PK/PD of Single Dose Dapivirine Vaginal Film

Inclusion criteria

• 18 years of age or older with a history of receptive vaginal intercourse.
• HIV negative by EIA within 28 days of enrollment.
• Understand and agree to local STI reporting requirements.
• Able and willing to provide written informed consent to take part in the study.
• Able and willing to provide adequate information for locator purposes.
• Availability to return for all study visits, barring unforeseen circumstances.
• Availability to return for the second formulation dosing at the same time in the subject's menstrual cycle as when the first formulation was administered, at least 10 days before menses.
• Willing to abstain from vaginal intercourse and insertion of anything (e.g., drug, vaginal douche, or sex toy) in vagina for 72 hours before each study product exposure, and 7 days following each vaginal sampling procedure.
• Willingness to have partner(s) use condoms (must not contain Nonoxynol-9) for the duration of the study.
• Agree not to participate in other research studies involving drugs and/or medical devices.
• Negative qualitative urine pregnancy test.
• Per participant report, using an effective method of contraception at enrollment; hormonal method (except vaginal ring) used continuously for the past 30 days; intrauterine device (IUD [copper or hormonal] inserted at least 30 days prior to enrollment); female sterilization; abstinent from sexual activity with male partner for the past 30 days; or sexual activity with vasectomized partner; and willingness to use effective method of contraception until the completion of final scheduled study visit if enrolled.
• Willingness to remain in the research unit for up to 24 hours on each of two dosing days, -

Exclusion criteria

• Current sexual partner known by participant to be HIV seropositive.
• Individuals who, by history, engage in condom-less intercourse with HIV-infected partners, or partners that have unknown HIV serostatus, or women who exchange sex for money, shelter, or gifts.
• Active sexually transmitted infection or documented treatment of sexually transmitted infections including, but not limited to: chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or PID within 6 months prior to enrollment.
• Known history of genital HSV (diagnosed by either clinical or laboratory test).
• Symptomatic vaginal candidiasis or bacterial vaginosis.
• Undiagnosed irregular uterine bleeding
• Pathology of the female genital tract, which in the judgment of the investigator might increase the risk of the study to the research participant.
• Individuals who are status post hysterectomy.
• History of any cervicovaginal procedure (i.e. colposcopy with cervical biopsy) within the past 2 months. Individuals who have a history of cone biopsy or extensive loop electrosurgical excision procedure (LEEP), which in the judgment of the investigator may affect permeability assessment.
• Any known primary or secondary uro-genital malformations, which in the assessment of the investigator may interfere with the intended urine collection for PK studies.
• Use of vaginally administered medications within 4 week of enrollment
• Any active urinary tract infection
• By history, subjects with irregular menstrual cycles.
• At screening:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 X the site laboratory ULN (upper limit of normal)
• Hemoglobin less than 10.0 g/dL
• Platelet count less than 100,000/mm3
• Other safety tests outside of the normal range that in the judgment of the investigator may interfere with conduct of the study.
• Positive findings on urinalysis that are clinically significant in the opinion of the investigator
• Estimated creatinine clearance < 60 ml/min based on established nomograms
• Recent history (past 6 months) of injection drug use or, a level of alcohol use that, in the judgement of the Investigator of Record, may interfere with the conduct of this study.
• Unwillingness to refrain from aspirin and NSAIDs product use for one week prior to and one week post study procedures.
• Use of warfarin or heparin.
• Use of systemic immunomodulatory medications within 4 weeks of enrollment.
• Use of product containing nonoxynol-9 within 4 weeks of enrollment.
• Use of any investigational products within 4 weeks of enrollment.
• Any other medical conditions deemed not safe for participation by the investigator.
• Any individual that is actively breast feeding.
• Post-menopausal defined as 12 months of amenorrhea.

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