HIV InfectionsPhase 3NCT04140266
Safety and Drug Detection Study of Dapivirine Vaginal Ring and Oral TRUVADA® in Breastfeeding Mother-Infant Pairs
A Phase 3 study testing Dapivirine (DPV) Vaginal Ring (VR)-004 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 safety and drug detection of the dapivirine vaginal ring and oral Truvada in breastfeeding mother-infant pairs. Read more about this study
- Who is it for?
- Ages 6 weeks and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Dapivirine (DPV) Vaginal Ring (VR)-004 and Truvada Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 394 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 24 Sep 2020to 4 Nov 2021
- 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 6 weeks and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Participant mothers must meet all the following criteria to be eligible for inclusion in the study:
- Age 18 years or older at Screening, as verified per site Standard Operating Procedures (SOPs).
- At Enrollment, between 6 to 12 weeks postpartum (verified by birth records and/or similar supportive documentation and defined as between 42 - 84 days after delivery, inclusive).
- By participant report at Screening and Enrollment, currently exclusively breastfeeding one infant and willing and able to continue exclusively breastfeeding that infant for the duration of their participation in the study.
- Note: Exclusive breastfeeding will be defined as infant nutrition solely from breast milk, as determined by 7-day recall breastfeeding history. For the purposes of MTN-043, "breastfeeding" refers to all human milk feeding situations when an infant is fed with participant's own human milk whether the milk is received directly from the breast or as expressed milk.
- Consistently using an effective method of contraception per participant report at Enrollment, and intending to continue use of an effective method for the duration of study participation. Effective methods include contraceptive implants, intrauterine device, injectable progestin, oral contraceptive pills, and surgical sterilization.
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- Able and willing to comply with all study requirements and complete all study procedures.
- Able and willing to provide the following:
- Written informed consent to be screened for and to take part in the study.
- Written informed consent for the breastfed infant to be screened for and take part in the study.
- Intention to stay within study catchment area for study duration and willingness to give adequate locator information, as defined in site SOPs.
- At Screening and Enrollment, HIV-uninfected based on HIV testing performed by study staff (per algorithm in the study protocol).
- At Screening and Enrollment, willing to be randomized at time of enrollment to either of the study products, and to continue study product use for at least 12 weeks.
- Each mother eligible for MTN-043 will be asked to provide written informed consent for herself and her infant to participate in the study if the infant meets the following criteria:
- At Screening and Enrollment, infant is exclusively breastfed.
- Note: Exclusive breastfeeding will be defined as infant nutrition solely from breast milk, as determined by 7-day recall breastfeeding history. For the purposes of MTN-043, "breastfeeding" refers to all human milk feeding situations when an infant is fed with participant's own human milk whether the milk is received directly from the breast or as expressed milk.
- At Screening and Enrollment, the infant is generally healthy, according to the judgment of the investigator of record (IoR)/designee.
- At Enrollment, the infant is between the ages of 6 and 12 weeks postpartum (verified by birth records and/or similar supportive documentation with age defined as between 42 - 84 days after delivery, inclusive).
Who cannot join
- Mothers who meet any of the following criteria will be excluded from the study:
- At Screening or Enrollment, breastfeeding infant ineligible for enrollment in the study.
- At Screening or Enrollment, participant reports any of the following:
- Known adverse reaction to any of the study products (ever).
- Known adverse reaction to latex and polyurethane (ever).
- Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to Enrollment.
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- Use of vaginal medications(s) or other vaginal products within five days prior to Enrollment.
- Non-therapeutic injection drug use in the 12 months prior to Enrollment.
- History of exposure to any investigational drug(s) during pregnancy, including participation in MTN-042.
- At Screening or Enrollment, has a positive HIV test.
- At Screening or Enrollment, Grade 2 or higher breast or genitourinary findings.
- At Screening or Enrollment, has a positive urinary pregnancy test.
- At Screening, has any of the following laboratory abnormalities:
- Positive for hepatitis B surface antigen (HBsAg).
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ Grade 2.
- Creatinine ≥ Grade 1.
- Estimated creatinine clearance ≥ Grade 2 (Cockcroft Gault formula).
- Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), sexually transmitted infection (STI) or reproductive tract infection (RTI), requiring treatment per World Health Organization (WHO) Guidelines.
- Note: Otherwise eligible participants diagnosed during Screening with a UTI, PID or STI/RTI requiring treatment per WHO Guidelines - other than asymptomatic bacterial vaginosis (BV) and asymptomatic vulvovaginal candidiasis - are offered treatment consistent with WHO recommendations and may be enrolled after completing treatment if all symptoms have resolved. If treatment is completed and symptoms have resolved prior to obtaining informed consent for Screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to enrollment. Genital warts requiring treatment are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.
- As determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease.
- Has any other 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.
- At Enrollment, participant reports any of the following:
- Participation in any research study involving drugs, vaccines, or medical devices 30 days or less prior to enrollment.
- Currently participating in other research studies involving drugs, vaccines, or medical devices.
- Expected to participate in other research studies involving drugs, vaccines, or medical devices during study participation.
- Has any condition that, in the opinion of the IoR/designee, would preclude eligibility, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- Note: Examples of exclusionary infant conditions include clinical evidence of stunting or illness.
- At Enrollment, according to the report of the mother, any of the following apply for the infant:
- Infants with birth weight less than 2000g.
- Participation in any research study involving drugs, vaccines, or medical devices since birth.
- Currently participating in other research studies involving drugs, vaccines, or medical devices.
- Expected to participate in other research studies involving drugs, vaccines, or medical devices for the duration of study participation.
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, and Drug Detection Study of Dapivirine Vaginal Ring and Oral TRUVADA® in Breastfeeding Mother-Infant Pairs
The purpose of this study is to evaluate the safety and drug detection of the dapivirine vaginal ring and oral Truvada in breastfeeding mother-infant pairs.
Read the detailed description
This study will evaluate the safety and drug detection of the dapivirine (DPV) vaginal ring (VR) and oral Truvada in breastfeeding mother-infant pairs.
Mother-infant pairs will be randomly assigned to receive either the DPV VR or oral Truvada. Mothers randomized to the DPV VR will use the VR continuously for approximately one month (4 weeks), replacing the VR each month for approximately three months (12 weeks). Mothers using the Truvada tablet will take one tablet by mouth daily for approximately three months (12 weeks).
Study visits will occur at Day 0, Weeks 1 and 2, and Months 1, 2, 3, and 3.5. Study visits may include behavioral assessments; product acceptability assessments; infant feeding assessments; physical examinations; blood, urine, and breast milk collection; and pelvic examination and specimen collection.
- Conditions
- HIV Infections
- Being tested
- Dapivirine (DPV) Vaginal Ring (VR)-004, 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)-004Drug
Vaginal ring containing 25 mg of DPV
Truvada TabletDrug
Also called Emtricitabine/Tenofovir Disoproxil Fumarate, FTC/TDF
Oral tablet containing 200 mg emtricitabine (FTC)/300 mg tenofovir disoproxil fumarate (TDF)
| Study group | Role | What they receive |
|---|---|---|
| Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Experimental | Mothers will use one DPV VR continuously for approximately one month, replacing the DPV VR each month for approximately three months. Receives: Drug: Dapivirine (DPV) Vaginal Ring (VR)-004 |
| Group B: Truvada Tablet | Experimental | Mothers will take one Truvada oral tablet daily for approximately three months. Receives: Drug: Truvada Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms
As defined by the Manual for Expedited Reporting of Adverse Events to the Division of AIDS (DAIDS) (Version 2.0, January 2010)
Measured: Measured through Month 3.5
Number of Mother Participants With Grade 3 or Higher Adverse Events (AEs) in Both Study Arms
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
Measured: Measured through Month 3.5
Number of Infant Participants With SAEs Including Infant Deaths in Both Study Arms
As defined by the Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0, January 2010)
Measured: Measured through Month 3.5
Number of Infant Participants With Grade 3 or Higher AEs in Both Study Arms
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from mother participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in plasma, the LLOQ is 20 pg/ml. The infant endpoint is included as a separate section below.
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. FTC-TP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC-TP concentration in DBS specimens, the LLOQ is 0.125 pmol/punch. The infant endpoint is included as a separate section below.
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. TFV-DP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV-DP concentrations, the LLOQ is 31.3 fmol/punch. The infant endpoint is included as a separate section below.
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations
This endpoint is based on DPV concentration laboratory results from evaluable breastmilk specimens from mother participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in breastmilk, the LLOQ is 10 pg/ml.
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations
This endpoint is based on FTC concentration laboratory results from evaluable breastmilk specimens from mother participants. FTC concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC concentrations in breastmilk, the LLOQ is 5 mg/ml.
Measured: Measured through Month 3.5
Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations
This endpoint is based on TFV concentration laboratory results from evaluable breastmilk specimens from mother participants. TFV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV concentrations in breastmilk, the LLOQ is 1 ng/ml.
Measured: Measured through Month 3.5
Number and Proportion of Infants With Detectable Plasma DPV Concentrations
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from infant participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in plasma, the LLOQ is 20 pg/ml. The mother endpoints are included as separate sections above.
Measured: Measured through Month 3.5
Number and Proportion of Infants With Detectable FTC-TP Concentrations
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. FTC-TP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC-TP concentrations from DBS specimens, the LLOQ is 0.125 pmol/punch. The mother endpoints are included as separate sections above.
Measured: Measured through Month 3.5
Number and Proportion of Infants With Detectable TFV-DP Concentrations
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. TFV-DP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV-DP concentrations from DBS specimens, the LLOQ is 31.3 fmol/punch. The mother endpoints are included as separate sections above.
Measured: Measured through Month 3.5
Geometric Mean of Maternal DPV Concentrations From Plasma by Visit
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (20pg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Maternal FTC-TP Concentrations by Visit
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (0.125 pmol/punch). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Maternal TFV-DP Concentrations by Visit
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (31.3 fmol/punch). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit
This endpoint is based on DPV concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (10pg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit
This endpoint is based on FTC concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (5 mg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit
This endpoint is based on TFV concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (1 ng/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Measured: Measured through Month 3.5
Geometric Mean of Infant DPV Concentrations From Plasma by Visit
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (20pg/ml). The mother endpoints for geometric mean concentrations are included as separate sections above.
Measured: Measured through Month 3.5
Geometric Mean of Infant FTC-TP Concentration by Visit
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (0.125 pmol/punch). The mother endpoints for geometric mean concentrations are included as separate sections above.
Measured: Measured through Month 3.5
Geometric Mean of Infant TFV-DP Concentrations by Visit
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (31.3 fmol/punch). The mother endpoints for geometric mean concentrations are included as separate sections above.
Measured: Measured through Month 3.5
Secondary outcomes (4)
The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product
The number and proportion of mother's visits with drug concentration indicative of non-adherence (no use) are reported by study month. Non-adherence is measured by residual drug in returned VRs for mothers assigned the DPV VR arm and by TFV-DP concentrations in dried blood spot specimens for mothers assigned the Truvada tablet arm. For mothers on the DPV VR arm, no use is defined as residual DPV concentration in the returned VRs <= 0.9mg/month. For mothers on the Truvada arm, no use is defined as TFV-DP concentrations < 16.6 fmol/punch. Only mother participants are included in this endpoint since infants did not directly use study product in this study.
Measured: Measured through Month 3
Residual Drug Levels in Returned VRs
The residual DPV concentrations from the returned VRs are summarized.
Measured: Measured through Month 3.5
Participant Willingness to Use Their Assigned Study Products During Breastfeeding in the Future (Y/N)
Based on participant report to the question "Would you be willing to use the study product for HIV prevention while breastfeeding in the future?"
Measured: Measured through Month 3.5
Proportion of Participants Who Find Their Study Product to be at Least as Acceptable as Other HIV Prevention Methods
Based on participant report on the question "Overall, how much did you like using the study product?" on the Product End Use Visit Behavioral Assessment.
Measured: Measured through Month 3.5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study start24 Sep 2020
- Primary completion4 Nov 2021
- Study completion4 Nov 2021
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 (1)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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Maxensia Owor, MBChB, MMed, MPH, Study chair, MU-JHU CARELisa Noguchi, PhD, CNM, Study chair, Johns Hopkins Bloomberg School of Public HealthJen Balkus, PhD, MPH, Study chair, Hans Rosling Center for Population Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04140266
- Sponsor's protocol ID
- MTN-043
- Other IDs
- 38591
- Status last verified
- Jul 2023
- First submitted
- 24 Oct 2019
- Last updated
- 4 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be made available to researchers upon request. The IPD to be shared will be negotiated with the researchers
Publications
Noguchi LM, Owor M, Mgodi NM, Gati Mirembe B, Dadabhai S, Horne E, Gundacker H, Richardson BA, Bunge K, Scheckter R, Song M, Marzinke MA, Anderson PL, Livant E, Jacobson C, Piper JM, Chakhtoura N, Hillier SL, Balkus JE; MTN-043 Study Team. Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother-infant pairs (MTN-043): a phase 3B, open-label, randomised trial. Lancet HIV. 2025 Mar;12(3):e180-e190. doi: 10.1016/S2352-3018(24)00306-0. Epub 2025 Feb 12.
PubMed 39954697
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3B, Randomized, Open-Label, Safety, and Drug Detection Study of Dapivirine Vaginal Ring and Oral TRUVADA® in Breastfeeding Mother-Infant Pairs
- ClinicalTrials.gov ID
- NCT04140266
- Acronym / sponsor ID
- MTN-043
- Conditions
- HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 394 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 4 Nov 2021 (actual)
- Study completion
- 4 Nov 2021 (actual)
- First posted
- 25 Oct 2019 (actual)
- Results
- Posted 4 Aug 2023
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 safety and drug detection of the dapivirine vaginal ring and oral Truvada in breastfeeding mother-infant pairs.
Detailed description
This study will evaluate the safety and drug detection of the dapivirine (DPV) vaginal ring (VR) and oral Truvada in breastfeeding mother-infant pairs.
Mother-infant pairs will be randomly assigned to receive either the DPV VR or oral Truvada. Mothers randomized to the DPV VR will use the VR continuously for approximately one month (4 weeks), replacing the VR each month for approximately three months (12 weeks). Mothers using the Truvada tablet will take one tablet by mouth daily for approximately three months (12 weeks).
Study visits will occur at Day 0, Weeks 1 and 2, and Months 1, 2, 3, and 3.5. Study visits may include behavioral assessments; product acceptability assessments; infant feeding assessments; physical examinations; blood, urine, and breast milk collection; and pelvic examination and specimen collection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Experimental | Drug: Dapivirine (DPV) Vaginal Ring (VR)-004Mothers will use one DPV VR continuously for approximately one month, replacing the DPV VR each month for approximately three months. |
| Group B: Truvada Tablet | Experimental | Drug: Truvada TabletMothers will take one Truvada oral tablet daily for approximately three months. |
Who may qualify
- Ages
- 6 weeks and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Participant mothers must meet all the following criteria to be eligible for inclusion in the study:
- Age 18 years or older at Screening, as verified per site Standard Operating Procedures (SOPs).
- At Enrollment, between 6 to 12 weeks postpartum (verified by birth records and/or similar supportive documentation and defined as between 42 - 84 days after delivery, inclusive).
- By participant report at Screening and Enrollment, currently exclusively breastfeeding one infant and willing and able to continue exclusively breastfeeding that infant for the duration of their participation in the study.
- Consistently using an effective method of contraception per participant report at Enrollment, and intending to continue use of an effective method for the duration of study participation. Effective methods include contraceptive implants, intrauterine device, injectable progestin, oral contraceptive pills, and surgical sterilization.
Key exclusion criteria (32 listed)
- At Screening or Enrollment, breastfeeding infant ineligible for enrollment in the study.
- At Screening or Enrollment, participant reports any of the following:
- At Screening or Enrollment, has a positive HIV test.
- At Screening or Enrollment, Grade 2 or higher breast or genitourinary findings.
- At Screening or Enrollment, has a positive urinary pregnancy test.
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)-004Vaginal ring containing 25 mg of DPV | Drug | Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 |
| Truvada TabletAlso: Emtricitabine/Tenofovir Disoproxil Fumarate, FTC/TDFOral tablet containing 200 mg emtricitabine (FTC)/300 mg tenofovir disoproxil fumarate (TDF) | Drug | Group B: Truvada Tablet |
Primary outcome
Number of Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms
Time frame: Measured through Month 3.5
As defined by the Manual for Expedited Reporting of Adverse Events to the Division of AIDS (DAIDS) (Version 2.0, January 2010)
Number of Mother Participants With Grade 3 or Higher Adverse Events (AEs) in Both Study Arms
Time frame: Measured through Month 3.5
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
Number of Infant Participants With SAEs Including Infant Deaths in Both Study Arms
Time frame: Measured through Month 3.5
As defined by the Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0, January 2010)
Number of Infant Participants With Grade 3 or Higher AEs in Both Study Arms
Time frame: Measured through Month 3.5
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from mother participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in plasma, the LLOQ is 20 pg/ml. The infant endpoint is included as a separate section below.
Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. FTC-TP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC-TP concentration in DBS specimens, the LLOQ is 0.125 pmol/punch. The infant endpoint is included as a separate section below.
Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. TFV-DP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV-DP concentrations, the LLOQ is 31.3 fmol/punch. The infant endpoint is included as a separate section below.
Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable breastmilk specimens from mother participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in breastmilk, the LLOQ is 10 pg/ml.
Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on FTC concentration laboratory results from evaluable breastmilk specimens from mother participants. FTC concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC concentrations in breastmilk, the LLOQ is 5 mg/ml.
Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on TFV concentration laboratory results from evaluable breastmilk specimens from mother participants. TFV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV concentrations in breastmilk, the LLOQ is 1 ng/ml.
Number and Proportion of Infants With Detectable Plasma DPV Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from infant participants. DPV concentrations above the lower limit of quantification (LLOQ) are considered detectable. For DPV concentration in plasma, the LLOQ is 20 pg/ml. The mother endpoints are included as separate sections above.
Number and Proportion of Infants With Detectable FTC-TP Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. FTC-TP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For FTC-TP concentrations from DBS specimens, the LLOQ is 0.125 pmol/punch. The mother endpoints are included as separate sections above.
Number and Proportion of Infants With Detectable TFV-DP Concentrations
Time frame: Measured through Month 3.5
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. TFV-DP concentrations above the lower limit of quantification (LLOQ) are considered detectable. For TFV-DP concentrations from DBS specimens, the LLOQ is 31.3 fmol/punch. The mother endpoints are included as separate sections above.
Geometric Mean of Maternal DPV Concentrations From Plasma by Visit
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (20pg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Maternal FTC-TP Concentrations by Visit
Time frame: Measured through Month 3.5
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (0.125 pmol/punch). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Maternal TFV-DP Concentrations by Visit
Time frame: Measured through Month 3.5
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (31.3 fmol/punch). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (10pg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit
Time frame: Measured through Month 3.5
This endpoint is based on FTC concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (5 mg/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit
Time frame: Measured through Month 3.5
This endpoint is based on TFV concentration laboratory results from evaluable breastmilk specimens from mother participants. The geometric mean is summarized by study visit and includes only mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (1 ng/ml). The infant endpoints for geometric mean concentrations are included as separate sections below.
Geometric Mean of Infant DPV Concentrations From Plasma by Visit
Time frame: Measured through Month 3.5
This endpoint is based on DPV concentration laboratory results from evaluable plasma specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the DPV VR arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (20pg/ml). The mother endpoints for geometric mean concentrations are included as separate sections above.
Geometric Mean of Infant FTC-TP Concentration by Visit
Time frame: Measured through Month 3.5
This endpoint is based on FTC-TP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (0.125 pmol/punch). The mother endpoints for geometric mean concentrations are included as separate sections above.
Geometric Mean of Infant TFV-DP Concentrations by Visit
Time frame: Measured through Month 3.5
This endpoint is based on TFV-DP concentration laboratory results from evaluable dried blood spot (DBS) specimens from infant participants. The geometric mean is summarized by study visit and includes only infants of mothers randomized to the Truvada arm. A value of 1/2 of the LLOQ is used if the concentration falls below the LLOQ (31.3 fmol/punch). The mother endpoints for geometric mean concentrations are included as separate sections above.
4 secondary outcomes
The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product
Time frame: Measured through Month 3
Residual Drug Levels in Returned VRs
Time frame: Measured through Month 3.5
Participant Willingness to Use Their Assigned Study Products During Breastfeeding in the Future (Y/N)
Time frame: Measured through Month 3.5
Proportion of Participants Who Find Their Study Product to be at Least as Acceptable as Other HIV Prevention Methods
Time frame: Measured through Month 3.5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39954697Noguchi LM, Owor M, Mgodi NM, Gati Mirembe B, Dadabhai S, Horne E, Gundacker H, Richardson BA, Bunge K, Scheckter R, Song M, Marzinke MA, Anderson PL, Livant E, Jacobson C, Piper JM, Chakhtoura N, Hillier SL, Balkus JE; MTN-043 Study Team. Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother-infant pairs (MTN-043): a phase 3B, open-label, randomised trial. Lancet HIV. 2025 Mar;12(3):e180-e190. doi: 10.1016/S2352-3018(24)00306-0. Epub 2025 Feb 12.
- Individual participant dataSharing planned: Yes. Individual participant data will be made available to researchers upon request. The IPD to be shared will be negotiated with the researchers
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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.
Maxensia Owor, MBChB, MMed, MPH study chair
MU-JHU CARE
Lisa Noguchi, PhD, CNM study chair
Johns Hopkins Bloomberg School of Public Health
Jen Balkus, PhD, MPH study chair
Hans Rosling Center for Population Health
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)-004 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 18 inclusion and 32 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 4 Aug 2023. 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 4 Aug 2023). 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 Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms (time frame: Measured through Month 3.5). The study lists 22 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 NCT04140266, which also lists 1 linked publication.
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 4 Aug 2023.