Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
Phase 3b, Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
2 other identifiers
interventional
1,104
4 countries
4
Brief Summary
The purpose of this study is to evaluate the maternal and infant safety of the dapivirine (DPV) vaginal ring (VR) and daily oral Truvada in HIV-uninfected pregnant women and their infants.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hiv-infections
Started Jan 2020
Typical duration for phase_3 hiv-infections
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2019
CompletedFirst Posted
Study publicly available on registry
May 29, 2019
CompletedStudy Start
First participant enrolled
January 9, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 13, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
May 13, 2024
CompletedResults Posted
Study results publicly available
August 12, 2025
CompletedAugust 12, 2025
May 1, 2025
4.3 years
May 24, 2019
May 13, 2025
July 24, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants With a Composite Safety Endpoint Adverse Event (AE)
All AEs were reported as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Composite safety endpoint AEs were AEs that were either categorized as serious adverse events (SAEs) or were Grade 3 or higher. This measure is the number of participants with at least one composite AE.
Measured through participant's last study visit. For mothers, this occurred at approximately Week 12 to 36, depending on participant's cohort, and for infants at approximately Week 52.
Pregnancy Outcomes
Frequency of different types of pregnancy outcomes among mothers.
Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
Secondary Outcomes (13)
Pregnancy Complications: Frequency of Pregnancy Complications
Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
Infant Drug Levels: Number of Infants With Detectable Infant Blood Tenofovir Diphosphate (TFV-DP)
Measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Blood Emtricitabine Triphosphate (FTC-TP)
measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Plasma DPV
measured at the 2-week post pregnancy outcome (PPO) visit
Adherence: Maternal Blood TFV-DP Concentrations
Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
- +8 more secondary outcomes
Study Arms (12)
Cohort 1 Mothers: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALParticipants in Cohort 1 (36 0/7 weeks - 37 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month. Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 1 Mothers: Truvada Tablet
EXPERIMENTALParticipants in Cohort 1 (36 0/7 weeks - 37 6/7 weeks) will take one Truvada oral tablet daily. Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 2 Mothers: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALParticipants in Cohort 2 (30 0/7 weeks - 35 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month. Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 2 Mothers: Truvada Tablet
EXPERIMENTALParticipants in Cohort 2 (30 0/7 weeks - 35 6/7 weeks) will take one Truvada oral tablet daily. Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 3 Mothers: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALParticipants in Cohort 3 (12 0/7 weeks - 29 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month. Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 3 Mothers: Truvada Tablet
EXPERIMENTALParticipants in Cohort 3 (12 0/7 weeks - 29 6/7 weeks) will take one Truvada oral tablet daily. Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
Cohort 1 Infants: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALInfants born to maternal participants in the Cohort 1 (36 0/7 weeks - 37 6/7 weeks) DPV VR arm.
Cohort 1 Infants: Truvada Tablet
EXPERIMENTALInfants born to maternal participants in the Cohort 1 (36 0/7 weeks - 37 6/7 weeks) Truvada oral tablet daily arm.
Cohort 2 Infants: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALInfants born to maternal participants in the Cohort 2 (30 0/7 weeks - 35 6/7 weeks) DPV VR arm.
Cohort 2 Infants: Truvada Tablet
EXPERIMENTALInfants born to maternal participants in the Cohort 2 (30 0/7 weeks - 35 6/7 weeks) Truvada oral tablet daily arm.
Cohort 3 Infants: Dapivirine (DPV) Vaginal Ring (VR)
EXPERIMENTALInfants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) DPV VR arm.
Cohort 3 Infants: Truvada Tablet
EXPERIMENTALInfants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) Truvada oral tablet daily arm.
Interventions
Vaginal ring containing 25 mg of DPV
Tablet taken orally
Eligibility Criteria
You may qualify if:
- Age 18 through 40 years (inclusive) at Enrollment, verified per site standard operating procedures (SOPs).
- At Enrollment, evidence of a viable, intrauterine, singleton pregnancy with sonographic confirmation, including for gestational age assessment.
- Note: If adequate (per judgment of Investigator of Record \[IoR\]/designee) sonographic results are not available from medical records at Screening, an ultrasound must be performed and results be available for review at Enrollment for all Cohorts. The ultrasound should be performed no later than the 36th week of gestation for Cohort 1 or the 28th week of gestation for Cohort 2.
- At Enrollment, pregnancy within gestational age limits of the currently enrolling cohort (per the study protocol).
- HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithm in the study protocol).
- At Screening and Enrollment, intending to continue her pregnancy until delivery.
- At Screening and Enrollment, intending to deliver at a health center or hospital where adequate records may be obtained, as defined in site SOPs.
- At Screening and Enrollment, willing to be randomized at time of enrollment to either of the two study arms, and to continue study product use until delivery.
- Able and willing to comply with all study requirements and complete all study procedures.
- Able and willing to provide the following:
- Informed consent for her and her infant to be screened for and to enroll in MTN-042, as defined in site SOPs.
- Adequate locator information, as defined in site SOPs.
- Adequate documentation of registration for antenatal care, as defined in site SOPs.
- Permission to contact participant's antenatal and postpartum care provider(s) and to obtain copies of antenatal and postpartum care records.
- At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation, unless approved by the Protocol Safety Review Team (PSRT).
You may not qualify if:
- Per participant report at Screening and/or Enrollment, intends to do any of the following during the study participation period:
- Use oral pre-exposure prophylaxis (PrEP) outside the context of study participation.
- Relocate away from the study site.
- Travel away from the study site for a time period that would interfere with study participation.
- At Screening or Enrollment, has a positive HIV test.
- At Screening or Enrollment, diagnosed with urinary tract infection (UTI), cervicitis, sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring treatment per World Health Organization (WHO) guidelines.
- At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.\*
- Participant report, clinical evidence and/or antenatal/medical care record of any of the following:
- Currently breastfeeding at Enrollment.
- Known adverse reaction to any of the study products (ever).
- Known adverse reaction to latex and polyurethane (ever).
- Symptoms suggestive of acute HIV infection at Screening or Enrollment.
- Non-therapeutic injection drug use in the 12 months prior to Enrollment.
- Use of HIV post-exposure prophylaxis (PEP) and/or PrEP during the current pregnancy.
- Participation in any other research study involving drugs, medical devices, vaginal products, or vaccines during the current pregnancy.
- +30 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Blantyre CRS (Johns Hopkins Research Project/College of Medicine)
Blantyre, Malawi
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001, South Africa
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
Kampala, Uganda
Zengeza CRS
Chitungwiza, Mashonaland East Province, Zimbabwe
Related Publications (2)
Fairlie L, Szydlo DW, Mayo A, Bunge K, Mhlanga F, Piper J, Dadabhai S, Gatsi VM, Horne E, Ssemambo PK, Mandiwa V, Mgodi NM, Owor M, Anderson PL, Marzinke MA, Nakabiito C, Scheckter R, Chappell C, Hillier SL; MTN-042 study team. Safety outcomes among infants whose mothers used the dapivirine vaginal ring or oral PrEP during pregnancy (MTN-042/DELIVER): a randomised phase 3b study. Lancet HIV. 2025 Nov;12(11):e763-e773. doi: 10.1016/S2352-3018(25)00261-9.
PMID: 41173578DERIVEDNansimbe J, Mirembe BG, Ssemambo PK, Ssekasi AM, Byogero R, Nalwoga J, Nakabiito C. Exploring pregnant women's experiences with dapivirine vaginal ring insertion during the MTN-042/DELIVER study in Uganda: a description of secondary data. Ther Adv Infect Dis. 2025 Apr 11;12:20499361251332750. doi: 10.1177/20499361251332750. eCollection 2025 Jan-Dec.
PMID: 40292084DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Daniel Szydlo
- Organization
- Fred Hutchinson Cancer Center
Study Officials
- STUDY CHAIR
Katherine Bunge, MD, MPH
University of Pittsburgh
- STUDY CHAIR
Felix Mhlanga, MBChB, MMed
Zengeza Clinical Research Site
- STUDY CHAIR
Lee Fairlie
Wits RHI Shandukani Research Centre
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 24, 2019
First Posted
May 29, 2019
Study Start
January 9, 2020
Primary Completion
May 13, 2024
Study Completion
May 13, 2024
Last Updated
August 12, 2025
Results First Posted
August 12, 2025
Record last verified: 2025-05