Phase 2b, Open Label, Multisite, Randomized Crossover Study of DPP Versus 2PR

February 17, 2026 updated by: HIV Prevention Trials Network

A Multisite, Open-label, Randomized Crossover Study Comparing Adherence to a Single Daily Dual Prevention Pill (DPP) Versus FTC/TDF and Combined Oral Contraception Separate Pill Dosing (2PR), Given for Pre-exposure Prophylaxis and Pregnancy Prevention in Women

To evaluate adherence to a single dual-prevention pill (DPP) compared with a two-pill regimen (2PR) for pre-exposure prophylaxis (PrEP) and pregnancy prevention in women without HIV.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To evaluate adherence to a single DPP consisting of co-formulated Tenofovir Disoproxil Fumarate and Emtricitabine (FTC/TDF) plus combined ethinyl estradiol/levonorgestrel oral contraceptive (COC), compared with a two-pill regimen (2PR) consisting of daily oral FTC/TDF pill and combined COC pill, for pre-exposure prophylaxis PrEP and pregnancy prevention in women without HIV.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Eswatini
      • Mbabane, Eswatini
        • Eswatini Prevention Center CRS
        • Contact:
  • Uganda
      • Kampala, Uganda
        • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
        • Contact:
  • Zimbabwe
      • Harare, Zimbabwe

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 16 through 39 years old (inclusive) at Screening.
  • Adults must be able and willing to provide informed consent. Adolescents (16- and 17-year-olds) will be consented according to applicable local guidelines, by obtaining participant assent and where applicable parental or guardian permission.
  • Able and willing to provide adequate locator information.
  • Able and willing to comply with all study procedures.
  • Must be post-menarche and pre-menopausal and could potentially become pregnant.
  • Sexually active, defined as having had penile-vaginal sex within the 3 months before Screening (per self-report)
  • Negative pregnancy test at Screening and Enrollment.
  • Does not intend to become pregnant within the next 12 months.
  • Willing to use COCs for at least 48 weeks as their method of contraception.
  • HIV negative at Screening and Enrollment.
  • Willing to use oral PrEP for at least 48 weeks.
  • Hepatitis B (HBV) surface antigen (HbsAg) negative per blood test at Screening.
  • Hepatitis C (HCV) negative at Screening.
  • Normal estimated creatinine clearance (eCrCl) ≥ 60 ml/min per blood test at Screening.

Exclusion Criteria:

  • Intolerance, adverse reaction, or laboratory abnormality associated with PrEP use in the past.
  • Unable to become pregnant e.g., had a tubal ligation or hysterectomy or otherwise lacks a uterus, or is currently using another form of contraception.
  • Medically ineligible for combined hormonal contraception and specifically COCs per World Health Organization (WHO) medical eligibility criteria for contraceptive use or similar local medical eligibility guidelines (e.g., Centers for Disease Control and Prevention eligibility criteria).
  • Medically ineligible for PrEP based on WHO and/or local guidelines.
  • Using or planning to use another pregnancy prevention product other than oral contraception (condoms are permitted) during the next 48 weeks.
  • Using or planning to use another HIV prevention product other than condoms during the next 48 weeks.
  • Any other condition the clinician feels would jeopardize the health and wellbeing of the participant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: DPP/2PR/Choice
Daily DPP for 12 weeks followed by daily 2PR for 12 weeks followed by 24 weeks of Choice
Drug: DPP
Daily, single, co-formulated, FTC/TDF + combined ethinyl estradiol/levonorgestrel oral contraceptive pill
Drug: 2PR
Daily, two-pill regimen of oral FTC/TDF and ethinyl estradiol/levonorgestrel oral contraceptive pill
Drug: Free Choice
Choice of either DPP or 2PR
Experimental: 2PR/DPP/Choice
Daily 2PR for 12 weeks followed by daily DPP for 12 weeks followed by 24 weeks of Choice
Drug: DPP
Daily, single, co-formulated, FTC/TDF + combined ethinyl estradiol/levonorgestrel oral contraceptive pill
Drug: 2PR
Daily, two-pill regimen of oral FTC/TDF and ethinyl estradiol/levonorgestrel oral contraceptive pill
Drug: Free Choice
Choice of either DPP or 2PR

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
PrEP adherence to DPP during randomized crossover period 1
Time Frame: Week 12
Intraerythrocytic Tenofovir Diphosphate (TFV-DP) concentrations in dried blood spot (DBS)
Week 12
PrEP adherence to 2PR during randomized crossover period 1
Time Frame: Week 12
Intraerythrocytic TFV-DP concentrations in DBS
Week 12
PrEP adherence to DPP during randomized crossover period 2
Time Frame: Week 24
Intraerythrocytic TFV-DP concentrations in DBS
Week 24
PrEP adherence to 2PR during randomized crossover period 2
Time Frame: Week 24
Intraerythrocytic TFV-DP concentrations in DBS
Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PrEP adherence to DPP during Choice period
Time Frame: Week 48
TFV-DP concentrations in DBS
Week 48
PrEP adherence to 2PR during Choice period
Time Frame: Week 48
TFV-DP concentrations in DBS
Week 48
PrEP adherence to DPP during Choice period
Time Frame: Week 48
Self-reported adherence
Week 48
PrEP adherence to 2PR during Choice period
Time Frame: Week 48
Self-reported adherence
Week 48
Acceptability of DPP during crossover period
Time Frame: Week 24
Answers to acceptability questionnaire based on overall acceptability measure as well as a range of acceptability dimensions (e.g., product size, color, dosing, etc.)
Week 24
Acceptability of 2PR during crossover period
Time Frame: Week 24
Answers to acceptability questionnaire based on overall acceptability measure as well as a range of acceptability dimensions (e.g., product size, color, dosing, etc.)
Week 24
Acceptability of DPP during Choice period
Time Frame: Week 48
Answers to acceptability questionnaire based on overall acceptability measure as well as a range of acceptability dimensions (e.g., product size, color, dosing, etc.)
Week 48
Acceptability of 2PR during Choice period
Time Frame: Week 48
Acceptability of 2PR based on answers to acceptability questionnaire based on overall acceptability measure as well as a range of acceptability dimensions (e.g., product size, color, dosing, etc.)
Week 48
Preference for DPP
Time Frame: Day 0
Preference of DPP at enrollment
Day 0
Preference for DPP
Time Frame: Week 24
Preference of DPP at completion of the crossover phase of the study
Week 24
Preference for 2PR
Time Frame: Day 0
Preference of 2PR at enrollment
Day 0
Preference for 2PR
Time Frame: Week 24
Preference of 2PR at completion of the crossover phase of the study
Week 24
PrEP persistence on DPP during the Choice period
Time Frame: Week 48
Proportion of participants still using their chosen regimen at end of the Choice period
Week 48
PrEP persistence on 2PR during the Choice period
Time Frame: Week 48
Proportion of participants still using their chosen regimen at end of the Choice period
Week 48
Overall tolerability of DPP
Time Frame: Week 48
Tolerability
Week 48
Overall tolerability of 2PR
Time Frame: Week 48
Tolerability
Week 48
Tolerability of DPP during the crossover period
Time Frame: Week 24
Tolerability
Week 24
Tolerability of 2PR during the crossover period
Time Frame: Week 24
Tolerability
Week 24
Tolerability of DPP during the Choice period
Time Frame: Week 48
Tolerability
Week 48
Tolerability of 2PR during the Choice period
Time Frame: Week 48
Tolerability
Week 48
Overall side effects of DPP
Time Frame: Week 48
Grade 2+ Adverse Events (AE)
Week 48
Overall side effects of 2PR
Time Frame: Week 48
Grade 2+ AE
Week 48
Side effects of DPP during the crossover period
Time Frame: Week 24
Grade 2+ AE
Week 24
Side effects of 2PR during the crossover period
Time Frame: Week 24
Grade 2+ AE
Week 24
Side effects of DPP during the Choice period
Time Frame: Week 48
Grade 2+ AE
Week 48
Side effects of 2PR during the Choice period
Time Frame: Week 48
Grade 2+ AE
Week 48
Overall unintended IPV of DPP
Time Frame: Week 48
Intimate Partner Violence (IPV)
Week 48
Overall unintended IPV of 2PR
Time Frame: Week48
IPV
Week48
Unintended IPV of DPP during the crossover period
Time Frame: Week 24
IPV
Week 24
Unintended IPV of 2PR during the crossover period
Time Frame: Week 24
IPV
Week 24
Unintended IPV of DPP during the Choice period
Time Frame: Week 48
IPV
Week 48
Unintended IPV of 2PR during the Choice period
Time Frame: Week 48
IPV
Week 48
Overall unintended pregnancy of DPP
Time Frame: Week 48
Pregnancy
Week 48
Overall unintended pregnancy of 2PR
Time Frame: Week 48
Pregnancy
Week 48
Unintended pregnancy of DPP during the crossover period
Time Frame: Week 24
Pregnancy
Week 24
Unintended pregnancy of 2PR during the crossover period
Time Frame: Week 24
Pregnancy
Week 24
Compare unintended pregnancy of DPP during the Choice period
Time Frame: Week 48
Pregnancy
Week 48
Compare unintended pregnancy of 2PR during the Choice period
Time Frame: Week 48
Pregnancy
Week 48
Overall unintended HIV incidence of DPP
Time Frame: Week 48
HIV incidence
Week 48
Overall unintended HIV incidence of 2PR
Time Frame: Week 48
HIV incidence
Week 48
Unintended HIV incidence of DPP during the crossover period
Time Frame: Week 24
HIV incidence
Week 24
Unintended HIV incidence of 2PR during the crossover period
Time Frame: Week 24
HIV incidence
Week 24
Unintended HIV incidence of DPP during the Choice period
Time Frame: Week 48
HIV incidence
Week 48
Unintended HIV incidence of 2PR during the Choice period
Time Frame: Week 48
HIV incidence
Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
HIV Prevention Trials Network

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Lisa Haddad, MD, Population Council
  • Study Chair: Harriet Nuwagaba-Biribonwoha, MD, ICAP at Columbia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 15, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 15, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 17, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HPTN 104
  • UM1AI068619 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For studies within two years of primary objective(s) publication, de-identified individual participant data that underlie results in a publication will be provided upon request. For studies more than two years from the primary objective(s) publication, de-identified datasets will be available upon request (Public Use Datasets).

IPD Sharing Time Frame

Investigators may request de-identified datasets in order to duplicate published results, as required by specific journals. Otherwise, de-identified datasets will be made available upon request, two years following publication of the primary results manuscript.

IPD Sharing Access Criteria

Researchers aiming to duplicate published results or who provide a methodologically sound proposal for use of the data may submit a request for access to data that has informed published results by sending an email to HPTN-Data-Access@scharp.org. To access available de-identified datasets, investigators must complete the request form on the Atlas website. Researchers of approved requests will need to sign an HIV Prevention Trials Network (HPTN) Data Use Agreement before receiving the data and agree to use the provided acknowledgement statement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings