MATRIX-002: Trial to Assess Acceptability and Safety of Two Placebo Vaginal Films

Inclusion Criteria:

• Assigned female sex at birth.

• Able and willing to provide written informed consent to be screened for and enrolledin MATRIX-002 in one of the study languages.

• Able and willing to provide adequate contact/locator information.

• Able and willing to comply with all protocol requirements, including:

• Abstaining from all receptive sexual intercourse (vaginal, anal, digital, oral)for the first month of product use.

• Abstaining from using other intravaginal products for the first month ofproduct use.

• Abstaining from engaging in intravaginal practices for the first month ofproduct use.

• Refraining from participation in other research studies for the duration of thestudy unless approved by the Protocol Safety Review Team.

• Responding to scheduled phone/short message service contacts.

• Attending all clinic follow-up visits.

• HIV-uninfected based on testing performed at Screening and Enrollment.

• Per participant report, if in a relationship, must be in a mutually monogamousrelationship with a partner who is not known to be HIV positive or to currently havea sexually transmitted infection.

• Negative urine pregnancy test at Screening and Enrollment.

• Participants over the age of 21 (inclusive) must have documentation of a Grade 0 Papsmear within the past 3 years prior to Enrollment, or a Grade 1 Pap smear atScreening with no treatment required, per the Female Genital Grading Table for Usein Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table forGrading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.

• Protected from pregnancy starting two weeks before Screening and continuing for theduration of study participation by an effective contraceptive method; effectivemethods include:

• Hormonal methods except vaginal rings

• Copper intrauterine device

• Sterilization of participant

• Correct and consistent condom use (for US site only)

• Abstinence from penile-vaginal intercourse

Inclusion Criteria for Sexual Partners:

• Identifies as a sexual partner of a MATRIX-002 participant.

• Identified by participant as a sexual partner during MATRIX-002 for whom theparticipant has given permission to contact.

• Able and willing to provide written informed consent in one of the study languages.

• Able and willing to complete the required study procedures.

• Must be 18 years old or above at the time of their study participation.

Exclusion Criteria:

• Per participant report at Screening and Enrollment, intends to do any of thefollowing during the study participation period:

• Become pregnant.

• Breastfeed.

• Relocate away from the study site.

• Travel away from the study site for a time period that would interfere withproduct resupply and/or study participation.

• Positive HIV test at Screening or Enrollment.

• Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis,or Treponema pallidum (Syphilis) at Screening or (per participant report) treatedfor potential sexually transmitted infection within past 12 months.

• Diagnosed with urinary tract infection, pelvic inflammatory disease, or reproductivetract infection requiring treatment per WHO guidelines at Enrollment.

• Clinically apparent Grade 2 or higher pelvic exam finding per the DAIDS Table forGrading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/orAddenda 1 (Female Genital Grading Table for Use in Microbicide Studies [DatedNovember 2007]) at Enrollment.

• Participant report and/or clinical evidence of any of the following:

• Known adverse reaction to any of the study product materials (ever).

• Hysterectomy.

• Surgical procedure involving the pelvis in the 30 days prior to Enrollment.

• Use of diaphragm, NuvaRing, or (for African sites only) spermicide forcontraception in the two weeks prior to Screening.

• Antibiotic or antifungal (oral or intravaginal) therapy within 7 days ofEnrollment.

• Prior use of post-exposure prophylaxis or oral pre-exposure prophylaxis (including emtricitabine/disoproxil fumarate) in the 4 weeks prior to Screeningor any prior use of long-acting systemic pre-exposure prophylaxis (includingcabotegravir or islatravir).

• Use of any of the following in the 12 months prior to Screening: stimulants (cocaine [including crack], methamphetamine, or non-physician prescribedpharmaceutical-grade stimulants), or inhaled nitrates, or illicit injectiondrug use of any kind.

• At Screening or Enrollment, as determined by the Investigator ofRecord/designee, has any significant uncontrolled active or chroniccardiovascular, renal, liver, hematologic, neurologic, gastrointestinal,psychiatric, endocrine, respiratory, immunologic disorder or infectiousdisease.

• Has any of the following laboratory abnormalities at Screening:

• Grade 2 or higher Aspartate aminotransferase, alanine transaminase, creatinine,or Hemoglobin per the DAIDS Table for Grading Adult and Pediatric AdverseEvents, Corrected Version 2.1, July 2017.

• Has any other condition that, in the opinion of the Investigator of record/designee,would preclude informed consent, make study participation unsafe, complicateinterpretation of study outcome data, or otherwise interfere with achieving thestudy objectives.