Clinical trial NCT02762617 (phase 1, status: terminated)
Conditions: healthy, hiv
ICD codes: Z76.3, Z76.2, B20, Z71.7, O98.72, Z21, O98.73, R75, Z11.4
Drugs: tenofovir disoproxil fumarate intravaginal ring, placebo intravaginal ring (ivr)
SMILES: C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    safety-related
  
Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-45 years (inclusive) at screening.

          -  General good health (by volunteer history and per investigator discretion) without any
             clinically significant systemic disease (including, but not limited to significant
             liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease,
             osteoporosis or bone disease, and diabetes).

          -  Able and willing to provide written informed consent to be screened for and take part
             in the study.

          -  Able and willing to provide adequate locator information.

          -  Able and willing to avoid receptive vaginal and anal intercourse for 1 week after each
             biopsy.

          -  HIV-uninfected based on testing performed by study staff during screening procedures
             (per applicable algorithm in Appendix II).

          -  Using a copper IUD or any hormonal contraceptive method, other than an IVR, for a
             minimum of 2 months and intending to use the same method for the duration of study
             participation.

          -  Per participant report, sexually active, defined as having vaginal intercourse at
             least once in the month prior to screening.

          -  Have a regular sex partner and willing to have at least 4 sex acts per month for the
             duration of the study. Sex act is defined as penile-vaginal penetrative intercourse.
             Study staff will provide condoms to all study participants. Participants will not be
             restricted from engaging in oral sex.

          -  Has not used pre- or post-exposure prophylaxis for HIV exposure in the 3 months prior
             to Screening.

          -  Per participant report at Screening and Enrollment, agrees not to participate in other
             research studies involving drugs, medical devices, or vaginal products for the
             duration of study participation.

          -  At Screening, participant states she is able and willing to refrain from taking
             traditional herbs or medicines and is willing to refrain from inserting any non-study
             vaginal products or objects into the vagina, including but not limited to,
             spermicides, diaphragms, contraceptive vaginal rings, vaginal medications, vaginal
             probiotics/pre-biotics, menstrual cups, cervical caps (or any other vaginal barrier
             method), douches, lubricants, vaginal drying agents and sex toys (vibrators, dildos,
             etc.). Tampons may be used, but for menses only.

          -  Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to
             easy genital tract sample collection.

        Exclusion Criteria:

        Women must meet none of the following criteria prior to genital sampling at Enrollment:

        Participant report of any of the following at Screening:

          -  Sex in the past 3 months or any possibility of sex during study participation with a
             partner who is HIV+ or with a partner of unknown HIV status.

          -  Known adverse reaction to polyurethane or to any components of the study product or
             allergy to both silver nitrate and Monsel's solution.

          -  Active hepatitis B infection.

          -  Chronic, recurrent, and/or acute vulvar or vaginal symptoms (pain, irritation,
             spotting, etc.).

          -  Known bleeding disorder that could lead to prolonged or continuous bleeding with
             biopsy.

          -  Intending to become pregnant during the period of study participation.

          -  Currently breastfeeding or planning to breastfeed during the course of the study.

          -  Menopause.

          -  History of unexplained or unresolved intermenstrual bleeding in the 3 months prior to
             screening.

          -  History of gynecological procedures (including genital piercing) on the external
             genitalia, vagina or cervix in the last 14 days.

          -  Hysterectomy.

          -  Women using contraceptive IVRs because the study product is an IVR.

          -  Systemic use in the last 2 weeks or anticipated use during the study period of any of
             the following: corticosteroids, anticoagulants or ARVs.

          -  Plans to relocate away from the study site area during the period of study
             participation.

          -  Grade 1 or higher laboratory abnormality, as defined by the DAIDS Table for Grading
             the Severity of Adult and Pediatric AEs, Version 2.0, Nov 2014.

          -  At Screening or Enrollment, is pregnant (based on urine pregnancy test).

          -  In the last three months, diagnosed with or treated for any STI. Note: Women with a
             history of condylomata or genital herpes may be considered for eligibility as long as
             there are no lesions on exam. HSV 1 and 2 serologies will be obtained. Participants
             will be included regardless of the results of these serologies.

          -  Reproductive tract infection (RTI) or pelvic inflammatory disease (PID) requiring
             treatment per local guidelines in Kenya and Centers for Disease Control and Prevention
             (CDC) guidelines in the US at Screening or Enrollment.

        Note: Otherwise eligible women diagnosed with symptomatic vulvovaginal candidiasis (VVC),
        symptomatic bacterial vaginosis (BV) or urinary tract infection (UTI) will be eligible if
        Visit 2 (Enrollment) is scheduled after all symptoms have resolved and at least two weeks
        after completing treatment. Women with recurrent VVC and symptomatic BV despite treatment
        will be offered another course of treatment and will not be eligible.

          -  Positive test for Trichomonas vaginalis, Neisseria gonorrhea or Chlamydia trachomatis
             at screening.

          -  Positive test for hepatitis B (defined as positive for hepatitis B surface antigen).

          -  Reactive serologic test for syphilis at screening (per local guidelines). Note: Women
             with a history of syphilis that was not acquired and/or treated within the past 3
             months and that has been appropriately treated may be considered for eligibility.

          -  At Screening or Enrollment, has a clinically apparent Grade 1 or higher pelvic exam
             finding (observed by study clinician or designee) per the DAIDS Table for Grading the
             Severity of Adult and Pediatric AEs, Addendum 1, Female Genital Grading Table for Use
             in Microbicide Studies.

        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 PL/designee is considered expected non-menstrual bleeding and is not exclusionary.

        - Pap result Grade 2 or higher according to the Female Genital Grading Table for Use in
        Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric AEs,
        Version 1.0, December 2004 (Clarification dated August 2009).

        Note: Women 21 years of age or older with a documented normal result within the 12 months
        prior to enrollment need not have Pap smear during the screening period. Women with a Grade
        1 abnormal Pap smear can be enrolled upon completion of the initial phase of evaluation if
        no current treatment is indicated (based on local standard of care for management of
        abnormal cervical cytology). Need for a repeat Pap within 6 months does not preclude
        enrollment prior to that result becoming available.

          -  At Screening, has severe pelvic relaxation such that either the vaginal walls or the
             uterine cervix descend beyond the vaginal introitus with Valsalva maneuver.

          -  Has any condition that, in the investigator's opinion, would preclude informed
             consent, make study participation unsafe, complicate interpretation of study outcome
             data, or otherwise interfere with achieving the study objectives.