HIV Infections
Conditions
Brief 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.
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.
Interventions
DRUGDapivirine (DPV) Vaginal Ring (VR)-004
Vaginal ring containing 25 mg of DPV
DRUGTruvada Tablet
Oral tablet containing 200 mg emtricitabine (FTC)/300 mg tenofovir disoproxil fumarate (TDF)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria - Mother 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. * 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. Inclusion Criteria - Infant 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean of Infant TFV-DP Concentrations by Visit | 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. |
| Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | 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 | 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 | 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 | 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. |
| Number of Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual Drug Levels in Returned VRs | Measured through Month 3.5 | The residual DPV concentrations from the returned VRs are summarized. |
| Participant Willingness to Use Their Assigned Study Products During Breastfeeding in the Future (Y/N) | Measured through Month 3.5 | Based on participant report to the question Would you be willing to use the study product for HIV prevention while breastfeeding in the future? |
| Proportion of Participants Who Find Their Study Product to be at Least as Acceptable as Other HIV Prevention Methods | Measured through Month 3.5 | 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. |
| The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Measured through Month 3 | 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. |
Countries
Malawi, South Africa, Uganda, Zimbabwe
Participant flow
Recruitment details
197 mother-infant pairs were enrolled in 4 African countries from September 2020 until July 2021.
Pre-assignment details
197 mother-infant pairs were enrolled in the study. When the mothers are enrolled and discontinued from the study, their infants are enrolled or discontinued.
Participants by arm
| Arm | Count |
|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 Adverse Events for Mothers randomized to the DPV VR study arm. | 148 |
| Mothers - Group B: Truvada Tablet Adverse Events for Mothers randomized to the Truvada oral tablet study arm. | 49 |
| Infants - Group A: DPV VR Adverse Events for Infants of Mothers randomized to the DPV VR study arm. | 148 |
| Infants - Group B: Truvada Tablet Adverse Events for Infants of Mothers randomized to the Truvada oral tablet study arm. | 49 |
| Total | 394 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Total | Infants - Group A: DPV VR | Infants - Group B: Truvada Tablet | Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Mothers - Group B: Truvada Tablet |
|---|---|---|---|---|---|
| Age, Continuous Infants' Age, weeks | 9 weeks | 9 weeks | 8 weeks | — | — |
| Age, Continuous Mothers' Age, years | 26 years | — | — | 26 years | 25 years |
| Age, Customized Infant age 6 to 9 weeks | 121 Participants | 87 Participants | 34 Participants | 0 Participants | 0 Participants |
| Age, Customized Infant age >9 weeks to 12 weeks | 76 Participants | 61 Participants | 15 Participants | 0 Participants | 0 Participants |
| Age, Customized mother age 18-19 years | 19 Participants | 0 Participants | 0 Participants | 14 Participants | 5 Participants |
| Age, Customized mother age 20-24 years | 67 Participants | 0 Participants | 0 Participants | 50 Participants | 17 Participants |
| Age, Customized mother age 25-29 years | 54 Participants | 0 Participants | 0 Participants | 42 Participants | 12 Participants |
| Age, Customized mother age 30-34 years | 40 Participants | 0 Participants | 0 Participants | 28 Participants | 12 Participants |
| Age, Customized mother age 35-39 years | 16 Participants | 0 Participants | 0 Participants | 13 Participants | 3 Participants |
| Age, Customized mother age 40-45 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 394 Participants | 148 Participants | 49 Participants | 148 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 394 Participants | 148 Participants | 49 Participants | 148 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Malawi | 78 participants | 29 participants | 10 participants | 29 participants | 10 participants |
| Region of Enrollment South Africa | 72 participants | 27 participants | 9 participants | 27 participants | 9 participants |
| Region of Enrollment Uganda | 110 participants | 42 participants | 13 participants | 42 participants | 13 participants |
| Region of Enrollment Zimbabwe | 134 participants | 50 participants | 17 participants | 50 participants | 17 participants |
| Sex: Female, Male Female | 305 Participants | 84 Participants | 24 Participants | 148 Participants | 49 Participants |
| Sex: Female, Male Male | 89 Participants | 64 Participants | 25 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 148 | 0 / 49 | 0 / 148 | 0 / 49 |
| other Total, other adverse events | 92 / 148 | 35 / 49 | 112 / 148 | 32 / 49 |
| serious Total, serious adverse events | 2 / 148 | 0 / 49 | 4 / 148 | 0 / 49 |
Outcome results
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the DPV VR arm with available and evaluable plasma specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant DPV Concentrations From Plasma by Visit | Week 2 | 11.7 pg/mL | Geometric Coefficient of Variation 46.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant DPV Concentrations From Plasma by Visit | Month 1 | 11.5 pg/mL | Geometric Coefficient of Variation 35.7 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant DPV Concentrations From Plasma by Visit | Month 2 | 11.0 pg/mL | Geometric Coefficient of Variation 31.7 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant DPV Concentrations From Plasma by Visit | Product Use End Visit | 10.5 pg/mL | Geometric Coefficient of Variation 19.8 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant DPV Concentrations From Plasma by Visit | Study End Visit | 10 pg/mL | Geometric Coefficient of Variation 0 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant FTC-TP Concentration by Visit | Week 2 | 0.1 pmol/punch | Geometric Coefficient of Variation 23.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant FTC-TP Concentration by Visit | Month 1 | 0.1 pmol/punch | Geometric Coefficient of Variation 16.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant FTC-TP Concentration by Visit | Month 2 | 0.1 pmol/punch | Geometric Coefficient of Variation 15.4 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant FTC-TP Concentration by Visit | Product Use End Visit | 0.1 pmol/punch | Geometric Coefficient of Variation 12.1 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant FTC-TP Concentration by Visit | Study End Visit | 0.1 pmol/punch | Geometric Coefficient of Variation 0 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant TFV-DP Concentrations by Visit | Week 2 | 15.6 fmol/punch | Geometric Coefficient of Variation 0 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant TFV-DP Concentrations by Visit | Month 1 | 15.6 fmol/punch | Geometric Coefficient of Variation 0 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant TFV-DP Concentrations by Visit | Month 2 | 15.6 fmol/punch | Geometric Coefficient of Variation 0 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant TFV-DP Concentrations by Visit | Product Use End Visit | 15.6 fmol/punch | Geometric Coefficient of Variation 0 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Infant TFV-DP Concentrations by Visit | Study End Visit | 15.6 fmol/punch | Geometric Coefficient of Variation 0 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the DPV VR arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Product Use End Visit | 402.8 pg/mL | Geometric Coefficient of Variation 154.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Week 1 | 529.4 pg/mL | Geometric Coefficient of Variation 108 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Week 2 | 492.0 pg/mL | Geometric Coefficient of Variation 122.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Month 1 | 457.0 pg/mL | Geometric Coefficient of Variation 119.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Month 2 | 418.9 pg/mL | Geometric Coefficient of Variation 545 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Breastmilk by Visit | Study End Visit | 20.0 pg/mL | Geometric Coefficient of Variation 210.7 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the DPV VR arm with available and evaluable plasma specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Week 1 | 327.9 pg/mL | Geometric Coefficient of Variation 61.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Week 2 | 314.9 pg/mL | Geometric Coefficient of Variation 92.1 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Month 1 | 275.4 pg/mL | Geometric Coefficient of Variation 76.9 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Month 2 | 263.8 pg/mL | Geometric Coefficient of Variation 111.9 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Product Use End Visit | 260.4 pg/mL | Geometric Coefficient of Variation 87.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal DPV Concentrations From Plasma by Visit | Study End Visit | 16.7 pg/mL | Geometric Coefficient of Variation 93.5 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Week 1 | 552.6 mg/mL | Geometric Coefficient of Variation 167.4 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Week 2 | 447.6 mg/mL | Geometric Coefficient of Variation 329 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Month 1 | 319.9 mg/mL | Geometric Coefficient of Variation 453.8 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Month 2 | 313.0 mg/mL | Geometric Coefficient of Variation 707.9 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Product Use End Visit | 296.6 mg/mL | Geometric Coefficient of Variation 1099.2 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC Concentrations From Breastmilk by Visit | Study End Visit | 2.8 mg/mL | Geometric Coefficient of Variation 88.9 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Week 1 | 0.3 pmol/punch | Geometric Coefficient of Variation 51.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Week 2 | 0.3 pmol/punch | Geometric Coefficient of Variation 58.4 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Month 1 | 0.3 pmol/punch | Geometric Coefficient of Variation 91.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Month 2 | 0.2 pmol/punch | Geometric Coefficient of Variation 90.9 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Product Use End Visit | 0.2 pmol/punch | Geometric Coefficient of Variation 91.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal FTC-TP Concentrations by Visit | Study End Visit | 0.1 pmol/punch | Geometric Coefficient of Variation 21.9 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Week 2 | 4.3 ng/mL | Geometric Coefficient of Variation 89.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Week 1 | 5.6 ng/mL | Geometric Coefficient of Variation 72.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Month 1 | 3.3 ng/mL | Geometric Coefficient of Variation 108.3 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Month 2 | 3.2 ng/mL | Geometric Coefficient of Variation 120 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Product Use End Visit | 2.7 ng/mL | Geometric Coefficient of Variation 107.2 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV Concentrations From Breastmilk by Visit | Study End Visit | 0.6 ng/mL | Geometric Coefficient of Variation 106.5 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Week 1 | 254.6 fmol/punch | Geometric Coefficient of Variation 62.8 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Week 2 | 424.2 fmol/punch | Geometric Coefficient of Variation 65.2 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Month 1 | 524.7 fmol/punch | Geometric Coefficient of Variation 117.8 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Month 2 | 551.9 fmol/punch | Geometric Coefficient of Variation 97.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Product Use End Visit | 591.5 fmol/punch | Geometric Coefficient of Variation 135.5 |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Geometric Mean of Maternal TFV-DP Concentrations by Visit | Study End Visit | 330.8 fmol/punch | Geometric Coefficient of Variation 137.8 |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable FTC-TP Concentrations | Week 2 | 4 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable FTC-TP Concentrations | Month 1 | 2 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable FTC-TP Concentrations | Month 2 | 2 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable FTC-TP Concentrations | Product Use End Visit | 1 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable FTC-TP Concentrations | Study Exit Visit | 0 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the DPV VR arm with available and evaluable plasma specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable Plasma DPV Concentrations | Week 2 | 21 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable Plasma DPV Concentrations | Month 1 | 20 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable Plasma DPV Concentrations | Month 2 | 14 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable Plasma DPV Concentrations | Product Use End Visit | 7 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable Plasma DPV Concentrations | Study Exit Visit | 0 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the infants of mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes infants with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Mother results are in a separate section above.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable TFV-DP Concentrations | Week 2 | 0 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable TFV-DP Concentrations | Month 1 | 0 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable TFV-DP Concentrations | Month 2 | 0 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable TFV-DP Concentrations | Product Use End Visit | 0 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Infants With Detectable TFV-DP Concentrations | Study Exit Visit | 0 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the DPV VR arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infants are not included in this population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Week 1 | 137 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Week 2 | 137 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Month 1 | 138 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Month 2 | 138 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Product Use End Visit | 135 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk DPV Concentrations | Study End Visit | 94 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infants are not included in this population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Week 2 | 45 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Month 1 | 44 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Month 2 | 39 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Product Use End Visit | 40 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Week 1 | 47 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk FTC Concentrations | Study End Visit | 1 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable breastmilk specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infants are not included in this population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Week 1 | 47 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Week 2 | 44 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Month 1 | 42 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Month 2 | 38 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Product Use End Visit | 38 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Breastmilk TFV Concentrations | Study End Visit | 3 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Week 1 | 45 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Week 2 | 46 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Month 1 | 38 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Month 2 | 34 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Product Use End Visit | 38 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Emtricitabine Triphosphate (FTC-TP) Concentrations | Study End Visit | 1 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the DPV VR arm with available and evaluable plasma specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Week 1 | 139 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Week 2 | 136 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Month 1 | 139 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Month 2 | 138 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Product Use End Visit | 136 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Plasma Dapivirine (DPV) Concentrations | Study End Visit | 48 Participants |
Primary
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.
Time frame: Measured through Month 3.5
Population: This endpoint includes the mothers randomized to the Truvada arm with available and evaluable DBS specimens at the specific timepoint. The Overall Number of Participants Analyzed includes mothers with an evaluable specimen for at least one timepoint. Evaluable is defined as the specimens that were successfully tested at the central laboratory. Infant results are in a separate section below.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Week 1 | 47 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Week 2 | 48 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Month 1 | 45 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Month 2 | 44 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Product Use End Visit | 47 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number and Proportion of Mothers With Detectable Tenofovir Diphosphate (TFV-DP) Concentrations | Study End Visit | 45 Participants |
Primary
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
Time frame: Measured through Month 3.5
Population: Infants were exposed to study product through breastmilk. All enrolled mothers received study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number of Infant Participants With Grade 3 or Higher AEs in Both Study Arms | 10 Participants |
| Mothers - Group B: Truvada Tablet | Number of Infant Participants With Grade 3 or Higher AEs in Both Study Arms | 1 Participants |
Primary
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)
Time frame: Measured through Month 3.5
Population: All infants were exposed to study product through mothers' breastmilk. All enrolled mothers received study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number of Infant Participants With SAEs Including Infant Deaths in Both Study Arms | 4 Participants |
| Mothers - Group B: Truvada Tablet | Number of Infant Participants With SAEs Including Infant Deaths in Both Study Arms | 0 Participants |
Primary
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 \[Dated November 2007\])
Time frame: Measured through Month 3.5
Population: All enrolled mothers received study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number of Mother Participants With Grade 3 or Higher Adverse Events (AEs) in Both Study Arms | 3 Participants |
| Mothers - Group B: Truvada Tablet | Number of Mother Participants With Grade 3 or Higher Adverse Events (AEs) in Both Study Arms | 2 Participants |
Primary
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)
Time frame: Measured through Month 3.5
Population: All Mothers received study product and are used in the analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Number of Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms | 2 Participants |
| Mothers - Group B: Truvada Tablet | Number of Mother Participants With Serious Adverse Events (SAEs) Including Maternal Deaths in Both Study Arms | 0 Participants |
Secondary
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?
Time frame: Measured through Month 3.5
Population: The number of mothers analyzed includes all mothers who completed the Product End Use Visit Behavioral Assessment and responded to the willingness question. The count of participants who are willing, responded Yes to the question.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Participant Willingness to Use Their Assigned Study Products During Breastfeeding in the Future (Y/N) | 142 Participants |
| Mothers - Group B: Truvada Tablet | Participant Willingness to Use Their Assigned Study Products During Breastfeeding in the Future (Y/N) | 48 Participants |
Secondary
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.
Time frame: Measured through Month 3.5
Population: The number of mothers analyzed included those who completed the Product End Use Visit Behavioral Assessment and responded to the acceptability question. The mothers who answered Like very much or Like are included in the total who find the study product acceptable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Proportion of Participants Who Find Their Study Product to be at Least as Acceptable as Other HIV Prevention Methods | 141 Participants |
| Mothers - Group B: Truvada Tablet | Proportion of Participants Who Find Their Study Product to be at Least as Acceptable as Other HIV Prevention Methods | 46 Participants |
Secondary
Residual Drug Levels in Returned VRs
The residual DPV concentrations from the returned VRs are summarized.
Time frame: Measured through Month 3.5
Population: The analysis population includes mothers with evaluable residual DPV concentrations from returned vaginal rings (VRs). Rings returned on or after the Month 3 visit are included in the Month 3 summary.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Residual Drug Levels in Returned VRs | Month 1 | 22.1 mg |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Residual Drug Levels in Returned VRs | Month 2 | 22.4 mg |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | Residual Drug Levels in Returned VRs | Month 3 | 22.1 mg |
Secondary
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.
Time frame: Measured through Month 3
Population: Only mother participants are included in this endpoint since infants did not directly use study product. The number of mothers analyzed includes mother participants with a returned/used vaginal ring that was successfully analyzed for residual drug concentration (evaluable) for Group A (DPV VR) and only those participants with an available and evaluable dried blood plot specimen for mothers in Group B (Truvada). Rings returned after the Month 3 Product Use End Visit (PUEV) are excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 1 | 14 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 2 | 28 Participants |
| Mothers - Group A: Dapivirine (DPV) Vaginal Ring (VR)-004 | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 3 | 29 Participants |
| Mothers - Group B: Truvada Tablet | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 1 | 2 Participants |
| Mothers - Group B: Truvada Tablet | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 2 | 0 Participants |
| Mothers - Group B: Truvada Tablet | The Number of Mothers Non-adherent to Study Product for Each Month of Product Use by Study Product | Month 3 | 0 Participants |