Clinical trial: Tenofovir/Levonorgestrel Intravaginal Ring and Tenofovir Intravaginal Ring (NCT03762382)

Eligibility criteria:
Inclusion Criteria:

          -  Female, aged 18-34 years, inclusive

          -  General good health (by history and per clinician 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), uterus, and cervix

          -  Not pregnant or planning to become pregnant

          -  Pre-screening HIV risk score ≤4

          -  Currently having regular menstrual cycles (approximately 24-35 days) OR with a history
             of having regular menstrual cycles before contraceptive use, by report, and resumed
             some menstruation or spotting (with biochemical confirmation of ovulation)

          -  Willing to undergo Visual Inspection with Lugol's Iodine (VILI) for cervical
             abnormalities during pelvic exam

          -  Willing to abstain from use of vaginal products other than the study product,
             including tampons (except for during menses) , menstrual cups, vaginally inserted
             cloths or other materials, spermicides, lubricants, and douches for the whole study

          -  Willing to abstain from any vaginal intercourse starting 48 hours before certain study
             visits

          -  Vaginal and cervical anatomy that, in the opinion of the clinician, lends itself to
             easy genital tract sample collection and is absent of vesicles and ulcers

          -  No use of hormonal contraceptives within the following periods specified for each type
             of contraception method:

               -  Oral contraceptives (combined or progestin-only), contraceptive patch or
                  contraceptive vaginal ring in at least two (2) months

               -  Last DMPA injection received at least four (4) months ago and has resumed regular
                  menstruation

               -  Hormonal IUD/IUS removed at least four (4) months ago and has resumed regular
                  menstruation

               -  Hormonal implant removed at least six (6) months ago and has resumed regular
                  menstruation

          -  Willing to refrain from using any hormonal contraceptives for the entire study and to
             use only study-provided non-spermicidal male condoms with or without a study-provided
             Cu-IUD

          -  P4 ≥3.0 ng/ml

          -  Estimated glomerular filtration rate (eGFR) ≥90ml/min/1.73m2

          -  Willing to give voluntary consent and sign/mark an informed consent form

          -  Willing and able to comply with protocol requirements

        Exclusion Criteria:

          -  Body mass index (BMI) ≥30 kg/m

          -  History of hysterectomy

          -  Currently pregnant or within less than three (3) calendar months of the last pregnancy
             outcome.

          -  Currently breastfeeding or having breastfed an infant in the last two (2) months, or
             planning to breastfeed during the course of the study

          -  Contraindication to any study products-LNG, TFV, or excipient ingredients

          -  Contraindication to LNG

          -  In the last three (3) months, diagnosed with or treated for any STI or pelvic
             inflammatory disease

          -  Positive test for HIV-1, syphilis, Trichomonas vaginalis (TV), Neisseria gonorrhea
             (GC), Chlamydia trachomatis (CT) or HBsAg

          -  Nugent score greater than or equal to 7 or a symptomatic BV clinical diagnosis as
             defined by Amsel's criteria

          -  Suspected breast cancer or other progestin-sensitive cancer

          -  Suspected hepatic disease, including cirrhosis or viral hepatitis

          -  History of bleeding or coagulation problems

          -  Known current drug or alcohol abuse which could impact study compliance

          -  Grade 2 or higher laboratory abnormality, per the Division of AIDS, National Institute
             of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse
             Events, or clinically significant laboratory abnormality as determined by the
             clinician

          -  Use of any concomitant medications

          -  Participation in any other investigational trial with use of a drug/device within the
             last 30 days or planned participation in any other investigational trial with use of a
             drug/device during the study

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

          -  Labial elongation (due to pulling practices and use of botanicals or caustic agents)

          -  Abnormal finding on laboratory or physical examination or a social or medical
             condition in the volunteer which, in the opinion of the site co-PI(s), would make
             participation in the study unsafe or would complicate interpretation of data

          -  Currently using, or has used within the preceding one (1) month,
             emtricitabine/tenofovir disoproxil fumarate (TDF/FTC or Truvada®) or any other
             tenofovir product, and/or has plans to use a non-study tenofovir product in any form
             during the study
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 34 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? 0