HIV InfectionsPhase 3NCT03965923
Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
A Phase 3 study testing Dapivirine (DPV) Vaginal Ring (VR) and Truvada Tablet in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Dapivirine (DPV) Vaginal Ring (VR) and Truvada Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,104 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 9 Jan 2020to 13 May 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- At Screening and Enrollment, intending to deliver at a health center or hospital where adequate records may be obtained, as defined in site SOPs.
- Note: Plans to deliver at a health center or hospital where adequate records may be obtained is inclusionary due to logistical challenges related to collection of vaginal rings (VRs), specimens and delivery outcome data outside of those settings.
- 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).
Who cannot join
- 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.
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- Note: Detection of bacterial vaginosis (BV) or candida in the absence of symptoms is not exclusionary. Otherwise eligible participants diagnosed during screening with a UTI, cervicitis, or STI/RTI requiring treatment per WHO guidelines are offered treatment consistent with WHO recommendations. If treatment is completed and symptoms have resolved within 35 days of obtaining informed consent for screening, the participant may be enrolled.
- At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.*
- Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the Investigator of Record (IoR)/designee is considered expected bleeding and is not exclusionary.
- 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.
- At Screening or Enrollment, known to have any of the following during the current pregnancy:
- Multiple gestation
- Placenta previa
- Cervical cerclage
- Abnormal fetal anatomy (in the opinion of the IoR or designee)
- Intrauterine growth restriction
- Pre-existing or gestational diabetes
- Hypertensive disorder of pregnancy
- Severe malaria
- Treatment for preterm labor
- Abnormal quantity of amniotic fluid (oligohydramnios or polyhydramnios)
- At Screening, known to have had any of the following in a previous pregnancy:
- Intrauterine growth restriction
- Gestational diabetes
- Hypertensive disorder of pregnancy
- Intrauterine fetal demise (estimated gestational age greater than or equal to 20 weeks)
- Delivery prior to 37 0/7 weeks
- At Enrollment, as determined by the IoR/designee, has any significant obstetrical complication (e.g., premature rupture of membranes, any abnormal placentation) or uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease that would make study participation unsafe.
- At Screening, has any of the following laboratory abnormalities:
- Positive for hepatitis B surface antigen (HBsAg).
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to Grade 1.**
- Hemoglobin greater than or equal to Grade 2.**
- Platelet count greater than or equal to Grade 1.**
- Creatinine greater than or equal to Grade 1.**
- Estimated creatinine clearance greater than or equal to Grade 2 (Cockcroft Gault formula).**
- Glycosuria greater than or equal to Grade 2.**
- Proteinuria greater than or equal to Grade 2.**
- Note: Otherwise eligible participants with an exclusionary test (other than HBsAg) may be re-tested during the screening process; re-testing procedure details can be found in the MTN-042 Study Specific Procedures (SSP) Manual. If improvement to a non-exclusionary grade or resolution is documented within 35 days of providing informed consent for screening, the participant may be enrolled.
- Has any condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- *Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
- **DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Malawi1 site
Blantyre CRS (Johns Hopkins Research Project/College of Medicine)
Blantyre
South Africa1 site
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001
About this study
Official title: Phase 3b, Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
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.
Read the detailed description
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.
Participants will be assigned to one of three cohorts based on gestational age:
- Cohort 1: 36 0/7 weeks - 37 6/7 weeks
- Cohort 2: 30 0/7 weeks - 35 6/7 weeks
- Cohort 3: 12 0/7 weeks - 29 6/7 weeks
Within each cohort, participants will be randomized to receive either DPV VR or oral Truvada. Participants randomized to the DPV VR will use the VR continuously for approximately one month, replacing the VR each month. Participants taking the Truvada tablet will take one tablet orally per day. Participants will use their assigned study product until their pregnancy outcome, but no later than 41 6/7 weeks of gestation.
Participants will attend several study visits throughout the study and study staff will also contact participants by phone at different timepoints throughout the study.
The total duration of study participation will vary depending on gestational age at time of enrollment and length of pregnancy prior to pregnancy outcome and will range from approximately 12 weeks or less for Cohort 1 to approximately 36 weeks or less for Cohort 3. Infants born to study participants will be followed for approximately 52 weeks.
- Conditions
- HIV Infections
- Being tested
- Dapivirine (DPV) Vaginal Ring (VR), Truvada Tablet
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapivirine (DPV) Vaginal Ring (VR)Drug
Vaginal ring containing 25 mg of DPV
Truvada TabletDrug
Also called Emtricitabine/Tenofovir Disoproxil Fumarate, FTC/TDF
Tablet taken orally
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Mothers: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Participants 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. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 1 Mothers: Truvada Tablet | Experimental | Participants 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. Receives: Drug: Truvada Tablet |
| Cohort 2 Mothers: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Participants 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. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 2 Mothers: Truvada Tablet | Experimental | Participants 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. Receives: Drug: Truvada Tablet |
| Cohort 3 Mothers: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Participants 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. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 3 Mothers: Truvada Tablet | Experimental | Participants 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. Receives: Drug: Truvada Tablet |
| Cohort 1 Infants: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Infants born to maternal participants in the Cohort 1 (36 0/7 weeks - 37 6/7 weeks) DPV VR arm. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 1 Infants: Truvada Tablet | Experimental | Infants born to maternal participants in the Cohort 1 (36 0/7 weeks - 37 6/7 weeks) Truvada oral tablet daily arm. Receives: Drug: Truvada Tablet |
| Cohort 2 Infants: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Infants born to maternal participants in the Cohort 2 (30 0/7 weeks - 35 6/7 weeks) DPV VR arm. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 2 Infants: Truvada Tablet | Experimental | Infants born to maternal participants in the Cohort 2 (30 0/7 weeks - 35 6/7 weeks) Truvada oral tablet daily arm. Receives: Drug: Truvada Tablet |
| Cohort 3 Infants: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Infants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) DPV VR arm. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR) |
| Cohort 3 Infants: Truvada Tablet | Experimental | Infants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) Truvada oral tablet daily arm. Receives: Drug: Truvada Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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
Frequency of different types of pregnancy complications among mothers.
The categories of pregnancy complications were pre-defined on the case report form, and after the completion of Cohort 1 follow-up there were some changes made to the pregnancy complication categories. In Cohort 1 the category "peripartum hemorrhage" was collected, but in Cohort 2 and 3 this category was removed from the list of pre-defined complications. Two other categories, "antepartum hemorrhage" and "intrapartum hemorrhage", were added to the list for Cohort 2 and Cohort 3. As a result, participants in Cohort 1 were not evaluated for antepartum or intrapartum hemorrhage, while participants in Cohorts 2 and 3 were not evaluated for peripartum hemorrhage. All other complications were collected for all three cohorts, and participants in all three cohorts were evaluated for each complication.
Measured: 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)
Infant blood TFV-DP was measured at infants' post pregnancy outcome (PPO) visit (up to 14 days after pregnancy outcome). The outcome is defined as having detectable drug level, with detectable drug levels defined as a TFV-DP concentration above the lower limit of quantification (LLOQ) for the assay.
Measured: Measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Blood Emtricitabine Triphosphate (FTC-TP)
Infant blood FTC-TP was measured at infants' PPO visit. The outcome is defined as having detectable drug level, with detectable drug levels defined as a FTC-TP concentration above the lower limit of quantification (LLOQ) for the assay.
Measured: measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Plasma DPV
Infant plasma DPV concentration was measured at infants' post pregnancy outcome (PPO) visit (up to 14 days after pregnancy outcome). The outcome is defined as having detectable drug level, with detectable drug levels defined as a DPV concentration above the lower limit of quantification (LLOQ) for the assay.
Measured: measured at the 2-week post pregnancy outcome (PPO) visit
Adherence: Maternal Blood TFV-DP Concentrations
Maternal blood TFV-DP was collected at the 2-week, bi-weekly (starting at 4-weeks), and PPO visits for participants randomized to receive Truvada Tablet. In Cohort 1 this was done for a randomly selected subset of those participants. Participants are categorized as ever being exposed if they had at least one measure that was >= 200 fmol/punch (if the sample was collected more than 6 weeks after randomization) or >= 150 fmol/punch (if the sample was collected within 6 weeks of randomization). They are categorized as never being exposed if they had at least one analyzable sample and none met the criteria.
Measured: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Maternal Blood FTC-TP Concentrations
Maternal blood FTC-TP was collected at the 2-week, bi-weekly (starting at 4-weeks), and PPO visits for participants randomized to receive Truvada Tablet. In Cohort 1 this was done for a randomly selected subset of those participants.
Measured: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Maternal Plasma DPV Concentrations
Maternal plasma DPV was collected at the 2-week, bi-weekly (starting at 4-weeks), and PPO visits for a randomly selected subset of participants (approximately 50%) randomized to receive the VR. Participants are categorized as ever being exposed if they had at least one measure that was greater than the LLOQ (i.e., greater than or equal to 20 pg/mL). They are categorized as never being exposed if they had at least one analyzable sample and none met the criteria.
Measured: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Frequency of Missing Taking the Pills
Based on participant report, as defined by self-reported missed doses for oral Truvada. This was only reported by participants in Cohorts 2 and 3.
Measured: Measured at Week 4 and PPO visits
Adherence: Number of Participants With Product Exposure (Measured in Residual Drug Levels in Returned VRs)
Residual drug levels were collected from returned VRs, which were expected to be returned at monthly visits throughout study follow-up. Drug release rate was calculated by subtracting the residual level from the amount of residual drug in the manufacturer lot, divided by the number of days the participant was expected to use that ring, times 28 days. For each individual ring, a ring was considered to show evidence of use if the residual drug level was greater than or equal to 0.9mg/28 days of use.
Participants are categorized as either ever being exposed or never being exposed to product over the course of study follow-up. They are categorized as ever being exposed to product if they had at least one ring with evidence of use (i.e., greater than or equal to 0.9 mg/28 days of release). They are categorized as never being exposed if they had at least one analyzable returned ring and none of these rings had evidence of use.
Measured: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
Acceptability: Participant Willingness to Use Study Products During Pregnancy in the Future
Based on participant report of whether they would be willing to use the study product they were randomized to receive when pregnant in the future. Only asked of participants in Cohorts 2 and 3.
Measured: Measured at Week 4 and 6-Week PPO/SEV visits.
Acceptability: Participants Who Find the Study Products to be at Least as Acceptable as Other HIV Prevention Methods
Based on participant report of how much they liked or disliked the study product they were randomized to receive for HIV prevention, and of how much they liked or disliked male condoms for HIV prevention. Only asked of participants in Cohorts 2 and 3.
Measured: Measured at Week 4 visits.
Adherence: Frequency of Ring Removal/Expulsion
Based on participant report, as defined by self-reported occurrences of the ring being out of the vagina for more than 12 hours, being out for any time. This was only reported by participants in Cohorts 2 and 3.
Measured: Measured at Week 4 visit and Post-Pregnancy Outcome (PPO) (occurring within 2 weeks of pregnancy outcome) visit
Acceptability: Participants Who Are Satisfied With the Study Products for Preventing HIV
Based on participant report of how satisfied they have been with the the study product they were randomized to receive for HIV prevention. Only asked of participants in Cohorts 2 and 3.
Measured: Measured at Week 4 visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2019
- Study start9 Jan 2020
- Primary completion13 May 2024
- Study completion13 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1,104 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Katherine Bunge, MD, MPH, Study chair, University of PittsburghFelix Mhlanga, MBChB, MMed, Study chair, Zengeza Clinical Research SiteLee Fairlie, Study chair, Wits RHI Shandukani Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03965923
- Sponsor's protocol ID
- MTN-042
- Other IDs
- 38544
- Status last verified
- May 2025
- First submitted
- 24 May 2019
- Last updated
- 12 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mhlanga FG, Szydlo DW, Mayo AJ, Bunge K, Fairlie L, Nakabiito C, Musara P, Mgodi NM, Dadabhai S, Scheckter R, Anderson PL, Marzinke MA, Chappell C, Gadama LA, Richardson BA, Piper JM, Hillier SL; MTN-042 DELIVER study team. Safety, acceptability, and adherence to dapivirine vaginal ring and oral pre-exposure prophylaxis for HIV prevention in the second trimester of pregnancy: a multicountry, open-label, phase 3b randomised trial. Lancet HIV. 2026 Mar;13(3):e176-e184. doi: 10.1016/S2352-3018(25)00307-8. Epub 2026 Feb 10.
PubMed 41687672Fairlie 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.
PubMed 41173578Nansimbe 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.
PubMed 40292084
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3b, Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
- ClinicalTrials.gov ID
- NCT03965923
- Acronym / sponsor ID
- MTN-042
- Conditions
- HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,104 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 9 Jan 2020 (actual)
- Primary completion
- 13 May 2024 (actual)
- Study completion
- 13 May 2024 (actual)
- First posted
- 29 May 2019 (actual)
- Results
- Posted 12 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Participants will be assigned to one of three cohorts based on gestational age:
- Cohort 1: 36 0/7 weeks - 37 6/7 weeks
- Cohort 2: 30 0/7 weeks - 35 6/7 weeks
- Cohort 3: 12 0/7 weeks - 29 6/7 weeks
Within each cohort, participants will be randomized to receive either DPV VR or oral Truvada. Participants randomized to the DPV VR will use the VR continuously for approximately one month, replacing the VR each month. Participants taking the Truvada tablet will take one tablet orally per day. Participants will use their assigned study product until their pregnancy outcome, but no later than 41 6/7 weeks of gestation.
Participants will attend several study visits throughout the study and study staff will also contact participants by phone at different timepoints throughout the study.
The total duration of study participation will vary depending on gestational age at time of enrollment and length of pregnancy prior to pregnancy outcome and will range from approximately 12 weeks or less for Cohort 1 to approximately 36 weeks or less for Cohort 3. Infants born to study participants will be followed for approximately 52 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Mothers: Dapivirine (DPV) Vaginal Ring (VR) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Participants 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 | Experimental | Drug: Truvada TabletParticipants 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) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Participants 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 | Experimental | Drug: Truvada TabletParticipants 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) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Participants 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 | Experimental | Drug: Truvada TabletParticipants 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) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Infants born to maternal participants in the Cohort 1 (36 0/7 weeks - 37 6/7 weeks) DPV VR arm. |
| Cohort 1 Infants: Truvada Tablet | Experimental | Drug: Truvada TabletInfants 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) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Infants born to maternal participants in the Cohort 2 (30 0/7 weeks - 35 6/7 weeks) DPV VR arm. |
| Cohort 2 Infants: Truvada Tablet | Experimental | Drug: Truvada TabletInfants 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) | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)Infants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) DPV VR arm. |
| Cohort 3 Infants: Truvada Tablet | Experimental | Drug: Truvada TabletInfants born to maternal participants in the Cohort 3 (12 0/7 weeks - 29 6/7 weeks) Truvada oral tablet daily arm. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- 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.
- 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.
Key exclusion criteria (48 listed)
- Per participant report at Screening and/or Enrollment, intends to do any of the following during the study participation period:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapivirine (DPV) Vaginal Ring (VR)Vaginal ring containing 25 mg of DPV | Drug | Cohort 1 Infants: Dapivirine (DPV) Vaginal Ring (VR), Cohort 1 Mothers: Dapivirine (DPV) Vaginal Ring (VR), Cohort 2 Infants: Dapivirine (DPV) Vaginal Ring (VR), Cohort 2 Mothers: Dapivirine (DPV) Vaginal Ring (VR), Cohort 3 Infants: Dapivirine (DPV) Vaginal Ring (VR), Cohort 3 Mothers: Dapivirine (DPV) Vaginal Ring (VR) |
| Truvada TabletAlso: Emtricitabine/Tenofovir Disoproxil Fumarate, FTC/TDFTablet taken orally | Drug | Cohort 1 Infants: Truvada Tablet, Cohort 1 Mothers: Truvada Tablet, Cohort 2 Infants: Truvada Tablet, Cohort 2 Mothers: Truvada Tablet, Cohort 3 Infants: Truvada Tablet, Cohort 3 Mothers: Truvada Tablet |
Primary outcome
Number of Participants With a Composite Safety Endpoint Adverse Event (AE)
Time frame: 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.
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.
Pregnancy Outcomes
Time frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
Frequency of different types of pregnancy outcomes among mothers.
13 secondary outcomes
Pregnancy Complications: Frequency of Pregnancy Complications
Time frame: 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)
Time frame: Measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Blood Emtricitabine Triphosphate (FTC-TP)
Time frame: measured at the 2-week post pregnancy outcome (PPO) visit
Infant Drug Levels: Number of Infants With Detectable Plasma DPV
Time frame: measured at the 2-week post pregnancy outcome (PPO) visit
Adherence: Maternal Blood TFV-DP Concentrations
Time frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Maternal Blood FTC-TP Concentrations
Time frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Maternal Plasma DPV Concentrations
Time frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
Adherence: Frequency of Missing Taking the Pills
Time frame: Measured at Week 4 and PPO visits
Adherence: Number of Participants With Product Exposure (Measured in Residual Drug Levels in Returned VRs)
Time frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
Acceptability: Participant Willingness to Use Study Products During Pregnancy in the Future
Time frame: Measured at Week 4 and 6-Week PPO/SEV visits.
Acceptability: Participants Who Find the Study Products to be at Least as Acceptable as Other HIV Prevention Methods
Time frame: Measured at Week 4 visits.
Adherence: Frequency of Ring Removal/Expulsion
Time frame: Measured at Week 4 visit and Post-Pregnancy Outcome (PPO) (occurring within 2 weeks of pregnancy outcome) visit
Acceptability: Participants Who Are Satisfied With the Study Products for Preventing HIV
Time frame: Measured at Week 4 visits.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41687672Mhlanga FG, Szydlo DW, Mayo AJ, Bunge K, Fairlie L, Nakabiito C, Musara P, Mgodi NM, Dadabhai S, Scheckter R, Anderson PL, Marzinke MA, Chappell C, Gadama LA, Richardson BA, Piper JM, Hillier SL; MTN-042 DELIVER study team. Safety, acceptability, and adherence to dapivirine vaginal ring and oral pre-exposure prophylaxis for HIV prevention in the second trimester of pregnancy: a multicountry, open-label, phase 3b randomised trial. Lancet HIV. 2026 Mar;13(3):e176-e184. doi: 10.1016/S2352-3018(25)00307-8. Epub 2026 Feb 10.
- Derived from this study: PubMed 41173578Fairlie 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.
- Derived from this study: PubMed 40292084Nansimbe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Bunge, MD, MPH study chair
University of Pittsburgh
Felix Mhlanga, MBChB, MMed study chair
Zengeza Clinical Research Site
Lee Fairlie study chair
Wits RHI Shandukani Research Centre
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dapivirine (DPV) Vaginal Ring (VR) and Truvada Tablet in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Malawi, South Africa, Uganda, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Composite Safety Endpoint Adverse Event (AE) (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03965923, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.