- 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
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: Interim data announced in March 2018 from two subsequent open-label studies, DREAM and HOPE, found increases in product use over the Phase III trials and suggest increased efficacy—by approximately 50 percent, based on statistical modeling. More recent data from DREAM suggest a 59 percent reduction in HIV risk. These findings are limited by the lack of placebo comparison groups in the open-label studies. Together, these results suggest that when women know the ring helped reduce HIV risk in large clinical trials, they are more likely to use it and see greater protection.
What is the ring's status and what are the next steps?
The ring is currently under review by the European Medicines Agency, and regulatory submissions to the South African Health Products Regulatory Authority and the US Food and Drug Administration are planned for 2019. 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 populations: Studies are planned 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. A safety study called REACH is underway in Africa among young women 16-21, and two safety studies are planned among pregnant and breastfeeding women in Africa (DELIVER and B-Protected, respectively).
Next-generation products: In addition, the monthly ring is a platform technology for next-generation products that could offer greater convenience, such as a longer-acting dapivirine ring that could be used for three months, and have widespread 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; 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.
Two open-label studies, DREAM and HOPE, launched in July 2016 to provide the ring to former Phase III trial participants for one year and to gain insights into how women will use the ring now that they know the ring was found to help reduce HIV risk in the Phase III studies. HOPE completed in October 2018 and DREAM completed in January 2019, with final results for both studies expected in 2019.
- Interim open-label extension study results:
- Pooled Phase III trial results (July 2017): IAS 2017 abstract and presentation
- Primary Phase III trial results (Feb. 2016):