The Evidence for Contraceptive Options and HIV Outcomes Trial

Conditions

HIV, Contraception

Keywords

HIV infection, DepoLevonorgestrel, Contraception, DMPA, Copper IUD, Levonorgestrel implant, IUD

Brief summary

The ECHO Study is an open-label randomized clinical trial that will compare three highly effective, reversible methods of contraception (including a non-hormonal method) to evaluate whether there is a link between use of any of these methods and increased risk of acquiring HIV infection. A randomized clinical trial among about 7,800 women in four countries, ECHO will deliver evidence to support and guide individual, policy and programmatic decisions on contraception for women at risk of acquiring HIV infection.

Detailed description

Approximately 7800 sexually active, HIV-negative women, 16-35 years old, seeking effective contraception, willing to be randomized to any of the study arms, and not desiring pregnancy for the duration of study participation will be randomly allocated to one of three study arms in a 1:1:1 ratio: depot medroxyprogesterone acetate (DMPA), levonorgestrel (LNG) implant, copper intrauterine device (IUD). Enrollment will require an estimated 18 months and the total duration of the clinical portion of the study is estimated to be 36 months. The primary objective is to compare the risks of HIV acquisition between women randomized to DMPA, levonorgestrel (LNG) implant, and copper IUDs. Secondary objectives are to compare: 1) pregnancy rates among women randomized to DMPA, LNG implant, and copper IUDs, 2) rates of serious adverse events among women randomized to DMPA, LNG implant, and copper IUDs, 3) rates of adverse events that lead to method discontinuation among women randomized to DMPA, LNG implant, and copper IUDs, and 4) contraceptive method continuation rates among women randomized to DMPA, LNG implant, and copper IUDs. Tertiary objectives are to evaluate: 1) whether age modifies the relationship between the three contraceptive methods and HIV acquisition, 2) whether HSV-2 status modifies the relationship between the three contraceptive methods and HIV acquisition, and 3) early HIV disease progression among sero-converters randomized to DMPA, LNG implant, and copper IUDs. Ancillary studies will assess biological mechanisms at the interface of contraceptives and markers of HIV risk.

Susan Morrison, Joanne Batting, Valentine Wanga, Ivana Beesham, Jennifer Deese et al. (21 authors)

JAIDS Journal of Acquired Immune Deficiency Syndromes2024-08-01

10.1097/qai.0000000000003497

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

Hofmeyr GJ, Singata-Madliki M, Batting J, Balakrishna Y, Morroni C.

2024-03-084 citations

10.1186/s12905-024-02990-8

Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial

Bryan P. Brown, Colin Feng, Ramla F. Tanko, Shameem Z. Jaumdally, Rubina Bunjun et al. (20 authors)

Nature Communications2023-01-3018 citations

10.1038/s41467-023-36002-4

Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial

Rubina Bunjun, Tanko F Ramla, Shameem Z. Jaumdally, Laura Noël‐Romas, Hossaena Ayele et al. (20 authors)

Clinical Infectious Diseases2022-08-0912 citations

10.1093/cid/ciac284

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial

Ivana Beesham, Leila E. Mansoor, Dvora Joseph Davey, Thesla Palanee‐Phillips, Jenni Smit et al. (16 authors)

JAIDS Journal of Acquired Immune Deficiency Syndromes2022-06-09

10.1097/qai.0000000000003023

High HIV incidence among young women in South Africa: Data from a large prospective study

Thesla Palanee‐Phillips, Helen Rees, Kate B. Heller, Khatija Ahmed, Joanne Batting et al. (24 authors)

PLoS ONE2022-06-0333 citations

10.1371/journal.pone.0269317

Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial

Rebecca Ryan, Aamirah Mussa, Mandisa Singtaa-Madliki, Joanne Batting, Yusentha Balakrishna et al. (7 authors)

Frontiers in Global Women s Health2022-05-204 citations

10.3389/fgwh.2022.887541

The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant

Ramla F. Tanko, Rubina Bunjun, Smritee Dabee, Shameem Z. Jaumdally, Maricianah Onono et al. (20 authors)

The Journal of Infectious Diseases2022-03-086 citations

10.1093/infdis/jiac084

Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial

Nelly Mugo, Randy M. Stalter, Renee Heffron, Helen Rees, Caitlin W. Scoville et al. (52 authors)

Clinical Infectious Diseases2021-12-144 citations

10.1093/cid/ciab1027

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study.

Donnell D, Beesham I, Welch JD, Heffron R, Pleaner M, Kidoguchi L, Palanee-Phillips T, Ahmed K, Baron D, Bukusi EA, Louw C, Mastro TD, Smit J, Batting JR, Malahleha M, Bailey VC, Beksinska M, Rees H, Baeten JM, ECHO Trial Consortium.

2021-06-1127 citations

10.1016/s2352-3018(21)00048-5

Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial.

Beksinska M, Issema R, Beesham I, Lalbahadur T, Thomas K, Morrison C, Hofmeyr GJ, Steyn PS, Mugo N, Palanee-Phillips T, Ahmed K, Nair G, Baeten JM, Smit J.

2021-04-0615 citations

10.1016/j.eclinm.2021.100800

Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial

Mandisa Singata‐Madliki, Florence Carayon‐Lefebvre d’Hellencourt, Theresa A Lawrie, Yusentha Balakrishna, G Justus Hofmeyr

International Journal of Gynecology & Obstetrics2021-01-1516 citations

10.1002/ijgo.13594

Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives

Sharon L. Achilles, Leslie A. Meyn, Felix Mhlanga, Allen Matubu, Kevin A. Stoner et al. (8 authors)

American Journal of Reproductive Immunology2020-06-1314 citations

10.1111/aji.13287

HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial.

Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium.

2019-06-13232 citations

10.1016/s0140-6736(19)31288-7

Referee report. For: Rationale and design of a multi-center, open-label, randomised clinical trial comparing HIV incidence and contraceptive benefits in women using three commonly-used contraceptive methods (the ECHO study) [version 1; referees: 1 approved]

Audrey Pettifor

Faculty of 1000 Research Ltd2018-01-01

10.21956/gatesopenres.13835.r26174

Referee report. For: Rationale and design of a multi-center, open-label, randomised clinical trial comparing HIV incidence and contraceptive benefits in women using three commonly-used contraceptive methods (the ECHO study) [version 1; referees: 2 approved]

Sten H. Vermund

Faculty of 1000 Research Ltd2018-01-01

10.21956/gatesopenres.13835.r26178

Psychological, behavioural and physiological effects of three long-acting reversible contraception (LARC) methods: protocol for an ancillary study of the ECHO randomised trial

Mandisa Singata‐Madliki, G Justus Hofmeyr, Florence Carayon-Lefebvre d’Hellencourt, Theresa A Lawrie

BMJ Open2017-11-014 citations

10.1136/bmjopen-2017-019205

Rationale and design of a multi-center, open-label, randomised clinical trial comparing HIV incidence and contraceptive benefits in women using three commonly-used contraceptive methods (the ECHO study).

Hofmeyr GJ, Morrison CS, Baeten JM, Chipato T, Donnell D, Gichangi P, Mugo N, Nanda K, Rees H, Steyn P, Taylor D, ECHO Trial Team.

2017-01-0126 citations

10.12688/gatesopenres.12775.2

Interventions

DRUGDMPA

Women randomized to DMPA, will receive an intramuscular injection of DMPA (medroxyprogesterone acetate sterile aqueous suspension 150 mg per 1 mL) at enrolment. Subsequent injections will be given every 3 months (i.e., at quarterly study visits) at the study site.

DRUGLNG

Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians.

DRUGCopper IUD

Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

16 Years to 35 Years

Healthy volunteers

Yes

Inclusion criteria

* 16-35 years of age (previously pregnant 16 and 17 year olds, where permissible by national regulations and local IRB approval) * HIV-seronegative * Wants to use effective contraception * Is able and willing to provide written informed consent * Agrees to be randomized to either DMPA, LNG implant, or copper IUD * Agrees to use assigned method for 18 months * Agrees to follow all study requirements * Intends to stay in the study area for the next 18 months, and willing and able to provide adequate locator information * If has had a recent third trimester birth, is at least 6 weeks postpartum * Is sexually active (has had vaginal sex within the last 3 months) or was pregnant within the last 3 months * Agrees not to participate in studies of drugs or vaccines or any other clinical research study while participating in this study.

Exclusion criteria

* Reported medical contraindications (WHO MEC Category 3 or 4) to DMPA, LNG implant, or copper IUDs, including: recent septic abortion; suspicious unexplained vaginal bleeding; breast, cervical, uterine, or ovarian cancer; high BP or heart disease, venous thromboembolism, stroke, or diabetes; liver disease or liver tumours; use of liver enzyme inducing medications * Is found to have pelvic tuberculosis or uterine fibroids with distortion of the uterine cavity on pelvic exam * Has untreated mucus and purulent cervicitis on exam, untreated pelvic inflammatory disease (PID), or untreated known gonorrhea or chlamydia * Has received a DMPA or NET-En injection in the last 6 months * Has used an implant or an IUD in the last 6 months * Is pregnant or intending to become pregnant in the next 18 months * Has had a hysterectomy or sterilization * Has previously participated in the study * Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe or complicate data interpretation.

Design outcomes

Primary

Measure	Time frame	Description
Compare risks of HIV acquisition between women randomized to DMPA, LNG and copper IUD	From enrollment to 18 months	HIV infection as measured by documented HIV seroconversion occurring post-enrolment

Secondary

Measure	Time frame
Compare pregnancy rates among women randomized to DMPA, LNG and copper IUD	From enrollment to 18 months
Compare rates of adverse events that lead to discontinuation among women randomized to DMPA, LNG and copper IUD	From enrollment to 18 months
Compare contraceptive continuation rates among women randomized to DMPA, LNG and copper IUD	From enrollment to 18 months
Compare SAEs among women randomized to DMPA, LNG and copper IUD	From enrollment to 18 months

Countries

Eswatini, Kenya, South Africa, Zambia

Outcome results

None listed