The Dapivirine Vaginal Ring
The PrEP Vaginal Ring
The first topical HIV prevention method to be submitted for regulatory approval, the dapivirine vaginal ring (DVR) is a silicone ring, developed by the International Partnership for Microbicides (IPM).
The ring is inserted in the vagina and slowly releases an antiretroviral drug called dapivirine over the course of one month to help protect against HIV at the site of potential infection. Little of the drug is absorbed elsewhere in the body, making it unlikely to be found in high concentrations in the bloodstream and other body tissues. This may reduce side effects as well the risk of development of HIV resistance. Data from Phase III studies of the ring show no evidence that it increased resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), the class of ARV drug to which dapivirine belongs and which is also used in some treatment regimens.
Click here to access the Ring 101 Slide Deck — these slides give an overview of the DVR, including basic information about how it’s used, clinical trial results, user experience, and upcoming studies and products.
The dapivirine vaginal ring reduces the risk of HIV-infection, and offers a discreet and long-acting alternative to daily oral PrEP.
Today, women account for more than half of all people living with HIV globally, and face persistently high HIV-infection rates. But women face unique challenges when it comes to adhering to a daily pill due to gender inequity, social norms and other structural barriers.
Efficacy data shows that the ring reduces HIV risk by 35 percent, and recent data from open label extension studies suggest even higher protection, about a 50 percent reduction in HIV risk.
Modelling has shown that even a partially effective prevention option can have an important protective impact for women and their communities as part of a comprehensive HIV prevention strategy.
What is the status of the dapivirine vaginal ring’s approval?
Several African countries have approved the ring, and others are reviewing it. For insights on the full scope of PrEP uptake, including the ring, around the world, the PrEP Tracker as a spreadsheet offers a sortable database on PrEP uptake by country, by approved product, and additional data.
Like other PrEP products, the DVR does not protect against other STIs or unwanted pregnancy.
The ring does not reduce risk of chlamydia, gonorrhea, syphilis or herpes, or unwanted pregnancy. There are studies underway examining the safety of a combined dapivirine-levonorgestrel ring that would protect against both HIV infection and unwanted pregnancy, as well as different vaginal rings that combine antiretrovirals and other medications to prevent STIs.
Background on the regulatory process
In March 2021, the WHO released updated clinical recommendations on HIV prevention which included detailed guidance for the DVR as an additional prevention choice for women at substantial risk of HIV infection as part of a combination prevention package. This followed an initial announcement in January 2021 where the World Health Organization (WHO) recommended the ring. In November 2020, WHO prequalified the ring.
Prequalification involves evaluating whether a medicine meets global standards for quality, safety and efficacy. Many African national regulatory agencies consider WHO prequalification as they review new products. In July 2020, the European Medicines Agency (EMA) gave a positive opinion on the use of the ring by women in low- and middle-income countries outside of the European Union. IPM, the ring’s developer, submitted the ring to the EMA for review under Article 58.
This procedure allows the EMA, in cooperation with the WHO, to apply European Union (EU) standards to provide a scientific opinion on the safety, efficacy and quality of medicines that would be marketed exclusively outside of the EU—specifically in low- and middle-income countries—for diseases of major public health interest. The positive opinion also recommended a post-authorization efficacy study to better understand efficacy among cisgender women aged 18-25, and to complement existing data on potential drug resistance.
The FDA has not evaluated the ring. In December of 2021 the IPM announced it voluntarily withdrew its application to the FDA to consider approval of the ring. IPM said the decision came after feedback from an early review by FDA that it was unlikely to approve the ring for the US population “given the context of the current HIV prevention landscape for women in the United States.” US based advocates for women’s health and HIV prevention have criticized the move. And the decision has serious implications for global access.
PEPFAR, the largest provider of HIV treatment and prevention products in countries hardest hit by HIV, only procures ARV-based products that have been granted tentative approval or approval by The FDA’s Center for Drug Evaluation and Research (CDER).
People who may use the ring must have a leading role in the decisions that will govern how the ring is delivered. Their voices must be heard.
Prevention options that mitigate or eliminate barriers to access are essential. Key populations need effective options that work and fit into their lives. Each HIV prevention option has unique characteristics, and individuals may prefer a particular PrEP method for any number of reasons. Ensuring informed choice is key and is one of the main methods of advocates.
The ring is one strategy to help reduce HIV risk. For some people it will be the right one; for others, injectable cabotegravir for PrEP, oral PrEP, or another non ARV-based approach will be right. Research and development have created new options; now advocacy is needed to make them viable choices for people who need and want them.
Civil society advocates are able to reach and influence decision-makers at all levels, bolster community buy-in, support and inform demand generation activities, and mobilize resources. Advocates are working in their countries to build knowledge amongst civil society on new prevention options and helping to raise their voices on what matters most in developing introduction plans. In addition, advocates are engaging directly with PEPFAR and other funders to make the case for how important it is to support the ring rollout if it is to be accessible to those who want and can use it – to address their HIV prevention needs.
- Dapivirine Vaginal Ring Perspectives: Voices for Prevention — This video series, developed by the MOSAIC Project, features the voices of former participants in the research trials that tested the dapivirine vaginal ring. Videos from Kenya, South Africa, Zambia, Zimbabwe, and a compilation video showcase trial participants explaining why the ring works for them and their need for future access to this HIV prevention method.
- Guidelines for Dapivirine Ring Pilot Implementation Studies: Template Language for National-Level Guidance & Protocol Development — This tool provides adaptable guidelines for the design of implementation studies. Developed by the PROMISE Collaboration in close collaboration with USAID.
- Dapivirine Vaginal Ring Advocacy Messaging Resource Package – This is a toolkit for developing a messaging framework and implementation plan in support of advocacy activities for the dapivirine vaginal ring.