Evaluating the Safety of Tenofovir Vaginal Gel in HIV-Uninfected Pregnant Women

Inclusion Criteria:

• Age 18 through 45 years (inclusive) at screening, verified per site standard operating procedures (SOPs)
• At enrollment, singleton, viable pregnancy of gestational age within the limits for current group for enrollment
• Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening

• Able and willing to provide the following:

  • Written informed consent to be screened for and take part in the study
  • Adequate locator information, as defined in site SOPs
  • Adequate documentation of entry to antenatal care, as defined in site SOPs
  • Permission to contact and provision of adequate contact information for participant's antenatal care provider
  • Permission to obtain copies of antenatal care records More information on this criterion can be found in the protocol.
• HIV-uninfected based on testing performed by study staff at screening and enrollment (per algorithm in protocol)
• Per the clinical judgment of the Investigator of Record (IoR)/designee at enrollment, pelvic exam (including cervical exam) normal for estimated gestational age and parity
• Per the clinical judgment of the IoR/designee at enrollment, ultrasound results are complete, consistent with normal singleton intrauterine pregnancy, and provide an assessment of gestational age. More information on this criterion can be found in the protocol.
• Per participant mother report, willingness by the participant mother to receive information regarding and consider participation in MTN-016, a pregnancy registry study that collects additional information on pregnancy safety and the growth and development of babies up to 1 year of age
• At screening and enrollment, agrees not to participate in other research studies involving drugs, vaccines, medical devices, or vaginal products for the duration of study participation

Exclusion Criteria:

• Participant mother reported any of the following:

  • Prior exposure to gel or oral formulation of tenofovir (ever)
  • Known sensitivity to any component of the study products (ever)
  • Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to enrollment
  • Participation in any research study involving drugs, medical devices, or vaginal products during the current pregnancy
  • Non-therapeutic injection drug use in the 12 months prior to screening

• By participant mother report, noted on antenatal record, or clinical evidence at the time of enrollment of any of the following in the current pregnancy:

  • Multiple gestation
  • Placenta previa
  • Cervical cerclage
  • Abnormal fetal anatomy (in the opinion of the IoR or designee)
  • Intrauterine growth restriction
  • Pre-existing or gestational diabetes
  • Hypertensive disorder of pregnancy
  • Treatment for preterm labor

• By participant mother report, or noted on review of medical record, any of the following in a previous pregnancy:

  • Intrauterine growth restriction
  • Gestational diabetes
  • Hypertensive disorder of pregnancy
  • Intrauterine fetal demise (estimated gestational age 20 weeks or greater)
  • Delivery prior to 37 0/7 weeks

• By participant mother report at screening or enrollment:

  • Intends to relocate away from the study site during the period of expected study visits
  • Plans to travel away from the study site during the expected study product dosing period, such that travel would preclude the completion of one or more scheduled study visits
  • Plans to deliver outside of a hospital. More information on this criterion can be found in the protocol.
• Currently breastfeeding
• 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, including active tuberculosis, or medication use that would make study participation unsafe. More information on this criterion can be found in the protocol.
• At enrollment, clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff). More information on this criterion can be found in the protocol.

• Has any of the following laboratory abnormalities during the screening period:

  • Hemoglobin value of Grade 3 or higher according to Division of AIDS (DAIDS) Toxicity Table
  • Platelet count less than 100,000 mm^3
  • Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 1.5 times the upper limit of normal
  • Serum creatinine greater than 1.0 mg/dL
  • Hepatitis B surface antigen (HBsAg) positivity
  • Urine dipstick positive for protein greater than or equal to 2
  • Urine dipstick positive for glucose greater than or equal to 2
  • Positive for malaria (at sites with capacity, where women are at risk and testing through antenatal care provider is not otherwise available)
  • More information on this criterion can be found in the protocol
• Grade 2 or higher Pap result (e.g., high-grade squamous intraepithelial lesion). More information on this criterion can be found in the protocol.
• Diagnosed with a sexually transmitted infection or reproductive tract infection requiring treatment, per current Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO) guidelines, as applicable. More information on this criterion can be found in the protocol.
• 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