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

NCT02038335 | Completed DMC

• 1 other identifier: PRO13080550
• Study Type: observational
• Target: 451
• Locations: 1 country
• Sites: 1

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.

Conditions

Contraception; HIV; Immune Cells (Mucosal and Systemic); Microbiota

Keywords

immune cells; contraception; intrauterine device; IUD; copper; microbiota; DMPA; etonogestrel; subdermal implant; NET-EN; Jadelle; Implanon; Cyclofem

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Vaginal microbiota (key microbes)

  Change from baseline at 3 months

• Serum hemoglobin

  Change from baseline at 6 months

• Serum concentration of estradiol and progesterone/progestin

  Change from baseline at 3 months

Study Arms (6)

DMPA

Depot medroxyprogesterone acetate

Drug: DMPA

NET-EN

Norethisterone enantate

Drug: NET-EN

MPA/E2

Medroxyprogesterone acetate and estradiol cypionate

Drug: MPA/E2

LNG-I

Levonorgestrel subdermal implant

Device: LNG-I

ENG-I

Etonogestrel subdermal implant

Device: ENG-I

Cu-IUD

Copper IUD

Device: Cu-IUD

Interventions

DMPA DRUG

Depot medroxyprogesterone acetate

Also known as: Depot medroxyprogesterone acetate (DMPA)

DMPA

NET-EN DRUG

Norethisterone enantate

Also known as: Norethisterone enantate (NET-EN)

NET-EN

MPA/E2 DRUG

Medroxyprogesterone acetate and estradiol cypionate

Also known as: Medroxyprogesterone acetate and estradiol cypionate (MPA/E2)

MPA/E2

LNG-I DEVICE

Levonorgestrel subdermal implant

Also known as: Levonorgestrel subdermal implant (LNG-I)

LNG-I

ENG-I DEVICE

Etonogestrel subdermal implant

Also known as: Etonogestrel subdermal implant (ENG-I)

ENG-I

Cu-IUD DEVICE

Copper IUD

Also known as: Copper IUD (Cu-IUD)

Cu-IUD

Eligibility Criteria

• Age: 18 Years - 34 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy women, age 18-34 years, who are HIV negative and non-pregnant.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Pittsburgh: lead
• University of Zimbabwe: collaborator

Study Sites (1)

UZ UCSF

Harare, Zimbabwe

Location

Related Publications (1)

• Achilles SL, Meyn LA, Mhlanga FG, Matubu AT, Stoner KA, Beamer MA, Chirenje ZM, Hillier SL. Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives. Am J Reprod Immunol. 2020 Sep;84(3):e13287. doi: 10.1111/aji.13287. Epub 2020 Jun 25.

  PMID: 32533883 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, plasma archive, vaginal swabs, serum, cervicovaginal lavage fluid

MeSH Terms

Interventions

N,N-dimethyl-4-anisidine; norethindrone enanthate; Medroxyprogesterone Acetate; estradiol 17 beta-cypionate

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sharon Achilles, MD, PhD

  University of Pittsburgh

  STUDY CHAIR

• Felix Mhlanga, MD

  University of Zimbabwe, University of California San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator and Protocol Chair

Study Record Dates

• First Submitted: January 8, 2014
• First Posted: January 16, 2014
• Study Start: February 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2020
• Last Updated: December 3, 2020

Record last verified: 2020-12

Locations

ZI (1)