Dapivirine Vaginal Ring

dapivirine ring

The first microbicide to be submitted for regulatory approval, the dapivirine vaginal ring, developed by the International Partnership for Microbicides (IPM) for HIV prevention, received a positive opinion from the European Medicines Agency (EMA) in July of 2020.

The ring, made of silicone, is inserted in the vagina and slowly releases dapivirine, an antiretroviral drug, over the course of one month. It is woman-controlled (a woman inserts and removes the ring herself) and releases active drug at the site of potential infection in the vagina, with very low systemic uptake (affecting the whole body).

scale-up process

Regulatory Status

IPM, the ring's developer, applied to the European Medicines Agency (EMA) for review of the ring under Article 58. This procedure allows the EMA, in cooperation with the World Health Organization (WHO), to provide a scientific opinion on the safety, efficacy and quality of medicines that would be marketed exclusively outside of the European Union—specifically in low- and middle-income countries—for diseases of major public health interest.

In July of 2020, the EMA gave a positive scientific opinion on the public health benefits of the ring for use by women in low- and middle-income countries outside of the European Union. The positive opinion also said there should be a commitment to do a post-authorization efficacy study. This study would enroll cisgender women aged 18-25 to better understand efficacy, and to complement existing data on potential drug resistance. The EMA’s positive opinion helps move the ring from a research product to a real tool that women can use.

Next Steps

The WHO can now convene a guideline development committee to review the dapivirine vaginal ring as part of its HIV/AIDS treatment and prevention guidelines with possible recommendations on the ring’s use. WHO may also now begin to “prequalify” the ring, a process to evaluate whether a medicine meets global standards for quality, safety and efficacy. WHO prequalification can facilitate national regulatory review and guideline development. Many African national regulatory agencies use WHO prequalification to determine which new products they approve.

IPM also plans to submit regulatory applications to the US Food & Drug Administration (FDA) and to various African regulatory bodies.

For the latest information, visit IPM's website here.

Click to see next steps in the regulatory plan

A positive opinion from the EMA can facilitate registration in priority African countries. An Article 58 review can also shorten the timeline for possible WHO prequalification, a process through which WHO evaluates whether a medicine meets global standards for quality, safety and efficacy.

For many countries, an opinion from a stringent regulatory authority such as the EMA along with WHO guidelines and prequalification will help advance national-level regulatory decision-making. For more information on the regulatory process, access the Dapivirine Ring Market Introduction Considerations deck here.

regulatory overview

Planning for Introduction

A robust plan for ring introduction is in place and the positive EMA opinion moves the ring closer to potential introduction and scale-up in communities where it is most needed. IPM has chosen to focus its initial planning for introduction in Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe.

These countries were selected due to the public health need and their participation in ring studies, which could facilitate the product’s introduction if it is approved. This planning involves studies, information gathering and collaboration with many organizations and key stakeholders.

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The Common Agenda

The Common Agenda serves as a shared guide for stakeholders working on activities required for the introduction of the dapivirine vaginal ring. The Common Agenda is designed to streamline and accelerate collective efforts.

graphic detailing common agenda components — details available if you clickthrough

Learn more about the Common Agenda.

Evidence and Research

Information on Phase III trials, open label extension studies, ring studies involving adolescent girls and young women, and pregnancy and breastfeeding studies is available below.

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Phase III Trials

  • Between 2012 and 2016, IPM and the Microbicide Trials Network (MTN) conducted two Phase III “sister studies” (called The Ring Study and ASPIRE) to test the ring’s effectiveness. With the help of over 4,500 women participants in Malawi, South Africa, Uganda and Zimbabwe, they found that ring use reduced the rate of new HIV infections by approximately 30 percent overall and by 45 percent among the women who used it at least some of the time. Notably, women older than 21 were more likely than younger women to leave the ring in place. Research is now underway to learn more about how younger women perceive the ring and what might influence their interest in using it.

Open Label Extension (OLE) Studies

  • Two open-label extension studies, DREAM and HOPE, launched in July 2016 to collect additional data on the ring. DREAM completed in January 2019 and HOPE completed in October 2018. Women in both studies knew that the ring provided to them was the active ring, and not a placebo, which was already shown to lower HIV risk and raised no safety concerns during the Phase III trials.
  • Results from DREAM, announced during the South Africa AIDS Conference in 2019, showed increase use of the ring among participants. Analyses of DREAM results using statistical modeling also suggest that the overall HIV incidence rate among participants was 63 percent lower than would be expected without use of the dapivirine ring. Read the IPM press release on the DREAM study here.
  • HOPE results were reported at the International AIDS Society 2019 conference in Mexico City. Because women who participated in HOPE were able to accept or decline use of the ring, researchers were also able to assess demand for the ring among participants. Results from HOPE showed that the majority of participants chose the ring throughout their year of participation in the trial, and among those women, a similar trend toward increased ring use was observed as with the DREAM study. Using statistical modeling, HOPE researchers were also able to estimate an HIV risk reduction of approximately 39 percent among all women who participated in the study, including those who chose not to use the dapivirine ring. Read the MTN press release on HOPE here.

Use by Adolescent Girls and Young Women

  • The REACH study, which launched in early 2019, is exploring how adolescent girls and young women in sub-Saharan Africa use the monthly dapivirine ring and daily oral PrEP, and their preferences for these approaches. REACH will enroll 300 young women ages 16 to 21 in South Africa, Uganda, and Zimbabwe. This study will also provide more information on the safety of dapivirine ring and oral PrEP among this age group.
  • MTN-023/IPM-030, or “iMatter”, was the first study to evaluate the dapivirine ring among adolescent girls. iMatter showed that the ring was acceptable and raised no safety concerns among girls under the age of 18 living in the United States. Results from this randomized, placebo-controlled trial were presented at IAS 2017.

Use by Pregnant and Breastfeeding Women

Two studies to be led by MTN are planned among pregnant and breastfeeding women in Malawi, Uganda, South Africa and Zimbabwe. Pending ethics and in-country approvals, MTN-042 is expected to start by late 2019, and MTN-043 could begin during the first months of 2020.

  • MTN-042, or the DELIVER study, will assess the safety of the monthly dapivirine vaginal ring and Truvada as daily oral PrEP (pre-exposure prophylaxis) in pregnant women. Of the 750 women who will be enrolled, 500 will use the vaginal ring. The study is the first to be conducted of the dapivirine ring during pregnancy.
  • MTN-043, or the B-PROTECTED study, will evaluate the safety of dapivirine ring and oral PrEP use by women who are breastfeeding. B-PROTECTED will enroll up to 200 mothers and their breastfed babies.

Other Ring Studies

Ring Resources

Additional resources are available on planning for introduction, learning about the potential impact of the ring, marketing, demand creation and advocacy. For a one-page overview of ring resources, click here.

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Planning for Introduction

Understanding country-level questions and interest in the ring is a critical part of planning. Learning from the introduction of and experiences with other products, such as other HIV prevention products or other types of vaginal rings, can also inform planning.

Potential Impact of the Ring

Several modeling efforts have demonstrated the potential impact, and in some cases the cost and cost-effectiveness, of a monthly dapivirine ring.

Marketing and Demand Creation

With a clear understanding of potential users of the ring, marketing and demand creation strategies can be created.

Advocacy

Ensuring that women’s voices are heard is an essential component of ring introduction, just as it has been critical during clinical trials.

  • “Put A Ring On It: Four reasons to make the dapivirine ring an HIV prevention option for women and girls” – this June 2020 blog highlights the importance of the ring and its potential as a woman-initiated biomedical option to be added to the HIV prevention toolkit.
  • “What Young Women Want” (AVAC Partners, 2017) — this letter comes from a group of young African women and reflects their HIV prevention research priorities. It was submitted to the National Institutes of Health’s (NIH) Division of AIDS (DAIDS) during the open-comment period concerning the structure and agenda for its next funding cycle (2021-2027).
  • Inside My Purse — a blog by and for adolescent girls and young women across Africa. With sexual and reproductive health as its primary focus, the platform encourages visits and contributions from everyone who cares about promoting health, wellness and empowerment among young women.

Clinical Trial Results

  • Results from the Ring Study published in the New England Journal of Medicine (Dec 2016).
  • Results from ASPIRE published in the New England Journal of Medicine (Dec 2016).
  • Results from DREAM, announced during the South Africa AIDS Conference in 2019. Read the IPM press release on the DREAM study here.
  • Results from HOPE, announced at the International AIDS Society 2019 conference in Mexico City. Read the MTN press release on the HOPE results here.
  • What’s Next for the Dapivirine Ring — In this episode of Px Pulse, Zeda Rosenberg, CEO of the International Partnerships for Microbicides, explains the latest findings and spells out how, when, where and if the ring might become an available tool. A trial participant and community leader in Uganda pulls back the curtain on the ups and downs of using the ring, and a Ugandan investigator with the REACH study, Carolyne Akello of the Makere University-Johns Hopkins University Research Collaboration, explains the importance of this trial, the next step in testing the potential of this monthly vaginal ring for young women.

The Basics — Ring Background Resources


Last updated August 13, 2020.