HIV-Target Cell Response in Women Initiating Various Contraceptive Methods in High HIV-Incidence Areas: Zim CHIC

Study Overview
=================
Brief Summary
-----------------
This study is being done to understand if using birth control causes changes in the immune cells within the reproductive tract of healthy women. Immune cells are important because they help prevent infections from starting and help fight infections that have started. Immune cells are also the type of cells that HIV (human immunodeficiency virus) infects so understanding more about them will help to better understand how to prevent the spread of HIV. Immune cells will be studied from the reproductive tract of women who want to start using one of the following contraceptives: Depo-Provera (DMPA), NET-EN, MPA/E2 (Cyclofem®), the levonorgestrel subdermal implant (Jadelle® ), the etonogestrel subdermal implant (Implanon® or Nexplanon® ) and the copper IUD.

Official Title
-----------------
HIV-Target Cell Response in Women Initiating Various Contraceptive Methods in High HIV-Incidence Areas: Zim CHIC

Conditions
-----------------
HIV, Contraception, Immune Cells (Mucosal and Systemic), Microbiota

Intervention / Treatment
-----------------
* Drug: DMPA
* Drug: NET-EN
* Drug: MPA/E2
* Device: LNG-I
* Device: ENG-I
* Device: Cu-IUD


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 through 34 years (inclusive) at screening Non-pregnant women in general good health as determined by the site clinician Premenopausal with history of regular menstrual cycles (regular cycles defined as occurring every 21-35 days when not using hormones and with a variation of typical cycle length of no more than 5 days) Able and willing to provide written informed consent to be screened for and to take part in the study. Including willingness to undergo all study-related assessments and follow all study-related procedures Able and willing to provide adequate locator information HIV-uninfected based on testing performed by study staff at screening At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products while enrolled in this trial Exclusion Criteria: Use of any hormonal or intrauterine contraceptive method within 30 days of enrollment Use of DMPA or NET-EN within 10 months of enrollment Pregnancy or breastfeeding within 60 days of enrollment Surgical procedure involving the pelvis in the 30 days prior to enrollment (includes dilation and curettage, cryosurgery and biopsy of the vagina, vulva, cervix, and endometrium) Internal vaginal use of any device (includes sex toys, cervical caps, diaphragms, menstrual collection devices, and pessaries; excludes tampons and condoms) or product (includes N9, microbicide, douche, antifungal, steroid, or hormone) in the 30 days prior to enrollment New sexual partner within 90 days of enrollment Urogenital infection or suspected infection within 30 days of enrollment including: symptomatic candidiasis, trichomoniasis, and symptomatic BV; or cervical infection, including N. gonorrhoeae, Chlamydia trachomatis, or mucopurulent cervicitis; syphilis; HSV lesions, or other sores (Note: seropositive HSV without active lesions will not be excluded); acute pelvic inflammatory disease; urinary tract infection; recent exposure to a partner with GC, CT, Trichomonas, syphilis, or NGU. Women who have had diagnosed genital infections should have completed treatment at least 30 days before the time of enrollment. Any history of immunosuppression (includes diabetes, HIV infection, and chronic steroid use) Antibiotic or antifungal therapy (vaginal or systemic) within 30 days of enrollment Menses or other vaginal bleeding at the time of Enrollment* (*Women who have vaginal bleeding at the scheduled Enrollment Visit may return at a different date to be re-examined and possibly enrolled provided they are still within the 90-day screening window and meet all criteria). Vaginal or anal intercourse within 2 days (48 hours) prior to enrollment Heterosexual intercourse since last menses that places the participant at risk of pregnancy (without condom use or sterilization of at least one partner) History of hysterectomy History of malignancy within the pelvis (includes uterus, cervix, vagina, and vulva) Contraindication, allergy or intolerance to use of the contraceptive desired by the participant Any condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DMPA<br>Depot medroxyprogesterone acetate | Drug: DMPA<br>* Depot medroxyprogesterone acetate<br>* Other names: Depot medroxyprogesterone acetate (DMPA);|
| NET-EN<br>Norethisterone enantate | Drug: NET-EN<br>* Norethisterone enantate<br>* Other names: Norethisterone enantate (NET-EN);|
| MPA/E2<br>Medroxyprogesterone acetate and estradiol cypionate | Drug: MPA/E2<br>* Medroxyprogesterone acetate and estradiol cypionate<br>* Other names: Medroxyprogesterone acetate and estradiol cypionate (MPA/E2);|
| LNG-I<br>Levonorgestrel subdermal implant | Device: LNG-I<br>* Levonorgestrel subdermal implant<br>* Other names: Levonorgestrel subdermal implant (LNG-I);|
| ENG-I<br>Etonogestrel subdermal implant | Device: ENG-I<br>* Etonogestrel subdermal implant<br>* Other names: Etonogestrel subdermal implant (ENG-I);|
| Cu-IUD<br>Copper IUD | Device: Cu-IUD<br>* Copper IUD<br>* Other names: Copper IUD (Cu-IUD);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genital tract CD4 cells (number and % expressing CCR5) | To quantify and characterize immune cell populations and HIV-tropic receptor expression in the genital tract and blood at baseline and after 1, 3 and 6 months of typical contraceptive use. Immune cell populations will be quantified and characterized using flow cytometry. | Change from baseline at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal microbiota (key microbes) | To describe the microflora of the genital tracts of healthy asymptomatic women before and after 1, 3 and 6 months of typical contraceptive use and to assess changes in the vaginal ecology within the first 6-months of contraceptive use. qPCR for key microflora and Nugent scores will be used. | Change from baseline at 3 months | 
| Serum hemoglobin | To objectively assess blood count before and at 1,3,and 6 months following initiation of each contraceptive method. Standard clinical complete blood count (CBC) will be obtained at each visit. | Change from baseline at 6 months | 
| Serum concentration of estradiol and progesterone/progestin | To assess relative serum concentrations of endogenous and exogenous sex hormones before and after contraceptive use. Hormonal concentrations will be assessed by measuring blood levels of estrogen and progesterone as well as blood levels of the contraceptive progestin corresponding to the cohort group for that participant. | Change from baseline at 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IUD, immune cells, contraception, intrauterine device, copper, microbiota, DMPA, etonogestrel, subdermal implant, NET-EN, Jadelle, Implanon, Cyclofem