26 June 2012

Interview: HIV Prevention Trial for Microbicide Ring Begins

Earlier this month, the International Partnership for Microbicides (IPM) announced the beginning of a clinical trial to determine whether a monthly vaginal ring containing the ARV dapivirine can help prevent HIV infection in women and is safe for long-term use. The trial is being conducted in four sites across South Africa with 1,650 women enrolled. IPM hopes to commence trials in Rwanda and Malawi in the next few months pending the clearance off a few regulatory hurdles.

Recent studies have indicated that ARVs can help prevent the spread of HIV between partners. “Sustained delivery of antiretrovirals in a vaginal ring could be a game-changer for prevention of HIV in women,” said Dr. Sharon Hillier, principal investigator of MTN. “The Microbicide Trials Network's partnership with IPM on effectiveness studies of this new technology will provide the most rapid and efficient pathway to licensure of this HIV prevention product.”

A vaginal ring is a promising advance since it requires only monthly replacement. Furthermore, the burden of HIV in Sub Saharan Africa (SSA) is squarely upon women. Women account for 60% of HIV cases in SSA and young women, ages 18 to 24, are twice as likely to be infected with HIV than young men.

The timing is important because the WHO is currently working on a new set of consolidated guidelines on antiretroviral treatment that is planned for release in July 2013. " It is planned to release recommendations on the use of ART in pre-exposure prophylaxis (PrEP) in serodiscordant couples and men who have sex with men, and guidance on the use of ART for prevention in sex workers, in July 2012," says the WHO. Next month's International AIDS Conference in Washington DC will be an important event in the lead up to the development of the guidelines.

A View From the Cave spoke with Dr. Zeda Rosenberg, CEO of the International Partnership for Microbicides, about the microbicide ring and its upcoming trial .

AVFTC: The studies are all taking place in Africa, but do you see this as a product that will have a global reach? When do you anticipate the ring being available to individuals?
Zeda: The Ring Study is currently taking place at four trial sites in South Africa and is expected to launch in Malawi and Rwanda as well, pending regulatory approvals. To date, IPM has focused its clinical trials in Africa, where the HIV epidemic has hit hardest. Over two-thirds of the global HIV burden falls on sub-Saharan Africa, and women and girls comprise 60 percent of people infected with the virus in Africa.

That said, IPM’s mission is to develop HIV prevention products for women and make them available to women in all developing countries, and we have negotiated agreements that allow us to distribute future products in these countries at the lowest possible cost. For example, IPM acquired dapivirine, the ARV drug used in the ring, through a royalty-free licensing agreement from Janssen Pharmaceuticals that will allow us to distribute the ring at an affordable cost in all developing countries.

Results from The Ring Study – and the broader ring licensure program – are expected in 2015, at which point IPM will seek regulatory approval for the product should the package of studies in IPM’s licensure program support its efficacy and long-term safety. In collaboration with partners, IPM is already laying the groundwork to help expedite roll-out and ensure affordability of the dapivirine ring, pending study results.
AVFTC: What are the advantages of providing ARVs through a vaginal ring? What are the drawbacks?
Z: IPM’s Ring Study builds on a number of recent trials that have demonstrated ARVs can successfully prevent HIV when used consistently. However, studies have shown that adherence can be a major barrier to the effectiveness of ARV-based prevention. The vaginal ring could provide a solution to this challenge. It delivers the ARV drug dapivirine continuously over one month, so women may be more likely to use the product consistently, which could help improve its efficacy.

In addition, because the vaginal ring delivers the ARV drug locally, with low systemic absorption, it could also help minimize side-effects and potentially reduce the risk for resistance. IPM is currently studying the ring’s potential to deliver long-acting combinations of ARVs, which may increase the level of protection, and is also developing a dual-purpose ring that would combine dapivirine with a contraceptive.

Preliminary safety and acceptability studies have shown IPM’s ring to be safe, easy-to-use and highly acceptable to both women and their partners. The Phase III study is designed to determine the long-term safety and efficacy of this product, and will provide additional details on the benefits and considerations of this promising technology.

Ultimately, a microbicide will prevent HIV only if it is used. Some women may prefer a long-acting product like the monthly ring, while others may prefer a daily gel used around the time of sex. We know that the more product options a woman has, the more likely she will be to find one that meets her needs and lifestyle — and to use it to protect herself. So it is essential that women are able to choose from a variety of HIV prevention options.
AVTC: Where will the ring be licensed/approved initially?
Z: IPM’s mission is to make safe and effective microbicides available to women in developing countries, where the need for new HIV prevention strategies is greatest. Should the dapivirine ring prove to be an effective HIV prevention option for women and safe for long-term use, IPM will seek regulatory approval for product licensure and collaborate with key partners to help ensure the ring is made available at low cost to women in developing countries as soon as possible. IPM will work with regulatory agencies in African countries, as well as in the United States and Europe, to accelerate the roll-out of an effective product.
AVFTC: What is the anticipated cost of the ring? How do you imagine it will reach people? Will it be a product sold through private markets, distributed at hospitals, or some sort of combination of private and public partners?
Z: The ultimate cost of the ring to women will depend on the scale of manufacturing and other financing mechanisms, which are being further researched. IPM is already laying the groundwork to help ensure that women would have rapid and affordable access to the dapivirine ring should the package of studies in IPM’s licensure program support its efficacy and long-term safety. IPM, in collaboration with key partners, is engaging in strategic access planning — and will be throughout the ring licensure program — to expedite the product’s roll-out and ensure affordable access to women in developing countries.

As a part of this process, IPM is working to optimize manufacturing processes, explore financing mechanisms and identify strategies for efficient scale-up in order to produce the dapivirine ring at the lowest possible cost. In addition, IPM is working to develop longer-acting options such as a 60- or 90-day ring which could potentially lower the overall cost to women who would need to purchase the product on a less frequent basis.

IPM is continuing to work with regulatory agencies, HIV prevention experts, local partners and others to identify appropriate distribution channels as part of our access plan, as well as marketing/public education campaigns for a potential product roll-out.
AVFTC: What type of reactions do the women have to the introduction of the product? What about their partners? What are general attitudes towards using vaginal rings compared to other contraceptives such as IUDs and condoms?
Z: A number of IPM safety and acceptability studies have found the ring to be highly acceptable to women, and their partners also expressed support for the ring. Made of flexible silicone, the ring is easy to insert and remove, and most women don’t notice or feel the product during sex. Nearly every woman in IPM’s studies has expressed that she would use the ring for HIV prevention.

The ring fills a critical gap in existing HIV prevention methods because, unlike other HIV prevention technologies that require male participation, the ring is discreet and female-initiated. Therefore, women can use the product without necessarily having to rely on their partner’s involvement. In particular, the ring expands the toolkit of HIV prevention options available to women who are unable to negotiate with their male partners to use condoms and remain faithful, or for those who are married, want to have children or are at risk of violence.

The monthly ring provides a long-acting alternative to other microbicide formulations being studied that are designed to be taken daily or around the time of sex. Women need more than one HIV prevention option, so they can choose according to their individual needs and preferences.
AVFTC: The FDA pushed back its approval of Truvada to be used in the prevention of HIV. To what extent does the approval of Truvada have an impact on the eventual approval of IPM’s ring?
Z: The FDA’s approval of Truvada as a pre-exposure prophylaxis against HIV could establish an important precedent for the approval of other ARV-based HIV prevention methods, including IPM’s ring.

Ultimately, regardless of whether the FDA approves Truvada, the dapivirine ring is primed for licensure. If the package of trials in the broader ring licensure program finds the ring to be effective and safe for long-term use, IPM will seek regulatory approval for the product, and collaborate with key partners to ensure that it is accessible and affordable to women in developing countries, where the need is greatest, as soon as possible.