Estradiol Therapy In Transgender Women to Research Intera... | NCT06005610

NCT06005610

ID	Type	Description	Link
38806	Other Identifier	DAIDS-ES ID

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

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 Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: Estradiol

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Estradiol	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	Study Entry and Weeks 4, 12, 24, 36, and 48

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
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.

Exclusion Criteria:

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.
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.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Jordan E. Lake, MD, MSc	Houston AIDS Research Team CRS	Study Chair
Kimberly K. Scarsi, PharmD, MS, FCCP	University of Nebraska	Study Chair
Jorge A. Gallardo-Cartagena, MD	Barranco CRS	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
UCSD Antiviral Research Center CRS (701)		San Diego	California	92103	United States
University of California, San Francisco HIV/AIDS CRS (801)

References Module

Label	URL
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, 2017	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Group 2: Estradiol Among DTG-treated

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_ICF	Yes	No	Yes	Study Protocol and Informed Consent Form: Version 2.0	Jun 30, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Participants who initiated 17-beta estradiol study treatment.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG00140 ParticipantsBG00218 ParticipantsBG003

Sex/Gender, Customized

Sex at birth and current gender identity

Count of Participants

Participants

Title	Denominators	Categories
Male sex and currently identifies as female gender	ParticipantsBG00035 ParticipantsBG00140 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG00140 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
Black	ParticipantsBG00035 ParticipantsBG00140 ParticipantsBG002

Region of Enrollment

Number

Participants

Title	Denominators	Categories
United States	ParticipantsBG00035 ParticipantsBG00140 ParticipantsBG002

Percentage of participants with virologic suppression of HIV (plasma HIV-1 RNA < 50 copies/mL)

Missing plasma HIV-RNA results from entry visit excluded.

Number

percentage of participants

Title	Denominators	Categories
	ParticipantsBG00033 ParticipantsBG00139 ParticipantsBG002

Transgender Congruence Score (TCS)

Score was calculated from participant response to 12-question where each item is rated 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.

Questionnaire must be completed with all 12 questions answered. Incomplete or missing questionnaires excluded.

Median

Inter-Quartile Range

score

Title	Denominators	Categories
	ParticipantsBG00034 ParticipantsBG001

Fasting Blood Glucose

FBG results required valid results from glucose test from a fasting blood sample drawn prior to treatment initiation. Missing results excluded.

Median

Inter-Quartile Range

milligrams per deciliter (mg/dL)

Title	Denominators	Categories
	ParticipantsBG00034 ParticipantsBG00139 ParticipantsBG002

Weight

Total body weight

Missing values excluded

Median

Inter-Quartile Range

kilograms

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG00139 ParticipantsBG002

Body Mass Index

Calculated as from weight measured at entry and height measured at any time.

If participant missing either entry weight or height, BMI value is missing.

Median

Inter-Quartile Range

kilograms per meter squared

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG00138 ParticipantsBG002

Minimum Waist circumference

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.

Missing values excluded.

Median

Inter-Quartile Range

centimeters

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG001

Maximum hip circumference

Measurements taken over undergarments or non-bulky clothing. Measured while facing the participant's right side by placing the tape around the hips so that it passed over the greatest protrusion of the gluteus muscles, and with tape level and parallel to floor. Sufficient tension applied to minimize any effect of clothing. The participant was standing erect but relaxed, and asked not to hold in stomach. Measurements taken in triplicate to nearest millimeter and average reported (excluding any value more than 10% different from others).

Missing values excluded

Median

Inter-Quartile Range

centimeters

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG001

Waist-Hip Ratio

Calculated from minimum waist circumference and maximum hip circumference as described in those measures.

Missing values excluded.

Median

Inter-Quartile Range

ratio

Title	Denominators	Categories
	ParticipantsBG00035 ParticipantsBG00139 ParticipantsBG002

Fasting Direct Low-Density Lipoprotein (LDL)

Measurements in non-fasting state or calculated (versus directly measured) were excluded.

Median

Inter-Quartile Range

milligrams per deciliter

Title	Denominators	Categories
	ParticipantsBG00027 ParticipantsBG00137 ParticipantsBG002

Fasting Total Cholesterol

Measurements in non-fasting state excluded.

Median

Inter-Quartile Range

milligrams per deciliter

Title	Denominators	Categories
	ParticipantsBG00034 ParticipantsBG00139 ParticipantsBG002

Fasting Triglycerides

Measurements in non-fasting state excluded.

Median

Inter-Quartile Range

milligrams per deciliter

Title	Denominators	Categories
	ParticipantsBG00034 ParticipantsBG00139 ParticipantsBG002

Fasting High-density lipoproteins (HDL)

Measurements in non-fasting state excluded.

Median

Inter-Quartile Range

milligrams per deciliter

Title	Denominators	Categories
	ParticipantsBG00034 ParticipantsBG00139 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study Entry and Weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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. Estradiol: 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.
OG001	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. Estradiol: 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.
OG002	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. Estradiol: 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.

Units	Counts
Participants	OG0000 OG0010 OG0020

Primary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study Entry and Weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Primary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study Entry and Weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	Group 3: Estradiol Among DRV/C-treated

Secondary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study Entry and Weeks 4, 12, 24, 36 and 48

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study Entry and Weeks 4, 12, 24, 36 and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment.

Posted

Number

percentage of participants

Treatment initiation to Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

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).

Participants who initiated 17-beta estradiol study treatment.

Posted

Number

percentage of participants

Treatment initiation to Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants without history of orchiectomy with study entry testosterone level >= 50 ng/dL who initiated 17-β estradiol study treatment. Participants with missing results during follow-up excluded.

Posted

Number

percentage of participants

Study entry to week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Percentage of Participants With Virologic Suppression of HIV

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

Participants who initiated 17-beta estradiol study treatment and who had a measurement of plasma HIV-1 viral load available.

Posted

Number

Percentage of participants

Study entry and weeks 12, 24,36 and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who completed all 12 questions at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

score on a scale

Study entry to weeks 24, and 48

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study entry and Weeks 24, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	Group 3: Estradiol Among DRV/C-treated

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had weight available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

percent change

Study entry to weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had BMI available (i.e. weight measured) at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

percent change

Study entry and weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had waist circumference available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

centimeters

Study entry and weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who had hip circumference available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

centimeters

Study entry and weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who had both waist and hip circumferences measured at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

ratio

Study entry and weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had fasting HDL results available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

mg/dL

Study entry and weeks 12, 24, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who had fasting blood glucose results available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

mg/dL

Study entry to weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

No participants have results as the laboratory testing needed to derive this outcome measure was not performed due to termination of funding. There is no plan to test these samples in the future.

Posted

Study entry and weeks 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had fasting triglycerides results available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

mg/dL

Study entry to weeks 12, 24, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment, and who had fasting total cholesterol results available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

mg/dL

Study entry to weeks 12, 24, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had fasting LDL cholesterol results available at both entry and follow-up timepoint.

Posted

Median

Inter-Quartile Range

mg/dL

Study entry to weeks 12, 24, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Absolute Change in Weight

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

Participants who initiated 17-beta estradiol study treatment who had weight measured at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

change in kilograms (kg)

Study entry to weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Absolute Change in Body Mass Index (BMI)

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

Participants who initiated 17-beta estradiol study treatment and who had BMI available (i.e. weight measured) at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

change in kg/m^2

Study entry to weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-beta estradiol study treatment and who had waist circumference measured at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

percent change

Study entry and weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who had hip circumference measured at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

percent change

Study entry and weeks 4, 12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

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.

Participants who initiated 17-β estradiol study treatment and who had both waist and hip circumferences measured at both entry and follow-up timepoints.

Posted

Median

Inter-Quartile Range

percent change

Study entry and weeks 4,12, 24, 36, and 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	35	2	35	17	35
EG001	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.	40	0	40	28	40
EG002	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.	18	1	18	10	18

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected40 at risk EG0021 affected18 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vision blurred	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected40 at risk EG0021 affected18 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected40 at risk EG0021 affected18 at risk
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Peripheral swelling	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected40 at risk EG0021 affected18 at risk
Blood cholesterol increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0016 affected40 at risk EG0022 affected18 at risk
Blood glucose decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Blood glucose increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk
Blood pressure increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Blood triglycerides increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 affected35 at risk EG0015 affected40 at risk EG0024 affected18 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0004 affected35 at risk EG0010 affected40 at risk EG0020 affected18 at risk
Glomerular filtration rate decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG00013 affected35 at risk EG00115 affected40 at risk EG0023 affected18 at risk
Hepatic enzyme increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Low density lipoprotein increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0014 affected40 at risk EG0021 affected18 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected40 at risk EG0020 affected18 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0014 affected40 at risk EG0020 affected18 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0013 affected40 at risk EG0020 affected18 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0015 affected40 at risk EG0020 affected18 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected40 at risk EG0020 affected18 at risk
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Depression	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Nephropathy	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected40 at risk EG0020 affected18 at risk

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.

Certain Agreements

Point of Contact

Title	Organization	Phone	Extension	Email
ACTG Clinicaltrials.gov Coordinator	ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company	(301) 628-3348		ACTGCT.gov@fstrf.org

First MCP Posted Date

ID	Term
D004958	Estradiol

Ancestor Terms

ID	Term
D004963	Estrenes
D004962	Estranes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045166	Estradiol Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

Units	Counts
Participants	OG00035 OG00140 OG00218

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.

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

Units	Counts
Participants	OG00035 OG00140 OG00218

OG0010.42(0.17 to 0.83)

OG0020.25(-0.13 to 0.79)

OG0010.1(-1.6 to 2.2)

OG002-0.4(-1.8 to 1.5)

OG0010.6(-1.0 to 2.7)

OG0020.2(-1.8 to 3.7)

OG001-0.6(-2.3 to 3.3)

OG0020.7(-0.4 to 5.1)

OG0011.5(-0.6 to 3.8)

OG0021.6(-2.3 to 2.9)

OG0010.0(-1.6 to 1.8)

OG002-0.4(-1.8 to 1.5)

OG0010.6(-1.2 to 2.6)

OG0020.2(-1.8 to 3.7)

OG001-0.7(-2.3 to 3.3)

OG0020.7(-0.4 to 5.1)

OG0011.2(-1.6 to 4.0)

OG0021.6(-2.3 to 2.9)

OG0010.4(-1.1 to 2.4)

OG0020.2(-2.0 to 1.2)

OG001-0.3(-1.0 to 2.3)

OG0022.4(-0.7 to 4.7)

OG001-1.4(-2.9 to 1.6)

OG0023.0(-1.8 to 5.5)

OG0010.0(-3.0 to 2.4)

OG0023.6(-0.1 to 5.4)

OG0010.5(-0.4 to 2.5)

OG0021.6(0.0 to 3.0)

OG0010.9(-1.0 to 3.3)

OG0021.8(-0.1 to 3.6)

OG0011.1(-1.0 to 3.8)

OG0020.0(-2.1 to 2.1)

OG0013.1(0.6 to 3.9)

OG0020.8(-3.8 to 5.1)

OG0010.00(-0.02 to 0.01)

OG002-0.01(-0.04 to 0.01)

OG001-0.01(-0.03 to 0.01)

OG0020.00(-0.01 to 0.01)

OG001-0.01(-0.06 to 0.01)

OG0020.00(-0.01 to 0.03)

OG001-0.03(-0.04 to 0.03)

OG0020.01(-0.01 to 0.05)

OG0012.5(-1.2 to 8.4)

OG0024.0(2.3 to 10.5)

OG0015.0(1.0 to 10.6)

OG0026.5(4.5 to 9.5)

OG0013.5(0.0 to 7.0)

OG002-2.5(-8.5 to 4.0)

OG001-0.7(-4.6 to 3.5)

OG002-3.0(-8.0 to 5.7)

OG0012.0(-3.0 to 7.0)

OG002-4.0(-6.0 to 20.0)

OG0017.0(-1.0 to 8.0)

OG0027.0(-5.0 to 24.0)

OG00124.5(4.5 to 43.1)

OG00234.0(-13.0 to 66.0)

OG00132.0(12.0 to 49.0)

OG002-60.5(-122.0 to 21.0)

OG001-5.5(-20.5 to 12.5)

OG0025.0(-8.0 to 23.0)

OG0015.0(-1.0 to 23.0)

OG0020.5(-45.5 to 14.0)

OG001-12.9(-29.0 to -6.0)

OG0024.0(-25.0 to 20.0)

OG001-6.2(-17.5 to 9.9)

OG002-12.0(-52.0 to 28.0)

OG0010.1(-1.1 to 1.3)

OG002-0.4(-1.5 to 1.1)

OG0010.4(-0.8 to 2.5)

OG0020.1(-1.4 to 2.3)

OG001-0.4(-1.6 to 2.4)

OG0020.6(-0.5 to 3.6)

OG0010.9(-0.4 to 2.7)

OG0021.3(-2.8 to 2.3)

OG0010.0(-0.4 to 0.4)

OG002-0.1(-0.6 to 0.4)

OG0010.1(-0.3 to 0.9)

OG0020.0(-0.5 to 0.9)

OG001-0.1(-0.5 to 0.7)

OG0020.2(-0.1 to 1.2)

OG0010.3(-0.3 to 0.9)

OG0020.5(-0.8 to 0.8)

OG0010.4(-1.4 to 2.6)

OG0020.1(-2.4 to 1.5)

OG001-0.4(-1.4 to 2.5)

OG0022.4(-0.4 to 5.4)

OG001-1.8(-3.6 to 1.8)

OG0023.0(-1.1 to 6.1)

OG0010.0(-3.7 to 2.0)

OG0023.4(-0.4 to 5.6)

OG0010.5(-0.4 to 2.6)

OG0021.4(0.0 to 3.0)

OG0011.0(-1.1 to 3.4)

OG0021.6(-0.2 to 4.1)

OG0011.0(-0.9 to 4.0)

OG0020.0(-1.2 to 2.1)

OG0013.3(0.7 to 4.0)

OG0020.6(-3.3 to 5.0)

OG001-0.2(-2.4 to 1.7)

OG002-1.6(-4.7 to 1.1)

OG001-1.3(-3.4 to 0.7)

OG0020.1(-1.7 to 1.2)

OG001-1.7(-6.7 to 1.1)

OG0020.1(-0.9 to 3.4)

OG001-3.9(-5.1 to 3.7)

OG0020.8(-1.4 to 7.5)