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

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: Not yet recruiting
• Conditions: HIV Infections; Pregnancy
• Intervention / Treatment: Drug: DPP; Drug: 2PR; Drug: Free Choice

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: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michelle Robinson; Phone Number: 919-321-3585; Email: mrobinson@fhi360.org
• Study Contact Backup: Name: Scott Rose; Phone Number: 919-321-3530; Email: srose@fhi360.org

Study Locations

• Eswatini
  • Mbabane, Eswatini
    • Eswatini Prevention Center CRS
    • Contact: Harriet Nuwagaba-Biribonwoha, MD, PhD; Phone Number: 268-76024678; Email: hn2158@cumc.columbia.edu
• Uganda
  • Kampala, Uganda
    • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
    • Contact: Clemensia Nakabiito, MD; Phone Number: 256-41-541044; Email: cnakabiito@mujhu.org
• Zimbabwe
  • Harare, Zimbabwe
    • Spilhaus CRS
    • Contact: Felix Mhlanga, MBChB, MMED; Phone Number: 263-772-335232; Email: fmhlanga@uz-ucsf.co.zw

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
PrEP adherence to DPP during randomized crossover period 1	Intraerythrocytic Tenofovir Diphosphate (TFV-DP) concentrations in dried blood spot (DBS)	Week 12
PrEP adherence to 2PR during randomized crossover period 1	Intraerythrocytic TFV-DP concentrations in DBS	Week 12
PrEP adherence to DPP during randomized crossover period 2	Intraerythrocytic TFV-DP concentrations in DBS	Week 24
PrEP adherence to 2PR during randomized crossover period 2	Intraerythrocytic TFV-DP concentrations in DBS	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PrEP adherence to DPP during Choice period	TFV-DP concentrations in DBS	Week 48
PrEP adherence to 2PR during Choice period	TFV-DP concentrations in DBS	Week 48
PrEP adherence to DPP during Choice period	Self-reported adherence	Week 48
PrEP adherence to 2PR during Choice period	Self-reported adherence	Week 48
Acceptability of DPP during crossover period	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	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	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	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	Preference of DPP at enrollment	Day 0
Preference for DPP	Preference of DPP at completion of the crossover phase of the study	Week 24
Preference for 2PR	Preference of 2PR at enrollment	Day 0
Preference for 2PR	Preference of 2PR at completion of the crossover phase of the study	Week 24
PrEP persistence on DPP during the Choice period	Proportion of participants still using their chosen regimen at end of the Choice period	Week 48
PrEP persistence on 2PR during the Choice period	Proportion of participants still using their chosen regimen at end of the Choice period	Week 48
Overall tolerability of DPP	Tolerability	Week 48
Overall tolerability of 2PR	Tolerability	Week 48
Tolerability of DPP during the crossover period	Tolerability	Week 24
Tolerability of 2PR during the crossover period	Tolerability	Week 24
Tolerability of DPP during the Choice period	Tolerability	Week 48
Tolerability of 2PR during the Choice period	Tolerability	Week 48
Overall side effects of DPP	Grade 2+ Adverse Events (AE)	Week 48
Overall side effects of 2PR	Grade 2+ AE	Week 48
Side effects of DPP during the crossover period	Grade 2+ AE	Week 24
Side effects of 2PR during the crossover period	Grade 2+ AE	Week 24
Side effects of DPP during the Choice period	Grade 2+ AE	Week 48
Side effects of 2PR during the Choice period	Grade 2+ AE	Week 48
Overall unintended IPV of DPP	Intimate Partner Violence (IPV)	Week 48
Overall unintended IPV of 2PR	IPV	Week48
Unintended IPV of DPP during the crossover period	IPV	Week 24
Unintended IPV of 2PR during the crossover period	IPV	Week 24
Unintended IPV of DPP during the Choice period	IPV	Week 48
Unintended IPV of 2PR during the Choice period	IPV	Week 48
Overall unintended pregnancy of DPP	Pregnancy	Week 48
Overall unintended pregnancy of 2PR	Pregnancy	Week 48
Unintended pregnancy of DPP during the crossover period	Pregnancy	Week 24
Unintended pregnancy of 2PR during the crossover period	Pregnancy	Week 24
Compare unintended pregnancy of DPP during the Choice period	Pregnancy	Week 48
Compare unintended pregnancy of 2PR during the Choice period	Pregnancy	Week 48
Overall unintended HIV incidence of DPP	HIV incidence	Week 48
Overall unintended HIV incidence of 2PR	HIV incidence	Week 48
Unintended HIV incidence of DPP during the crossover period	HIV incidence	Week 24
Unintended HIV incidence of 2PR during the crossover period	HIV incidence	Week 24
Unintended HIV incidence of DPP during the Choice period	HIV incidence	Week 48
Unintended HIV incidence of 2PR during the Choice period	HIV incidence	Week 48

Collaborators and Investigators

• Sponsor: HIV Prevention Trials Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Lisa Haddad, MD, Population Council; Study Chair: Harriet Nuwagaba-Biribonwoha, MD, ICAP at Columbia University

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): May 15, 2028

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Contraception; Pre-exposure Prophylaxis (PrEP); Pregnancy Prevention; Dual Prevention Pill (DPP)
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections
• Other Study ID 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