Impact of Hormonal Contraception on HIV Acquisition and Transmission Risk

Phase 4

Completed

• Conditions: HIV; Contraception
• Interventions: Drug: Depot medroxyprogesterone acetate (DMPA); Device: Etonogestrel implant (Eng-Implant); Device: Levonorgestrel intrauterine device (Lng-IUD); Device: ParaGard® T 380A Intrauterine Copper Contraceptive

• Registration Number: NCT02357368
• Lead Sponsor: Lisa Haddad

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.

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-03
• Study First Submitted QC: 2015-02-05
• Study First Posted: 2015-02-06
• Primary Completion: 2019-10-23
• Study Completion: 2019-10-23
• Status Verified: 2020-10
• Results First Submitted: 2020-10-23
• Results First Submitted QC: 2020-10-23
• Last Update Submitted: 2020-10-23
• Results First Posted: 2020-11-18
• Last Update Posted: 2020-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 59

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Depot medroxyprogesterone acetate (DMPA)	Depot medroxyprogesterone acetate (DMPA)	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.
Etonogestrel implant (Eng-Implant)	Etonogestrel implant (Eng-Implant)	A standard Nexplanon rod Implant will be placed at study week 3.
Levonorgestrel intrauterine device (Lng-IUD)	Levonorgestrel intrauterine device (Lng-IUD)	A standard Mirena IUD will be placed at study week 3.
ParaGard® T 380A Intrauterine Copper Contraceptive	ParaGard® T 380A Intrauterine Copper Contraceptive	A standard ParaGuard IUD will be placed at study week 3.

Primary Outcome Measures

Name	Time	Method
Percent of HIV Target Immune Cells Within Female Genital Mucosa and Blood	Week 1, Week 17	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.
Ratio of CD4/Cluster of Differentiation 8 (CD8) T-Cells Within Female Genital Mucosa and Blood	Week 1, Week 17	CD4/CD8 ratios above 1 indicate a strong immune system while lower ratios indicate a viral infection.
Percent of Markers of T-cell Activation and Trafficking Within the Female Genital Mucosa and Blood	Week 1, Week 17	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.
Concentration Levels of Secreted Cytokines and Chemokines Within the Female Genital Mucosa and Blood	Week 1, Week 17	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.

Trial Locations

Locations (4)

Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

The Ponce de Leon Center of the Grady Health System; 🇺🇸 Atlanta, Georgia, United States

Grady Health System; 🇺🇸 Atlanta, Georgia, United States

Emory University Clinical Research Network; 🇺🇸 Atlanta, Georgia, United States