Pre-Exposure Prophylaxis for Transgender Women in the US and South America

HPTN 091: Integrating HIV Prevention, Gender-Affirmative Medical Care, and Peer Health Navigation for Transgender Women in the Americas: A Vanguard Study

A study to assess the feasibility, acceptability, and preliminary impact of a multi-component strategy to improve pre-exposure prophylaxis (PrEP) uptake and adherence that integrates delivery of biomedical HIV prevention co-located with gender-affirming transgender care (hormonal therapy and medical monitoring) and Peer Health Navigation (PHN) using Strengths-Based Case Management (SBCM) professional supervision.

Multi-site, open-label study with each participant randomized 1:1 to Immediate Intervention vs. 6-month Deferred Intervention Arms. Both arms will be provided PrEP and sexually transmitted infection (STI) screening and treatment. Participants in the Immediate Intervention Arm will receive co-located gender-affirming medical care and PHN using SBCM starting at the Enrollment Visit. Participants in the Deferred Intervention Arm will receive linkage to external gender-affirming medical care and case management services during the deferred period and will transition to the study intervention six months following the Enrollment Visit.

Study Overview

• Status: Completed
• Conditions: HIV Prevention
• Intervention / Treatment: Drug: Immediate Intervention Arm; Drug: Deferred Intervention Arm

Detailed Description

entered elsewhere

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro
    • Manguinhos, Rio de Janeiro, Brazil, 221045-900
      • Instituto de Pesquisa Clinicaq Evandro Chagas CRS
• United States
  • California
    • San Francisco, California, United States, 94102
      • Bridge HIV CRS
  • New York
    • New York, New York, United States, 10027
      • Harlem Prevention Center CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Prevention CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• TGW (assigned male at birth, trans-feminine spectrum - as defined in the SSP Manual - by self-report) who meet all of the following criteria are eligible for inclusion in this study.
• Eighteen years or older at the time of screening.
• Willing and able to provide informed consent for the study.
• Interest in PrEP - as defined in the SSP Manual.
• Non-reactive HIV test results at Screening and Enrollment.
• Available to return for all study visits and within site catchment area, as defined per site's Standard Operating Procedures (SOP).

• At risk for sexually acquiring HIV infection based on self-report of at least one of the following:

  1. Any anal or vaginal sex with one or more serodiscordant or HIV-unknown serostatus sexual partners in the previous 3 months, regardless of condom use.
  2. Anal or vaginal sex in exchange for money, food, shelter, or other goods or favors in the previous 3 months.
  3. History of STI(s) in the past 6 months.
• Willing to undergo all required study procedures.

• General good health, as evidenced by the following laboratory values:

  1. Calculated creatinine clearance ≥ 60 mL/minute using the Cockcroft-Gault equation.
  2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the upper limit of normal (ULN.)
  3. HBV surface antigen (HBsAg) negative.

Note: Otherwise eligible participants with laboratory results outside the above-mentioned values, with the exception of those with reactive HIV test, can be re-tested during the screening window. Participants with reactive HIV tests will not be able to rescreen.

Note: Participants who practice receptive vaginal sex cannot be provided Descovy® as it is not approved for this indication.

Exclusion Criteria:

1. Any reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed.
2. Plans to move away from the site area within the next 18 months.
3. Co-enrollment in any other research study that may interfere with this study (as provided by self-report or other available documentation). Exceptions may be made after consultation with the Clinical Management Committee (CMC).
4. Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy).
5. History of deep vein thrombosis, pulmonary embolism, and/or clotting disorder.
6. Active or planned use of medications with significant drug interactions as described in the Package Insert for Truvada® or Descovy®, per clinician's discretion (provided by selfreport or obtained from medical history or medical records). See Section 5.8 for a full list of drug interactions.
7. Any other condition, including but not limited to alcohol or substance abuse and uncontrolled medical condition and/or allergies, that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives would make the patient unsuitable for the study or unable/unwilling to comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate Intervention Arm; PrEP (pre-exposure prophylaxis) provision, STI screening and treatment, GAHT (gender-affirming hormonal therapy), peer-health management using strengths-based management. PrEP provision includes using one daily tablet of Descovy (emtricitabine 200 mg and tenofovir alafenamide 25mg, FTC/TAF) or one daily tablet of Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg, FTC/TDF) in the US, and one daily tablet of Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg, FTC/TDF) in Brazil.	Drug: Immediate Intervention Arm; Truvada, Descovy in the United States; Truvada in Brazil; Other Names: Truvada, Descovy
Experimental: Deferred Intervention Arm; 0-6 months PrEP (pre-exposure prophylaxis) provision and STI screening and treatment. From months 6-18, GAHT (gender-affirming hormonal therapy) and peer-health management using strengths-based management. PrEP provision includes one daily tablet of Descovy (emtricitabine 200 mg and tenofovir alafenamide 25mg, FTC/TAF) or one daily tablet of Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg, FTC/TDF) in the US, and one daily table of Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg, FTC/TDF) in Brazil.	Drug: Deferred Intervention Arm; Truvada, Descovy in the United States; Truvada in Brazil; Other Names: Truvada, Descovy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PrEP Uptake	Time to PrEP initiation is defined as the duration from enrollment to the PrEP start date.	0-18 months
PrEP Adherence	Self-reported adherence to daily PrEP by study visit	0-18 months
Acceptability and Feasibility of Co-located Services	Number of participants accepting co-located GAHT services at baseline and subsequent quarterly study visits.	0-18 months
Participant Retention at Weeks 26, 52 and 78	Participant retention at weeks 26, 52 and 78 by study arm. Retention defined as the number of participants who completed the visit divided by the number of participants who are expected or have completed the visit.	Weeks 26, 52, 78
Acceptability and Feasibility of Peer Health Navigation	The average number of peer health navigator encounters.	0-18 months
Acceptability and Feasibility of Peer Health Navigation	Number of each type of peer health navigation encounter.	0-18 months
Acceptability and Feasibility of Co-located Services	Percentage of participants who report desire for co-located services at the end of the study	0-18 months
PrEP Adherence	The average number of days to first PrEP permanent discontinuation.	0-18 months
PrEP Adherence	The median number of days to first PrEP permanent discontinuation.	0-18 months
PrEP Adherence	Participants with different levels of TFV-DP concentrations in DBS measured at quarterly follow-up visits after PrEP initiation.	0-18 months
PrEP Adherence	Participants with different levels FTC-TP concentrations in DBS measured at quarterly follow-up visits after PrEP initiation.	0-18 months
PrEP Adherence	The proportion of TGW determined to be adherent at the Week 26 visit was compared by study arm. PrEP adherence was defined as having a detectable concentration of PrEP (Truvada or Descovy) in DBS sample.	Week 26
PrEP Persistent	PrEP persistent is defined as the proportion of study visits where a participant demonstrates high adherence to PrEP among those who initiated PrEP at the study clinic. High adherence at a visit is based on drug concentrations in dried blood spots (DBS): Truvada (TDF/FTC): TFV-DP ≥ 900 fmol/punch Descovy (TAF/FTC): TFV-DP ≥ 950 fmol/punch PrEP persistent reflects sustained high PrEP adherence across multiple visits over time, rather than high PrEP adherence at a single point.	0-18 months
PrEP Uptake	Comparison of PrEP uptake between study arms at the end of Week 26. PrEP uptake is defined as whether the participant initiated PrEP at the study clinic..	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examining Changes in Sexual Risk-taking Behavior	Describing condom use with HIV+ people, measured by assessments at enrollment and quarterly through Week 78.	0-18 months
Examining Changes in Sexual Risk-taking Behavior	Describing condom use with HIV unknown people, measured by assessments at enrollment and quarterly through Week 78.	0-18 months
Examining Changes in Sexual Risk-taking Behavior	Frequency of being high on drugs/drunk during sex, measured by assessments at enrollment and quarterly through Week 78.	0-18 months
Examining Changes in Sexual Risk-taking Behavior	Had sex for money/drugs/housing/food/other things, measured by assessments at enrollment and quarterly through Week 78.	0-18 months
Prevalence of STI Infection (GC, CT, Syphilis) at Baseline	To determine baseline prevalence of STIs (Neisseria gonorrhoeae [GC], Chlamydia trachomatis [CT], and Treponema pallidum (syphilis)) by study arm	0 months
Estimate Prevalence of Baseline Laboratory Values.	To obtain baseline laboratory data to evaluate the cohort's suitability for future PrEP intervention studies (e.g., prevalence of renal insufficiency, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, etc.). Logistic regression models will be used for estimating prevalence of baseline conditions.	0 months
Gender-Affirming Hormone Therapy by Visit	Taken hormones for gender identity/transition	0-18 months
Gender-Affirming Hormone Therapy by Visit	Currently taking hormones for gender identity/transition	0-18 months
Gender-Affirming Hormone Therapy by Visit	Where do you currently get your hormones?	0-18 months
Gender-Affirming Hormone Therapy by Visit	Ever had a substance (like silicone or other fillers) injected to fill out face or make figure look more womanly	0-18 months
Gender-Affirming Hormone Therapy by Visit	Ever had breast augmentation/surgery	0-18 months
Gender-Affirming Hormone Therapy by Visit	Ever had vaginoplasty/labiaplasty/SRS/GRS/GCS	0-18 months
Annual Incidence of HIV Infections	The number of incident HIV infections at each time point by arm. Note: The HIV infection reported at Week 26 occurred during an interim visit between Week 26 and Week 39.	0-18 months
Incidence of STI Infection (GC, CT, Syphilis)	To determine annual incidence of STIs (Neisseria gonorrhoeae [GC], Chlamydia trachomatis [CT], and Treponema pallidum (syphilis)) and to examine changes in STI over time by study arm.	0-18 months
Identify Demographic, Behavioral, Socioeconomic, and Psychosocial Factors Related to PrEP Uptake	PrEP uptake is defined as whether the participant initiated PrEP at the study clinic during the study cycle.	0-18 months
Identify Demographic, Behavioral, Socioeconomic, and Psychosocial Factors Associated With PrEP Adherence Across Study Visits.	The number of study visits at which participants were highly adherent to PrEP, among those who initiated PrEP at the study clinic. High adherence at a given visit is determined using drug concentrations in dried blood spots (DBS): Truvada: TFV-DP ≥ 900 fmol/punch Descovy: TFV-DP ≥ 950 fmol/punch Arm-level results are presented as the total number of visits at which participants in each arm were highly adherent to PrEP, reported as the number and percentage of visits.	0-18 months
Identify Demographic, Behavioral, Socioeconomic, and Psychosocial Factors Related to PrEP Persistence	PrEP persistence is defined as the proportion of study visits at which a participant demonstrates high adherence to PrEP among participants who initiated PrEP at the study clinic. High adherence at a given visit is determined using drug concentrations in dried blood spots (DBS): Truvada: TFV-DP ≥ 900 fmol/punch Descovy: TFV-DP ≥ 950 fmol/punch PrEP persistence reflects sustained high adherence across multiple visits over time per participant, rather than overall high adherence at all time points. For each participant, this proportion was converted to a percentage; arm-level results are presented as the mean of participant-level percentages in each arm in the outcome measure data table.	0-18 months
Identify Demographic, Behavioral, Socioeconomic, and Psychosocial Factors Related to Interest in Future HIV Research	An overall composite flag (Yes/No) for interest in future HIV research was created at the end of study using participant responses collected at enrollment, weeks 26, 52, and 78. Those who showed interest in future HIV research (Yes) were reported in the outcome measure data table.	0-18 months

Collaborators and Investigators

• Sponsor: HIV Prevention Trials Network
• Collaborators: Gilead Sciences
• Investigators: Study Chair: Tonia Poteat, PhD, MPH, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2021
• Primary Completion (Actual): August 16, 2024
• Study Completion (Actual): August 16, 2024

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Transgender women; TGW
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Drug Combinations; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; emtricitabine tenofovir alafenamide
• Other Study ID Numbers: HPTN 091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes