Impact of Hormonal Contraception on HIV Acquisition and Transmission Risk

NCT02357368 | Completed Phase 4 Results FDA Drug FDA Device

• 2 other identifiers: IRB000725495K23HD078153-05
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 4

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.

Conditions

HIV; Contraception

Keywords

HIV-negative

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (4)

Depot medroxyprogesterone acetate (DMPA)

EXPERIMENTAL

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)

Etonogestrel implant (Eng-Implant)

EXPERIMENTAL

A standard Nexplanon rod Implant will be placed at study week 3.

Device: Etonogestrel implant (Eng-Implant)

Levonorgestrel intrauterine device (Lng-IUD)

EXPERIMENTAL

A standard Mirena IUD will be placed at study week 3.

Device: Levonorgestrel intrauterine device (Lng-IUD)

ParaGard® T 380A Intrauterine Copper Contraceptive

EXPERIMENTAL

A standard ParaGuard IUD will be placed at study week 3.

Device: ParaGard® T 380A Intrauterine Copper Contraceptive

Interventions

Depot medroxyprogesterone acetate (DMPA) DRUG

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.

Also known as: Depo Provera

Depot medroxyprogesterone acetate (DMPA)

Etonogestrel implant (Eng-Implant) DEVICE

A standard nexplanon rod implant will be placed at study week 3 by a trained clinician.

Also known as: Nexplanon

Etonogestrel implant (Eng-Implant)

Levonorgestrel intrauterine device (Lng-IUD) DEVICE

A standard Mirena IUD will be placed at study week 3 by a trained clinician.

Also known as: Mirena

Levonorgestrel intrauterine device (Lng-IUD)

ParaGard® T 380A Intrauterine Copper Contraceptive DEVICE

A standard ParaGuard IUD will be placed at study week 3 by a trained clinician.

Also known as: ParaGuard

ParaGard® T 380A Intrauterine Copper Contraceptive

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lisa Haddad: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (4)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

The Ponce de Leon Center of the Grady Health System

Atlanta, Georgia, 30308, United States

Location

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Emory University Clinical Research Network

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

Medroxyprogesterone Acetate

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Lisa Haddad, MD
• Organization: Emory University

lisa.haddad@emory.edu

404-778-1385

Study Officials

• Lisa Haddad, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Asscoiate Professor

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: February 1, 2015
• Primary Completion: October 23, 2019
• Study Completion: October 23, 2019
• Last Updated: November 18, 2020
• Results First Posted: November 18, 2020

Record last verified: 2020-10

Locations

US (4)