HIV/AIDS Pregnancy and Childbirth Fertility-female
Conditions
Interventions
Tenofovir disoproxil fumarate and Levonorgestrel
Tenofovir
Placebo
Sponsors
United States Centers for Disease Control and Prevention
Eligibility
Sex/Gender
Female
Inclusion 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 (Visit 0) HIV risk score =4 (on HIV risk assessment tool developed for women in sub-Saharan Africa (included in Appendix II) • 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 at Visit 1 o Women with an abnormal VILI will be linked directly to cervical cancer screening through Papanicolaou smear testing and will not be eligible for enrollment unless cervical cancer screening is negative • 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 CM collection, as possible, and 48 hours before Visits 4 and 7 • 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: o Oral contraceptives (combined or progestin-only), contraceptive patch or contraceptive vaginal ring at least two (2) months prior to Visit 1 o Last DMPA injection received at least four (4) months prior to Visit 1 and has resumed re
Exclusion criteria
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. Note: If recently pregnant, must have had at least two spontaneous menses since 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 (detailed in Appendix VI and the standard operating procedures (SOP) manual, which is consistent with WHO guidelines http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf?ua=1 • In the last three (3) months, diagnosed with or treated for any STI or pelvic inflammatory disease o Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least six (6) months may be considered for eligibility if pelvic exam shows no vesicles or open lesions. • Positive test for HIV-1 (in accordance with national testing algorithm, Appendix IV), syphilis, Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) or HBsAg o NOTE: Women who test positive for HIV-1, syphilis, TV, GC, or CT will be treated for the STI at no cost at the CRC according to the 2015 Kenya National AIDS and STI Control Programme Algorithms for Managing Common STI Syndromes (https://aidsfree.usaid.gov/sites/default/files/hts_policy_kenya_2015.pdf); they will also receive face-to-face counseling, but will not be eligible to take part in the study. • Nugent score greater than or equal to 7 or a symptomatic BV clinical diagnosis as defined by Amsel’s criteria o Must have 3 of the 4 signs for a diagnosis of BV using Amsel’s criteria ? Discharge, white & homogeneous ? Elevated pH, >4.5 ? Amine odor present ? 20% clue cells present on wet mount • Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate genital and systemic safety of the TFV/LNG and TFV IVRs compared to the placebo during and after 90-days of use among women in Western Kenya | — |
Secondary
| Measure | Time frame |
|---|---|
| • Pharmacokinetics (PK) and pharmacodynamics (PD) of the IVR active pharmaceutical agents o To evaluate PK of TFV o To evaluate PK of LNG o To evaluate PD surrogate markers of contraceptive efficacy of LNG o To evaluate PD surrogate markers of microbicidal efficacy of TFV • To assess biological (microbiological/immunological) effects of IVRs on the female genital tract • To assess subjective and objective measures of tolerability • To assess subjective and objective measures of adherence • To assess acceptability (through quantitative data collection methods | — |
Countries
Kenya
Contacts
Public ContactBeatrice Nyagol
Study Clinician
Outcome results
None listed