Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy

Inclusion Criteria

• Age 18 through 40 years (inclusive) at Enrollment, verified per site standard operating procedures (SOPs).
• At Enrollment, evidence of a viable, intrauterine, singleton pregnancy with sonographic confirmation, including for gestational age assessment.
• Note: If adequate (per judgment of Investigator of Record [IoR]/designee) sonographic results are not available from medical records at Screening, an ultrasound must be performed and results be available for review at Enrollment for all Cohorts. The ultrasound should be performed no later than the 36th week of gestation for Cohort 1 or the 28th week of gestation for Cohort 2.
• At Enrollment, pregnancy within gestational age limits of the currently enrolling cohort (per the study protocol).
• HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithm in the study protocol).
• At Screening and Enrollment, intending to continue her pregnancy until delivery.
• At Screening and Enrollment, intending to deliver at a health center or hospital where adequate records may be obtained, as defined in site SOPs.
• Note: Plans to deliver at a health center or hospital where adequate records may be obtained is inclusionary due to logistical challenges related to collection of vaginal rings (VRs), specimens and delivery outcome data outside of those settings.
• At Screening and Enrollment, willing to be randomized at time of enrollment to either of the two study arms, and to continue study product use until delivery.
• Able and willing to comply with all study requirements and complete all study procedures.
• Able and willing to provide the following:
• Informed consent for her and her infant to be screened for and to enroll in MTN-042, as defined in site SOPs.
• Adequate locator information, as defined in site SOPs.
• Adequate documentation of registration for antenatal care, as defined in site SOPs.
• Permission to contact participant's antenatal and postpartum care provider(s) and to obtain copies of antenatal and postpartum care records.
• At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation, unless approved by the Protocol Safety Review Team (PSRT).

Exclusion Criteria

• Per participant report at Screening and/or Enrollment, intends to do any of the following during the study participation period:
• Use oral pre-exposure prophylaxis (PrEP) outside the context of study participation.
• Relocate away from the study site.
• Travel away from the study site for a time period that would interfere with study participation.
• At Screening or Enrollment, has a positive HIV test.
• At Screening or Enrollment, diagnosed with urinary tract infection (UTI), cervicitis, sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring treatment per World Health Organization (WHO) guidelines.
• Note: Detection of bacterial vaginosis (BV) or candida in the absence of symptoms is not exclusionary. Otherwise eligible participants diagnosed during screening with a UTI, cervicitis, or STI/RTI requiring treatment per WHO guidelines are offered treatment consistent with WHO recommendations. If treatment is completed and symptoms have resolved within 35 days of obtaining informed consent for screening, the participant may be enrolled.
• At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.*
• Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the Investigator of Record (IoR)/designee is considered expected bleeding and is not exclusionary.
• Participant report, clinical evidence and/or antenatal/medical care record of any of the following:
• Currently breastfeeding at Enrollment.
• Known adverse reaction to any of the study products (ever).
• Known