated as weight in kilograms (kg) at follow-up time minus weight at study entry.

    Time frame: Study entry to weeks 4,12, 24, 36, and 48

  21. Absolute Change in Body Mass Index (BMI)

    Calculated as BMI (in kg/m\^2) at follow-up time minus BMI at study entry.

    Time frame: Study entry to weeks 4, 12, 24, 36, and 48

  22. 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.

    Time frame: Study entry and weeks 4,12, 24, 36, and 48

  23. 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.

    Time frame: Study entry and weeks 4, 12, 24, 36, and 48

  24. 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.

    Time frame: Study entry and weeks 4,12, 24, 36, and 48

07

Results

Posted Apr 8, 2026
Limitations and caveats
Trial was terminated by the sponsor before some participants completed follow-up. Additionally, funding from sponsor unavailable to conduct planned batched testing of stored samples required to generate data for primary and a number of secondary outcomes.

Participant flow

Participants enrolled from 18 sites. Sites were located in the United States and internationally (Mexico, Peru, and Thailand). The first participant enrolled in January 2024, and the last participant enrolled in April 2025.

Participant flow — Overall Study
MilestoneGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Started354018
Completed28164
Not completed72414
Withdrew: Study terminated by sponsor11312
Withdrew: Withdrawal by subject270
Withdrew: Lost to follow-up320
Withdrew: Protocol violation111
Withdrew: Need for prohibited medication001
Withdrew: Undergo gender-affirming surgery010

Outcome measures

PrimaryGeometric 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.

Time frame:
Study Entry and Weeks 4, 12, 24, 36, and 48

No measurements were reported for this outcome.

PrimaryPercentage 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.

Time frame:
Study Entry and Weeks 4, 12, 24, 36, and 48

No measurements were reported for this outcome.

PrimaryTrough 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.

Time frame:
Study Entry and Weeks 4, 12, 24, 36, and 48

No measurements were reported for this outcome.

SecondaryGeometric 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.

Time frame:
Study Entry and Weeks 4, 12, 24, 36 and 48

No measurements were reported for this outcome.

SecondaryPercentage 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.

Time frame:
Study Entry and Weeks 4, 12, 24, 36 and 48

No measurements were reported for this outcome.

SecondaryPercentage 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.

Time frame:
Treatment initiation to Week 48
Reported as:
Number · percentage of participants
Percentage of Participants With an Occurrence of Any Reportable Adverse Event Related to 17-β Estradiol
percentage of participantsGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Percentage of Participants With an Occurrence of Any Reportable Adverse Event Related to 17-β Estradiol32522
SecondaryPercentage 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).

Time frame:
Treatment initiation to Week 48
Reported as:
Number · percentage of participants
Percentage of Participants With an Occurrence of Any Targeted Adverse Event
percentage of participantsGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Percentage of Participants With an Occurrence of Any Targeted Adverse Event636
SecondaryPercentage 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.

Time frame:
Study entry to week 48
Reported as:
Number · percentage of participants
Percentage of Participants With Serum Total Testosterone < 50 ng/dL at Each Received Dose of Oral 17-β Estradiol
percentage of participantsGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
2 mg 17-β estradiol11617
4 mg 17-β estradiol161120
6 mg 17-β estradiol20538
8 mg 17-β estradiol182575
10 mg 17-β estradiol818—
SecondaryPercentage of Participants With Virologic Suppression of HIV

Virologic suppression of HIV is defined as plasma HIV-1 viral load \<50 copies/mL.

Time frame:
Study entry and weeks 12, 24,36 and 48
Reported as:
Number · Percentage of participants
Percentage of Participants With Virologic Suppression of HIV
Percentage of participantsGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 12: Virologic Suppression9410088
Week 24: Virologic Suppression8810092
Week 36: Virologic Suppression899667
Week 48: Virologic Suppression93100100
SecondaryAbsolute 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.

Time frame:
Study entry to weeks 24, and 48
Reported as:
Median · score on a scale
Absolute Changes in Overall Transgender Congruence Score (TCS)
score on a scaleGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 24: Change in TCS from entry0.08 (-0.08 to 0.67)0.33 (-0.17 to 0.67)0.00 (0.00 to 0.33)
Week 48: Change in TCS from entry0.00 (-0.25 to 0.50)0.42 (0.17 to 0.83)0.25 (-0.13 to 0.79)
SecondaryArea 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.

Time frame:
Study entry and Weeks 24, and 48

No measurements were reported for this outcome.

SecondaryPercent 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.

Time frame:
Study entry to weeks 4,12, 24, 36, and 48
Reported as:
Median · percent change
Percent Change in Weight
percent changeGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in weight0.0 (-1.8 to 1.2)0.4 (-0.3 to 1.6)0.2 (-1.2 to 1.2)
Week 12: Change in weight from entry-0.5 (-3.0 to 1.9)0.1 (-1.6 to 2.2)-0.4 (-1.8 to 1.5)
Week 24: Change in weight from entry-0.6 (-3.4 to 3.2)0.6 (-1.0 to 2.7)0.2 (-1.8 to 3.7)
Week 36: Change in weight from entry-0.3 (-4.8 to 4.4)-0.6 (-2.3 to 3.3)0.7 (-0.4 to 5.1)
Week 48: Change in weight from entry0.0 (-3.4 to 4.5)1.5 (-0.6 to 3.8)1.6 (-2.3 to 2.9)
SecondaryPercent 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.

Time frame:
Study entry and weeks 4, 12, 24, 36, and 48
Reported as:
Median · percent change
Percent Change in Body Mass Index (BMI)
percent changeGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in BMI from entry0.0 (-1.8 to 1.2)0.4 (-0.3 to 1.6)0.2 (-1.2 to 1.2)
Week 12: Change in BMI from entry-0.5 (-3.0 to 1.9)0.0 (-1.6 to 1.8)-0.4 (-1.8 to 1.5)
Week 24: Change in BMI from entry-0.6 (-3.4 to 3.2)0.6 (-1.2 to 2.6)0.2 (-1.8 to 3.7)
Week 36: Change in BMI from entry-0.3 (-4.8 to 4.4)-0.7 (-2.3 to 3.3)0.7 (-0.4 to 5.1)
Week 48: Change in BMI from entry0.0 (-3.4 to 4.5)1.2 (-1.6 to 4.0)1.6 (-2.3 to 2.9)
SecondaryAbsolute 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.

Time frame:
Study entry and weeks 4,12, 24, 36, and 48
Reported as:
Median · centimeters
Absolute Change in Minimum Waist Circumference
centimetersGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in waist circumference from entry-1.0 (-3.0 to 0.3)0.6 (-2.0 to 1.0)0.0 (-1.0 to 1.0)
Week 12: Change in waist circumference from entry-1.0 (-2.0 to 0.4)0.4 (-1.1 to 2.4)0.2 (-2.0 to 1.2)
Week 24: Change in waist circumference from entry-0.1 (-2.2 to 2.4)-0.3 (-1.0 to 2.3)2.4 (-0.7 to 4.7)
Week 36: Change in waist circumference from entry0.0 (-2.0 to 2.0)-1.4 (-2.9 to 1.6)3.0 (-1.8 to 5.5)
Week 48: Change in waist circumference from entry-0.2 (-3.7 to 2.9)0.0 (-3.0 to 2.4)3.6 (-0.1 to 5.4)
SecondaryAbsolute 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.

Time frame:
Study entry and weeks 4, 12, 24, 36, and 48
Reported as:
Median · centimeters
Absolute Change in Maximum Hip Circumference
centimetersGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in hip circumference from entry-0.4 (-1.5 to 1.6)0.6 (-0.3 to 1.4)0.2 (0.0 to 1.0)
Week 12: Change in hip circumference from entry0.8 (-2.6 to 2.0)0.5 (-0.4 to 2.5)1.6 (0.0 to 3.0)
Week 24: Change in hip circumference from entry0.7 (-1.8 to 2.5)0.9 (-1.0 to 3.3)1.8 (-0.1 to 3.6)
Week 36: Change in hip circumference from entry1.1 (0.0 to 2.9)1.1 (-1.0 to 3.8)0.0 (-2.1 to 2.1)
Week 48: Change in hip circumference from entry0.8 (-4.0 to 3.7)3.1 (0.6 to 3.9)0.8 (-3.8 to 5.1)
SecondaryAbsolute Change in Waist-hip Ratio (WHR) Measured

Calculated as waist-hip ratio (WHR) at later time point minus waist-hip ratio at study entry.

Time frame:
Study entry and weeks 4,12, 24, 36, and 48
Reported as:
Median · ratio
Absolute Change in Waist-hip Ratio (WHR) Measured
ratioGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in WHR from entry0.00 (-0.03 to 0.02)0.00 (-0.03 to 0.01)0.00 (-0.02 to 0.01)
Week 12: Change in WHR from entry-0.01 (-0.02 to 0.02)0.00 (-0.02 to 0.01)-0.01 (-0.04 to 0.01)
Week 24: Change in WHR from entry-0.01 (-0.02 to 0.01)-0.01 (-0.03 to 0.01)0.00 (-0.01 to 0.01)
Week 36: Change in WHR from entry-0.02 (-0.04 to 0.00)-0.01 (-0.06 to 0.01)0.00 (-0.01 to 0.03)
Week 48: Change in WHR from entry0.00 (-0.02 to 0.01)-0.03 (-0.04 to 0.03)0.01 (-0.01 to 0.05)
SecondaryAbsolute 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.

Time frame:
Study entry and weeks 12, 24, and 48
Reported as:
Median · mg/dL
Absolute Changes in Fasting High-density Lipoprotein Cholesterol (HDL)
mg/dLGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 12: Change in HDL from entry1.0 (-3.0 to 7.0)2.0 (-1.7 to 8.4)-3.3 (-6.5 to 2.6)
Week 24: Change in HDL from entry5.5 (-2.0 to 8.0)2.5 (-1.2 to 8.4)4.0 (2.3 to 10.5)
Week 48: Change in HDL from entry6.5 (0.0 to 12.0)5.0 (1.0 to 10.6)6.5 (4.5 to 9.5)
SecondaryAbsolute 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.

Time frame:
Study entry to weeks 4,12, 24, 36, and 48
Reported as:
Median · mg/dL
Absolute Changes in Fasting Blood Glucose (FBG)
mg/dLGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in FBG from entry2.0 (-3.0 to 10.0)2.0 (-1.5 to 5.9)0.0 (-6.0 to 5.0)
Week 12: Change in FBG from entry-2.0 (-7.0 to 6.0)3.5 (0.0 to 7.0)-2.5 (-8.5 to 4.0)
Week 24: Change in FBG from entry1.0 (-7.0 to 5.0)-0.7 (-4.6 to 3.5)-3.0 (-8.0 to 5.7)
Week 36: Change in FBG from entry-1.5 (-8.0 to 4.5)2.0 (-3.0 to 7.0)-4.0 (-6.0 to 20.0)
Week 48: Change in FBG from entry0.5 (-7.0 to 5.0)7.0 (-1.0 to 8.0)7.0 (-5.0 to 24.0)
SecondaryAbsolute 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.

Time frame:
Study entry and weeks 12, 24, 36, and 48

No measurements were reported for this outcome.

SecondaryAbsolute 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.

Time frame:
Study entry to weeks 12, 24, and 48
Reported as:
Median · mg/dL
Absolute Changes in Fasting Triglycerides (TRG)
mg/dLGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 12: Change in TRG from entry8.5 (-12.0 to 29.0)26.5 (-1.0 to 55.0)28.0 (1.5 to 66.5)
Week 24: Change in TRG from entry9.5 (-28.0 to 45.0)24.5 (4.5 to 43.1)34.0 (-13.0 to 66.0)
Week 48: Change in TRG from entry-0.5 (-13.0 to 31.0)32.0 (12.0 to 49.0)-60.5 (-122.0 to 21.0)
SecondaryAbsolute 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.

Time frame:
Study entry to weeks 12, 24, and 48
Reported as:
Median · mg/dL
Absolute Changes in Fasting Total Cholesterol (CHOL)
mg/dLGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 12: Change in CHOL from entry-9.5 (-20.0 to 10.0)4.4 (-11.7 to 15.5)-9.0 (-23.5 to 7.5)
Week 24: Change in CHOL from entry-6.0 (-23.0 to 13.0)-5.5 (-20.5 to 12.5)5.0 (-8.0 to 23.0)
Week 48: Change in CHOL from entry1.0 (-21.0 to 16.0)5.0 (-1.0 to 23.0)0.5 (-45.5 to 14.0)
SecondaryAbsolute 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.

Time frame:
Study entry to weeks 12, 24, and 48
Reported as:
Median · mg/dL
Absolute Changes in Fasting Direct Low-density Lipoprotein Cholesterol (LDL)
mg/dLGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 12: Change in LDL from entry-12.0 (-30.0 to -1.0)-9.0 (-27.0 to 9.1)-12.5 (-23.2 to 1.0)
Week 24: Change in LDL from entry-14.0 (-19.0 to -2.0)-12.9 (-29.0 to -6.0)4.0 (-25.0 to 20.0)
Week 48: Change in LDL from entry-5.0 (-23.0 to 9.0)-6.2 (-17.5 to 9.9)-12.0 (-52.0 to 28.0)
SecondaryAbsolute Change in Weight

Calculated as weight in kilograms (kg) at follow-up time minus weight at study entry.

Time frame:
Study entry to weeks 4,12, 24, 36, and 48
Reported as:
Median · change in kilograms (kg)
Absolute Change in Weight
change in kilograms (kg)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in weight from entry0.0 (-1.5 to 0.8)0.3 (-0.2 to 1.2)0.1 (-1.0 to 1.0)
Week 12: Change in weight from entry-0.5 (-2.6 to 1.6)0.1 (-1.1 to 1.3)-0.4 (-1.5 to 1.1)
Week 24: Change in weight from entry-0.6 (-3.0 to 2.6)0.4 (-0.8 to 2.5)0.1 (-1.4 to 2.3)
Week 36: Change in weight from entry-0.3 (-3.2 to 4.8)-0.4 (-1.6 to 2.4)0.6 (-0.5 to 3.6)
Week 48: Change in weight from entry0.0 (-2.9 to 3.4)0.9 (-0.4 to 2.7)1.3 (-2.8 to 2.3)
SecondaryAbsolute Change in Body Mass Index (BMI)

Calculated as BMI (in kg/m\^2) at follow-up time minus BMI at study entry.

Time frame:
Study entry to weeks 4, 12, 24, 36, and 48
Reported as:
Median · change in kg/m^2
Absolute Change in Body Mass Index (BMI)
change in kg/m^2Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in BMI from entry0.0 (-0.5 to 0.3)0.1 (-0.1 to 0.4)0.1 (-0.3 to 0.4)
Week 12: Change in BMI from entry-0.2 (-0.9 to 0.5)0.0 (-0.4 to 0.4)-0.1 (-0.6 to 0.4)
Week 24: Change in BMI from entry-0.2 (-1.1 to 0.9)0.1 (-0.3 to 0.9)0.0 (-0.5 to 0.9)
Week 36: Change in BMI from entry-0.1 (-1.2 to 1.5)-0.1 (-0.5 to 0.7)0.2 (-0.1 to 1.2)
Week 48: Change in BMI from entry0.0 (-1.0 to 1.1)0.3 (-0.3 to 0.9)0.5 (-0.8 to 0.8)
SecondaryPercent 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.

Time frame:
Study entry and weeks 4,12, 24, 36, and 48
Reported as:
Median · percent change
Percent Change in Minimum Waist Circumference
percent changeGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in waist circumference from entry-1.2 (-3.0 to 0.3)0.7 (-2.7 to 1.3)0.0 (-1.4 to 1.1)
Week 12: Change in waist circumference from entry-1.1 (-2.2 to 0.4)0.4 (-1.4 to 2.6)0.1 (-2.4 to 1.5)
Week 24: Change in waist circumference from entry-0.2 (-2.6 to 2.2)-0.4 (-1.4 to 2.5)2.4 (-0.4 to 5.4)
Week 36: Change in waist circumference from entry0.0 (-2.4 to 1.5)-1.8 (-3.6 to 1.8)3.0 (-1.1 to 6.1)
Week 48: Change in waist circumference from entry-0.2 (-3.8 to 3.1)0.0 (-3.7 to 2.0)3.4 (-0.4 to 5.6)
SecondaryPercent 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.

Time frame:
Study entry and weeks 4, 12, 24, 36, and 48
Reported as:
Median · percent change
Percent Change in Maximum Hip Circumference
percent changeGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in hip circumference from entry-0.3 (-1.6 to 1.5)0.6 (-0.3 to 1.6)0.2 (0.0 to 1.0)
Week 12: Change in hip circumference from entry0.8 (-2.6 to 1.6)0.5 (-0.4 to 2.6)1.4 (0.0 to 3.0)
Week 24: Change in hip circumference from entry0.6 (-1.6 to 2.5)1.0 (-1.1 to 3.4)1.6 (-0.2 to 4.1)
Week 36: Change in hip circumference from entry1.0 (0.0 to 2.8)1.0 (-0.9 to 4.0)0.0 (-1.2 to 2.1)
Week 48: Change in hip circumference from entry0.9 (-3.2 to 4.2)3.3 (0.7 to 4.0)0.6 (-3.3 to 5.0)
SecondaryPercent 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.

Time frame:
Study entry and weeks 4,12, 24, 36, and 48
Reported as:
Median · percent change
Percent Change in Waist-hip Ratio (WHR) Measured
percent changeGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Week 4: Change in WHR from entry-0.5 (-3.2 to 1.7)-0.4 (-3.1 to 1.1)0.0 (-2.2 to 0.9)
Week 12: Change in WHR from entry-1.4 (-2.6 to 2.2)-0.2 (-2.4 to 1.7)-1.6 (-4.7 to 1.1)
Week 24: Change in WHR from entry-0.9 (-2.9 to 1.5)-1.3 (-3.4 to 0.7)0.1 (-1.7 to 1.2)
Week 36: Change in WHR from entry-2.0 (-4.0 to 0.0)-1.7 (-6.7 to 1.1)0.1 (-0.9 to 3.4)
Week 48: Change in WHR from entry-0.5 (-2.4 to 1.5)-3.9 (-5.1 to 3.7)0.8 (-1.4 to 7.5)

Adverse events

Collected over From treatment initiation to study completion at Week 48 or premature study discontinuation. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Group 1: Estradiol Among BIC-treated0/35 (0%)2/35 (5.7%)17/35 (48.6%)
Group 2: Estradiol Among DTG-treated0/40 (0%)0/40 (0%)28/40 (70%)
Group 3: Estradiol Among DRV/C-treated0/18 (0%)1/18 (5.6%)10/18 (55.6%)
Most frequent serious events
Most frequent serious events
EventGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Chest painGeneral disorders0/350/401/18
Pulmonary sepsisInfections and infestations1/350/400/18
HyponatraemiaMetabolism and nutrition disorders1/350/400/18
DizzinessNervous system disorders1/350/400/18
Most frequent other events
Showing 10 of 31
Most frequent other events
EventGroup 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treated
Glomerular filtration rate decreasedInvestigations13/3515/403/18
Blood triglycerides increasedInvestigations2/355/404/18
Blood cholesterol increasedInvestigations1/356/402/18
HypertriglyceridaemiaMetabolism and nutrition disorders0/355/400/18
Creatinine renal clearance decreasedInvestigations4/350/400/18
Low density lipoprotein increasedInvestigations1/354/401/18
HypercholesterolaemiaMetabolism and nutrition disorders0/354/400/18
HyperglycaemiaMetabolism and nutrition disorders1/353/400/18
Blood glucose increasedInvestigations2/350/400/18
VomitingGastrointestinal disorders0/350/401/18

Baseline characteristics

Participants who initiated 17-beta estradiol study treatment.

Age, Continuous
Age, Continuous(years)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Median43 (33 to 50)34 (30 to 40)42 (32 to 54)38 (32 to 49)
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Male sex and currently identifies as female gender35401893
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Hispanic or Latino1115733
Not Hispanic or Latino23251159
Unknown or Not Reported1001
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Black192829
Asian123428
White111315
Multiple1001
Other014317
Unknown or not reported3003
Region of Enrollment
Region of Enrollment(Participants)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
United States3531149
Mexico0033
Peru014014
Thailand023427
Percentage of participants with virologic suppression of HIV (plasma HIV-1 RNA < 50 copies/mL)
Percentage of participants with virologic suppression of HIV (plasma HIV-1 RNA < 50 copies/mL)(percentage of participants)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Number94959494
Transgender Congruence Score (TCS)
Transgender Congruence Score (TCS)(score)Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Median4.2 (3.7 to 4.8)4.2 (4.0 to 4.6)4.0 (3.5 to 4.9)4.2 (3.7 to 4.7)
Fasting Blood Glucose
Fasting Blood Glucose(milligrams per deciliter (mg/dL))Group 1: Estradiol Among BIC-treatedGroup 2: Estradiol Among DTG-treatedGroup 3: Estradiol Among DRV/C-treatedTotal
Median93.5 (86.0 to 96.0)90.0 (85.0 to 99.0)87.5 (75.0 to 101.0)90.7 (85.0 to 96.0)

9 further baseline measures are reported on the registry.

08

Study locations

18 sites
  • UCSD Antiviral Research Center CRS (701)
    San Diego, California 92103, United States
  • University of California, San Francisco HIV/AIDS CRS (801)
    San Francisco, California 94110, United States
  • University of Colorado Hospital CRS (6101)
    Aurora, Colorado 80045, United States
  • Whitman-Walker Institute, Inc. CRS (31791)
    Washington D.C., District of Columbia 20005, United States
  • The Ponce de Leon Center CRS (5802)
    Atlanta, Georgia 30308, United States
  • Johns Hopkins University CRS (201)
    Baltimore, Maryland 21205, United States
  • Washington University Therapeutics (WT) CRS (2101)
    St Louis, Missouri 63110-1010, United States
  • New Jersey Medical School Clinical Research Center CRS (31786)
    Newark, New Jersey 07103, United States
  • Weill Cornell Uptown CRS (site 7803)
    New York, New York 10065, United States
  • Chapel Hill CRS (3201)
    Chapel Hill, North Carolina 27599-7215, United States
  • Greensboro CRS (3203)
    Greensboro, North Carolina 27401, United States
  • Case CRS (2501)
    Cleveland, Ohio 44106, United States
  • Vanderbilt Therapeutics CRS (3652)
    Nashville, Tennessee 37204, United States
  • Houston AIDS Research Team CRS (31473)
    Houston, Texas 77030, United States
  • Nutrición-Mexico CRS (32078)
    Mexico City, Tlalpan 14080, Mexico
  • Barranco CRS (11301)
    Lima, 4, Peru
  • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (31802)
    Bangkok, Patumwan 10330, Thailand
  • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (31784)
    Chiang Mai, 50200, Thailand
09

References and documents

Study documents

  • Protocol and informed consent form · Jun 30, 2023
  • Study protocol · Jan 17, 2024
  • Study protocol · Jan 22, 2024
  • Study protocol · Mar 21, 2024
  • Statistical analysis plan · Jun 30, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Individual participant data that underlie results in the publication, after deidentification.

Supporting information: Study protocol, Sap

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT06005610
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Aug 22, 2023
Start date
Jan 4, 2024
Primary completion
Aug 21, 2025
Completion
Aug 21, 2025
Results posted
Apr 8, 2026
Last update
Apr 8, 2026

Study contacts

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

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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