Impact of Hormonal Contraception on HIV Acquisition and Transmission Risk

Study Overview
=================
Brief Summary
-----------------
This is a prospective cohort study focusing on HIV negative women. The investigators want to learn how the contraceptive methods of depot medroxyprogesterone acetate (DMPA), etonogestrel implant (Eng-Implant), levonorgestrel intrauterine device (Lng-IUD) and the ParaGard® T 380A Intrauterine Copper Contraceptive impact the vaginal immune environment.

Detailed Description
-----------------
The three proposed aims will evaluate the effect of four contraceptive methods (depot medroxyprogesterone acetate (DMPA), etonogestrel implant (Eng-Implant), levonorgestrel intrauterine device (Lng-IUD) and ParaGard® T 380A Intrauterine Copper Contraceptive) on: (1) HIV target immune cells within the female genital mucosa; (2) markers of T-cell activation and trafficking within the female genital mucosa; and (3) secreted cytokines and chemokines within the female genital mucosa.

Official Title
-----------------
Impact of Hormonal Contraception on HIV Acquisition and Transmission Risk

Conditions
-----------------
HIV, Contraception

Intervention / Treatment
-----------------
* Drug: Depot medroxyprogesterone acetate (DMPA)
* Device: Etonogestrel implant (Eng-Implant)
* Device: Levonorgestrel intrauterine device (Lng-IUD)
* Device: ParaGard® T 380A Intrauterine Copper Contraceptive


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female Age 18-45 years Normal menses (22-35 day intervals) for at least 3 cycles Intact uterus and cervix Interested in to DMPA, Eng-Implant or Lng-IUD or ParaGuard Willing to delay initiation of hormonal contraception for up to 1 month Willing to use condoms or abstain from sexual intercourse for at least 48 hours before each genital tract sampling (condoms will be made available) Able and willing to provide informed consent, and undergo serial blood and cervicovaginal lavage (CVL) sampling Negative HIV screening Exclusion Criteria: Pregnant within the last 3 months Breastfeeding History of loop electrosurgical excision procedure, conization, or cryosurgery within the past year Use of hormonal contraception or IUD in the past 6 months Known history of medical condition that would interfere with the conduct of the study Symptomatic vaginal infection or genital ulcer disease at screening Taking medications that interact with selected contraceptive Contraindications to selected contraceptive per the Centers for Disease Control and Prevention (CDC) medical eligibility criteria or judgment of clinician

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Depot medroxyprogesterone acetate (DMPA)<br>DMPA will be administered every 12 weeks at 150 mg by intramuscular (IM) injection at week 3 of study enrollment and repeated at week 15. | Drug: Depot medroxyprogesterone acetate (DMPA)<br>* DMPA will be administered every 12 weeks at the standard dose of 150 mg IM, beginning from week 3 of study enrollment and repeated at week 15.<br>* Other names: Depo Provera;|
| Experimental: Etonogestrel implant (Eng-Implant)<br>A standard Nexplanon rod Implant will be placed at study week 3. | Device: Etonogestrel implant (Eng-Implant)<br>* A standard nexplanon rod implant will be placed at study week 3 by a trained clinician.<br>* Other names: Nexplanon;|
| Experimental: Levonorgestrel intrauterine device (Lng-IUD)<br>A standard Mirena IUD will be placed at study week 3. | Device: Levonorgestrel intrauterine device (Lng-IUD)<br>* A standard Mirena IUD will be placed at study week 3 by a trained clinician.<br>* Other names: Mirena;|
| Experimental: ParaGard® T 380A Intrauterine Copper Contraceptive<br>A standard ParaGuard IUD will be placed at study week 3. | Device: ParaGard® T 380A Intrauterine Copper Contraceptive<br>* A standard ParaGuard IUD will be placed at study week 3 by a trained clinician.<br>* Other names: ParaGuard;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of HIV Target Immune Cells Within Female Genital Mucosa and Blood | Following exposure to HIV, initial infection occurs at the genital mucosa and may involve complex interactions between a number of HIV target immune cells. HIV often uses C-C Chemokine Receptor Type 5 (CCR5) for entrance into target immune cells, causing infection of the cell. The amount of CCR5 expressing macrophages is associated with HIV infection. Cluster of differentiation 4 (CD4) T Cells are targeted and infected by HIV and CD4 percentages are used to assess immune status. CD4 counts vary by individuals and generally decrease with HIV infection. | Week 1, Week 17 | 
| Ratio of CD4/Cluster of Differentiation 8 (CD8) T-Cells Within Female Genital Mucosa and Blood | CD4/CD8 ratios above 1 indicate a strong immune system while lower ratios indicate a viral infection. | Week 1, Week 17 | 
| Percent of Markers of T-cell Activation and Trafficking Within the Female Genital Mucosa and Blood | T cell activation correlates with HIV infection progression and this study seeks to gain better understanding of these underlying mechanisms by assessment of HIV target cells. Changes in cluster of differentiation 38 (CD38) expression are indicators of HIV disease progression with increases seen in CD38+ when a chronic HIV infection is progressing. Human leukocyte antigen-antigen D related (HLA-DR)+ expression appears to be involved in HIV proliferation. | Week 1, Week 17 | 
| Concentration Levels of Secreted Cytokines and Chemokines Within the Female Genital Mucosa and Blood | The concentration levels of interleukin 1 (IL-1) family cytokines and interferon gamma-induced protein 10 (IP-10) chemokines were determined using multiplex Luminex® assays combined with a customized multi-analytical panel of 22 human cytokines and chemokines. IL-1 and IP-10 have been found to influence recruitment of HIV target cells to the female reproductive tract and this study is examining changes in IL-1 and PI-10 to gain further understanding of these mechanisms. | Week 1, Week 17 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV-negative