Pharmacokinetic and Safety Study of a 90 Day Intravaginal Ring Containing Tenofovir

Inclusion Criteria

• Assigned female sex at birth
• Note: Participants who are female at birth, who now identify as male, will not be excluded so long as they are not on female-to-male transition therapy.
• Age 18 through 45 years (inclusive) at Screening, verified per site standard operating procedures (SOPs)
• Able and willing to provide written informed consent to be screened for and enrolled in MTN-038
• Able and willing to provide adequate locator information, as defined in site SOPs
• Able to communicate in spoken and written English
• Available for all visits and able and willing to comply with all study procedural requirements
• Willing to abstain from receptive vaginal or anal sexual activities for 72 hours prior to each clinical visit and for 72 hours after biopsy collection
• Willing to use male condoms for penile-vaginal and penile-rectal sexual intercourse for the duration of study participation
• Per participant report, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment, and intending to continue use of an effective method for the duration of study participation; effective methods include:
• hormonal methods (except contraceptive vaginal ring)
• intrauterine device (IUD)
• sterilization (of participant or partner, as defined in site SOPs)
• having sex exclusively with individuals assigned female sex at birth
• sexually abstinent as defined by abstaining from penile-vaginal intercourse for 90 days prior to Enrollment, and intending to remain abstinent for the duration of study participation
• In general good health as determined by the Investigator of Record (IoR)/designee at Screening and Enrollment
• HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithm in the study protocol)
• Per participant report at Screening, regular menstrual cycles with at least 21 days between menses
• Note: This criterion is not applicable to participants who report using a progestin-only method of contraception at Screening (e.g., Depo-Provera or levonorgestrel-releasing IUD) nor to participants using continuous combination oral contraceptive pills, as the absence of regular menstrual cycles is an expected, normal consequence in this context.
• Per participant report at Screening and Enrollment, states a willingness to refrain from inserting any non-study vaginal and rectal products or objects into the vagina or rectum including, but not limited to spermicides, female condoms, diaphragms, intravaginal rings, vaginal or rectal medications, menstrual cups, cervical caps, douches, lubricants, and sex toys (vibrators, dildos, etc.) for the 24 hours preceding the Enrollment Visit and for the duration of study participation.
• Note: Use of tampons is permitted except for 24 hours prior to clinic visits in which CVF samples are scheduled to be collected.
• Participants over the age of 21 (inclusive) must have documentation of a satisfactory Pap within the past 3 years prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result
• At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal or rectal products, or vaccines after the Screening Visit and for the duration of study participation

Exclusion Criteria

• Pregnant at Screening or Enrollment or plans to become pregnant during the study period
• Note: A documented negative pregnancy test performed by study staff is required for inclusion; however, a self-reported pregnancy is adequate for exclusion from the study.
• Diagnosed with symptomatic urinary tract infection (UTI) or reproductive tract infection (RTI) at Screening or Enrollment
• Otherwise eligible par