ECHO

Background

• Women worldwide need family planning, and in Africa, the use of hormonal contraception, and especially Depo, provide women with a long-acting, reversible and safe option for birth control.
  More than 150 million women around the world use hormonal contraceptives.
• African women are at high risk of HIV.
  16 million women aged 15 years and older are living with HIV; 80% live in sub-Saharan Africa
  Young women 15–24 years old in sub-Saharan Africa are twice as likely as young men to be living with HIV.

African countries with HIV prevalence also have high rates of women using hormonal contraception

• The reasons for this are unclear.
• There is confusing data about whether there is a link between using some contraceptives and an increased risk of contracting HIV.

Objectives

Primary objective

• To compare the risks of HIV acquisition between women randomised to DMPA, levonorgestrel (LNG) implants, and copper IUDs

Secondary and tertiary objectives

• Pregnancy, safety, contraceptive continuation

Why do we need the ECHO Study?

• For over 25 years, the world has lived with the uncertainty about whether or not use of hormonal contraceptives increases HIV risk.
• ECHO aims to answer this critical public health question of the possible risks (HIV acquisition) and benefits (pregnancy prevention) of the three commonly-used, effective contraceptive methods among women who desire contraception.

Purpose of the ECHO Study

When comparing women’s use of the contraceptives— Depo, Jadelle and IUD:

• Is there an increased risk of acquiring HIV when they use one method over the others?
• Are there more or less side effects of each method?
• Are the pregnancy rates the same?
• How well do women stay on each of the three contraceptive methods?

ECHO Sites

The study will take place at 12 sites across Eastern and Southern Africa, including sites in:

1. Kenya – Kisumu
2. South Africa
3. Swaziland
4. Zambia

Who can participate in the ECHO study

• Sexually active women 16-35 years old
• HIV negative and willing to be tested
• Seeking effective contraception
• Do not want to become pregnant for the duration of study participation
• Willing to be randomised to any of the three contraceptives being tested
• Willing to give consent to participate

Voluntary and confidential

• All information shared with trial staff will kept confidential.
• Women are asked to be honest at all times in their answers to staff.
• Participation is voluntary and women may leave the study at any time they wish.

How the study works

Recruitment and Enrolling in the Study

1. Potential participants will be invited to the trial site to learn about the study
2. During an initial visit, they will learn about the risks and benefits and also about what is included in the visits (known as informed consent).
3. Women will learn about the 3 contraceptives being tested and asked if they would be willing to use any of the 3 products

What happens to women during the study who:

Become HIV positive

• Receive counseling
• Referred to local HIV care providers for on-going care according to the Nationa guidelines
• Remain in the study until completion and continue receiving services.
• Collection of data relevant to the additional study questions

Become Pregnant

• Receives care or referred for further care
• Discontinue her assigned method
• Remain in the study until completion
• Collection of data on HIV acquisition
• If pregnancy ends before completion of study, the woman will be encouraged to resume her allocated method or offered a choice of many method available at the clinic

Want to switch or stop Contraception

• Advised to come to the clinic to discuss her concerns and experience with the method.
• some women may wish to switch to another method after receiving counseling and treatment of any side effects.
• Participants may change methods at any time during the study
• Women who switch methods will remain in the study and will be seen accordingly

Grant PIs include:

NIH R01 – Renee Heffron & Heather Jaspan

FHI360 Fellowship – Jen Deese

ECHO biological mechanisms working group (BMWG)

• Liaises with ECHO ops committee and management committee
• Developed 1 standard set of samples to be collected at each participating site
• Membership is open to any ECHO team members (you can join if you want)

Biological mechanisms linking contraceptive use and HIV

• The primary goal of ECHO is to compare the risk of HIV infection among women assigned to use three different contraceptive methods (copper IUD, Jadelle implant, DMPA injectable)
• By addressing this goal, we will still not answer the question about how any of these contraceptives could increase HIV risk.
• Studies of biological mechanisms will permit to investigate possible pathways through which contraceptives could increase HIV risk
• In addition, these studies will provide important information for the development of new contraceptives and products that combine contraception with HIV prevention (called MPT or multipurpose prevention technologies
• To participate in the ancillary study, participants must be consented to protocol v3.0 or higher in ECHO.
• The consent form used for protocol v3.0 + includes the additional samples being collected for the ancillary study (BM).

In addition to consenting to participate in the ECHO study, participants must also agree to the additional samples being collected for the ancillary study.

Agreement might be documented within the consent form as a separate check box OR may be documented in the participant file.

Site-wide consistency in documentation of this agreement is necessary.

A participant can consent to ECHO protocol v3.0/v4.0 but refuse additional sample collection. In this case she is NOT eligible for the ancillary study.

If she changes her mind at a later visit and does agree to the additional sample collection, she can be enrolled in the ancillary study and contribute samples.

Like most studies of contraception and HIV, most studies of biological mechanisms have not been randomized.

Within ECHO, we can do randomized comparisons of how certain biologic markers change from enrollment to later months – and how these changes compare across all arms.

We can also look to see if seroconvertors experience any changes to a greater degree than non-seroconvertors.

1) Consented to ECHO protocol version 3.0 or higher

AND

2) Agreed to have additional samples collected

Newly enrolled participants will be consented to v3.0+ and asked to agree to additional sample collection at the enrolment visit

Participants in follow-up can be re-consented to v3.0+ & asked about agreement to sample collection at any visit

To participate in the ancillary study, participants must be consented to protocol v3.0 or higher in ECHO

The consent form used for protocol v3.0 + includes the additional samples being collected for the ancillary study.

Some of the assays to be conducted as part of this ancillary study involve understanding changes in genes and how genetic material might affect HIV acquisition.

Since these studies are supported by the National Institutes of Health (NIH), we must comply with their requirements to share the de-identified genetic data that is generated as a part of this testing in a databank.

The requirement to include the genetic data in the NIH databank makes it necessary to have an additional consent form in order to inform participants of this requirement so that they may decide whether or not they will allow their genetic data in the NIH databank. 

The NIH data bank includes de-identified data. It is not a specimen bank. 

Participants can sign the GDS consent at any visit.

Participants may change their mind at any point about whether or not they are willing to have their data stored in the NIH data bank.

Biological Mechanisms Ancillary Study procedures should not impede regular ECHO procedures. It is ideal to integrate ancillary study procedures into regular ECHO procedures where possible.

For example:

Collect blood for the ancillary study at the time of blood collection for ECHO HIV testing and archival

Collect genital samples for the ancillary study at the time of pelvic exams already part of regular ECHO procedures

Insert softcup at the beginning of the visit so that the participant can continue with other visit procedures such as counseling

Additional samples collected as part of the Biological Mechanisms Ancillary Study are collected at the following visits:

• Enrolment
• Month 1
• Quarterly (Months 3, 6, 9, 12, 15, and 18)

If the participant seroconverts during follow-up, additional sample collection will stop after HIV seroconversion is confirmed.

Laboratory requisition forms should be completed to document which samples were collected in the clinic.

Chain of custody of all samples should be documented when samples move from the clinic to the on-site laboratory and to an off-site laboratory (if applicable).

QC should be done in the clinic and in the lab to ensure samples are labeled correctly

Sample packs should be prepared before the participant visit and include all items needed for sample collection

Items in the sample pack should be labelled with the appropriate sample indicator (A, 1-9)

Remember that the 50mL tube for softcup collection must be weighed empty before being placed in the sample pack. Record the weight in permanent marker on the side of the tube.