- Acts against: HIV-1
- Delivery method: Silicone matrix vaginal ring
- Active ingredient: Dapivirine, an antiretroviral drug
- Length of action: One month, with a three-month ring in development
- Status: First regulatory review underway; additional open-label studies underway among adolescents & young women and pregnant women, and planned among breastfeeding women
Why is the dapivirine ring important?
Existing prevention methods have not done enough to stop the spread of HIV among women, who bear a disproportionate burden of the epidemic, particularly in sub-Saharan Africa. Pending regulatory approval, the monthly dapivirine ring would provide women with the first discreet, long-acting prevention option.
How does the dapivirine ring work?
The ring is made of a flexible silicone matrix polymer and contains the ARV dapivirine, an NNRTI, which is slowly released over the course of a month.
The ring delivers dapivirine directly at the site of potential infection, with low systemic absorption. Women insert the flexible, long-acting ring themselves into the vagina and replace it every month.
How effective is the ring?
Phase III studies: In 2016, two Phase III studies, The Ring Study and ASPIRE, announced that the monthly dapivirine ring helped reduce the risk of HIV-1 infection in women by approximately 30 percent overall and was well-tolerated with long-term use.
Open-label studies: In 2019, final results from the OLEs showed increases in ring use and modeling data suggest greater risk reduction—by over 50% across both studies—compared to the Phase IIIs. Although these modeling results are limited due to the lack of a placebo comparison group, they indicate an encouraging trend we hope to see continue if the ring is approved and rolled out.
What is the ring's status and what are the next steps?
The ring is currently under review by the European Medicines Agency with an opinion expected in 2020, and regulatory submissions are planned to the US Food and Drug Administration and the South African Health Products Regulatory Authority. IPM also plans to submit applications to other regulators in eastern and southern Africa, where women face the highest risk for HIV. IPM is working with a global network of government, donor, private and civil society partners to determine how the ring could best fit into HIV prevention programs and prepare for the potential rollout of the ring at an affordable cost, pending its approval.
Research with key groups: A set of studies is designed to help us understand how the ring can work for women at different times in their lives: when they are under age 18, and when they are pregnant or breastfeeding. Two safety studies in Africa are underway: one called REACH among young women 16-21 and one called DELIVER among pregnant women. In addition, a safety study is planned among breastfeeding women in Africa (B-Protected).
Follow-on products: In addition, the monthly ring is a platform technology for longer-acting products that could expand women’s options, such as a dapivirine ring that could be used for three months, and rings that have broader appeal, such as IPM’s three-month dapivirine-contraceptive ring designed to prevent both HIV and unintended pregnancy.
What is the dapivirine ring’s potential impact?
Modeling studies show that microbicides like the dapivirine ring would have a meaningful public health impact as part of a comprehensive HIV prevention portfolio and could avert infections that would not be prevented by another method.
If approved, the dapivirine ring would offer the first woman-centered, long-acting HIV prevention method and could be an important new self-initiated option for women, who bear the greatest burden of the global HIV/AIDS epidemic.
Who are IPM's research and manufacturing partners?
- ARV license: Janssen Sciences Ireland UC
- Development: Queens University Belfast
- Manufacturing and raw materials: QPharma; Omnichem; Trelyst
- Clinical trials: US National Institutes of Health-funded Microbicide Trials Network and research center partners in Africa
What is the ring's development history?
IPM brought the dapivirine ring from concept to Phase III clinical trials in just seven years. In 2004, IPM embarked on an extensive program of preclinical assessments of dapivirine in various formulations. To provide discreet, long-acting protection to women, IPM prioritized a ring formulation in 2010. IPM collaborated with partners to develop and evaluate early prototypes, ultimately advancing Ring-004 to late-stage clinical trials.
What is its clinical history?
IPM conducted two Phase I and one Phase I/II safety trials of the ring from 2009 to 2012, all of which found the ring to be safe and well-tolerated. Given the ring’s promise, IPM then launched two Phase III studies in 2012: The Ring Study, led by IPM, and ASPIRE, led by IPM’s clinical trial partner, the US National Institutes of Health-funded Microbicide Trials Network (MTN). These two studies enrolled approximately 4,500 women in Malawi, South Africa, Uganda and Zimbabwe to assess the ring’s efficacy and long-term safety. A package of smaller safety trials was also conducted to collect the safety data required by global and national regulatory authorities to seek licensure for the ring’s public use.
When the Phase III studies found the ring to help reduce HIV risk in 2016, two open-label studies, DREAM and HOPE, launched in July of that year to provide the ring to former Phase III trial participants for one year and to gain insights into how women use the product. HOPE completed in October 2018 and DREAM completed in January 2019, with final results for both announced in 2019.
- Open-label extension study results:
- DREAM final results: SA AIDS 2019 presentation and IPM press release
- HOPE final results: IAS 2019 abstract and presentation; MTN press release
- DREAM interim results: R4P 2018 abstract and presentation
- DREAM interim results: CROI 2018 abstract and presentation
- HOPE interim results: CROI 2018 abstract and presentation
- CROI 2018 press releases from IPM and MTN
- Pooled Phase III trial results (July 2017): IAS 2017 abstract and presentation
- Primary Phase III trial results (Feb. 2016):