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)
Open Access
- 13 March 2018
- journal article
- Published by F1000 Research Ltd in Gates Open Research
Abstract
Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate – DMPA, may increase women’s risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for up to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% relative increase in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.Keywords
Funding Information
- Bill and Melinda Gates Foundation (OPP1032115)
- United States Agency for International Development (AID-OAA-A-15-00045)
- Medical Research Council of South Africa
- Swedish International Development Cooperation Agency
This publication has 28 references indexed in Scilit:
- Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tractAIDS Research and Therapy, 2017
- An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in womenAIDS, 2016
- Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysisPLoS Medicine, 2015
- Time to focus on improving the contraceptive method mix in high HIV prevalence settings and let go of unanswerable questionsContraception, 2014
- Next steps for research on hormonal contraception and HIVThe Lancet, 2013
- Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV riskAIDS, 2013
- Sex Steroid Hormones, Hormonal Contraception, and the Immunobiology of Human Immunodeficiency Virus-1 InfectionEndocrine Reviews, 2009
- Copper containing, framed intra-uterine devices for contraceptionEmergencias, 2007
- Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and ZimbabweAIDS, 2007
- Subdermal implantable contraceptives versus other forms of reversible contraceptives or other implants as effective methods for preventing pregnancyCochrane Database of Systematic Reviews, 2007