Clinical Trial on the Effects of Progestin-based Contraception in the Genital Tract of HIV-infected and Uninfected Women

NCT02103660 | Completed Phase 4 DMC

• 5 other identifiers: CDC-NCCDPHP-65121K01TW009657-01U48DP001944SIP 09-022UNCPM 1303
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the acceptability of randomization to contraceptive options and estimate the effect of progestin contraception on HIV genital shedding and inflammatory/immune perturbations in women who may or may not be on antiretroviral therapy, as well as in HIV-uninfected women controls. It is hypothesized that progestin-containing contraception will lead to inflammatory changes that may affect the local immune activity, influencing HIV acquisition or transmissibility risk.

Conditions

HIV; Contraception

Keywords

contraceptive implant; Depo-Medroxyprogesterone Acetate; Hormonal Contraception; progestin

Outcome Measures

Primary Outcomes (2)

• HIV viral load in the genital tract of HIV-infected women before and after initiation of progestin-containing contraception

  Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate indicating whether the measurement was taken before or after receiving the contraceptive method, and the null hypothesis will be tested using a z-test on this covariate.

  6 months post randomization; 24 months to 33 months post randomization

• HIV viral load in the genital tract of HIV-infected women by contraceptive type

  Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate for contraception arm, and the null hypothesis will be tested using a z-test on this covariate.

  6 months post randomization;24 months to 33 months post randomization

Secondary Outcomes (3)

• Impact of the type of progestin-containing contraception (injectable versus implant) on inflammatory/immune markers in the genital tract women.

  6 months post randomization

• Contraceptive efficacy in HIV-infected women

  6 months post randomization; 24 months to 33 months post randomization

• Interaction of progestin-based hormonal contraception and antiretroviral therapy

  6 months post randomization;24 months to 33 months post randomization

Study Arms (2)

Depo-Medroxyprogesterone Acetate

ACTIVE COMPARATOR

Half of women will be randomized to receive Depo-Medroxyprogesterone Acetate injections every 13 weeks

Drug: Depo-Medroxyprogesterone Acetate

Progestin Implant (Jadelle)

ACTIVE COMPARATOR

Half of women will be randomized to receive progestin implant.

Drug: Progestin Contraceptive (Jadelle)

Interventions

Depo-Medroxyprogesterone Acetate DRUG

150 mg Depo-Medroxyprogesterone Acetate administered every 13 weeks

Also known as: Depo provera, DMPA, injectable contraception

Depo-Medroxyprogesterone Acetate

Progestin Contraceptive (Jadelle) DRUG

2 implants containing 75 mg of levonorgestrel will be implanted and will last for up to 5 years

Also known as: Jadelle, Contraceptive Implant

Progestin Implant (Jadelle)

Eligibility Criteria

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

You may qualify if:

• Known HIV status, as documented by at least 2 concordant rapid tests (Determine and Uni-Gold, respectively). If the 2 rapid tests are discordant, then a confirmatory test will be done via Western blot.
• Female, pre-menopausal, age 18 to 45 years
• At least 2 regular, monthly cycles (\~21-35 days) in the 3 months preceding study enrollment.
• If on hormonal or intrauterine contraception in the past, they must have been off for at least 6 months. If they were previously using DMPA, their last -injection must have been ≥6 months ago.
• If recently pregnant, they must be at least 6 months postpartum
• Able and willing to provide informed consent
• Be otherwise a good candidate for study participation based on assessment by investigator or designee
• Interested in initiating a family planning method, specifically depot medroxyprogesterone acetate (DMPA) or the LNG implant (Jadelle)
• Willing to be randomized to receive either DMPA or LNG implant (Jadelle)
• Willing to wait 4-6 weeks after enrollment to receive this method and to use non-hormonal and non-intrauterine methods (such as abstinence or condoms) consistently during this period

You may not qualify if:

• Pregnancy (by clinical history or a positive urine pregnancy test at screening)
• Women currently using any hormonal contraceptive method
• Desire pregnancy within next 12 months
• Untreated visible genital ulcers or lesions on initial pelvic examination
• Known or suspected genital tract cancer (by clinical history or noted during initial pelvic examination).
• Contraindications to DMPA or LNG implant per the WHO medical eligibility114 criteria or judgment of clinician (contraindications include lactation within first 6 weeks postpartum, acute deep venous thrombosis or pulmonary embolism, lupus, migraine with aura, unexplained vaginal bleeding, current or history of breast cancer, severe cirrhosis, liver tumors, history of stroke, current or history of ischemic heart disease).
• Acute HIV infection (as documented by a known negative HIV test 6 months or less prior to screening).

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• National Institutes of Health (NIH): collaborator
• Fogarty International Center of the National Institute of Health: collaborator
• Bill and Melinda Gates Foundation: collaborator
• United States Agency for International Development (USAID): collaborator

Study Sites (1)

UNC-Project Lilongwe

Lilongwe, Malawi

Location

Related Publications (3)

• Haddad LB, Tang JH, Davis NL, Kourtis AP, Chinula L, Msika A, Tegha G, Hosseinipour MC, Nelson JAE, Hobbs MM, Gajer P, Ravel J, De Paris K. Influence of Hormonal Contraceptive Use and HIV on Cervicovaginal Cytokines and Microbiota in Malawi. mSphere. 2023 Feb 21;8(1):e0058522. doi: 10.1128/msphere.00585-22. Epub 2023 Jan 9.

  PMID: 36622252 DERIVED

• Zia Y, Tang JH, Chinula L, Tegha G, Stanczyk FZ, Kourtis AP. Medroxyprogesterone acetate concentrations among HIV-infected depot-medroxyprogesterone acetate users receiving antiretroviral therapy in Lilongwe, Malawi. Contraception. 2019 Nov;100(5):402-405. doi: 10.1016/j.contraception.2019.07.144. Epub 2019 Jul 30.

  PMID: 31374188 DERIVED

• Chinula L, Nelson JAE, Wiener J, Tang JH, Hurst S, Tegha G, Msika A, Ellington S, Hosseinipour MC, Mataya R, Haddad LB, Kourtis AP. Effect of the depot medroxyprogesterone acetate injectable and levonorgestrel implant on HIV genital shedding: a randomized trial. Contraception. 2018 Sep;98(3):193-198. doi: 10.1016/j.contraception.2018.05.001. Epub 2018 May 8.

  PMID: 29746813 DERIVED

MeSH Terms

Interventions

Medroxyprogesterone Acetate; N,N-dimethyl-4-anisidine; Contraceptive Agents

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses

Study Officials

• Jennifer Tang, MD, MSCR

  University of North Carolina

  STUDY CHAIR

• Lameck Chinula, MD

  UNC-Project Lilongwe

  STUDY CHAIR

• Athena P Kourtis, MD, PhD, MPH

  Centers for Disease Control and Prevention

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 4, 2014
• Study Start: April 8, 2014
• Primary Completion: March 31, 2017
• Study Completion: March 31, 2017
• Last Updated: March 19, 2018

Record last verified: 2018-03

Locations

MA (1)