Breakthroughs Blog: Microbicides

In this guest post, Dr. Judy Manning from the US Agency for International Development (USAID) and Dr. Zeda Rosenberg from the International Partnership for Microbicides (IPM) discuss the need for new and improved contraceptive options for women worldwide. The post was written to mark World Contraception Day. The picture could not be clearer: A woman's health and livelihood are threatened when modern family planning methods are out of her reach. On World Contraception Day (September 26), we are reminded that unintended pregnancy is a major contributor to maternal and infant death and disability around the world, and a recognized obstacle to global development. Forty percent of pregnancies worldwide are unintended, but that number is not so surprising when you consider that 222 million women have an unmet need for modern contraceptive methods. Access to such methods would enable women to plan and space their pregnancies, leading to improved health, educational, and economic outcomes for themselves and their families. New sexual and reproductive health innovations have the potential to revolutionize women's options by diversifying delivery forms, varying product duration, and targeting multiple health risks simultaneously. Photo: PATH. According to the Guttmacher Institute, 70 percent of the unmet need stems from method-related concerns. These include concerns about the safety and potential side effects of hormonal methods; appropriate options for women who have infrequent sex, or who are postpartum or breastfeeding; and opposition from their partners to specific approaches. Geography and access to health services are also barriers to modern contraception. Last year at the London Summit on Family Planning, the global community made an unprecedented pledge to reach 120 million more women with contraception by 2020. The upcoming International Conference on Family Planning in Ethiopia will map out additional steps required to make contraception available for all women. Efforts will focus on expanding access to existing methods as well as prioritizing the development of new innovative technologies. New sexual and reproductive health innovations have the potential to revolutionize women's options by diversifying delivery forms, varying product duration, and targeting multiple health risks simultaneously. Unfortunately, there is no magic bullet. When it comes to sexual and reproductive health, women face obstacles that are unique to their circumstances. But experience has taught us that if women have a range of affordable and appropriate products to pick from, they may use them more consistently, which in turn will allow them to better protect their health. We are excited about a number of cutting-edge technologies now in development. For instance, USAID is investing in the early-stage development of a biodegradable contraceptive implant that does not require removal. This product from FHI 360 could fill a critical gap in low-resource settings where women may not have access to trained health workers. Alongside contraceptive-only products, multipurpose prevention technologies (MPTs) can help address women's overlapping health needs in a single product. For example, women in areas with high rates of HIV often have the greatest unmet need for family planning, creating a double burden of risk. With support from USAID and other funders, IPM is developing a 60-day MPT ring to offer dual protection against HIV and unintended pregnancy that women could use discreetly. The self-initiated ring is being designed to provide sustained release of an antiretroviral (ARV) drug called dapivirine along with the contraceptive hormone levonorgestrel. USAID and other funders also recognize that, in many regions of the world, sexually transmitted infections (STIs) such as herpes simplex virus, human papillomavirus, and bacterial vaginosis are of greater public health concern than HIV. As a result, USAID is supporting CONRAD (in partnership with PATH) to develop an MPT that combines the new one-size-fits-most SILCS diaphragm with tenofovir gel—the first ARV drug shown to help prevent both HIV and herpes (a confirmatory trial of tenofovir's effectiveness is under way). This could provide women with a non-hormonal product that could be used "on demand," appealing to women who would like a product that is used at the time of sex. MPTs could result in significant health gains for women by broadly addressing their sexual and reproductive health needs, and reducing rates of maternal and newborn death associated with both unintended pregnancy as well as STIs. In fact, there is reason to believe that MPTs may have another added benefit: Combining two or more products into one may make protection more appealing and acceptable to women, and therefore increase its use. To fully realize the immense promise of up-and-coming innovations, we need continued investment in the development pipeline and in full access to the final products. No single product will address every woman's sexual and reproductive health needs, so it will take a portfolio of methods to ensure that women have options to choose from that are appropriate for their individual circumstances. New tools are not developed overnight—they take time, effort, and dedicated resources. But it is an investment that will help make modern contraception a reality for the 222 million women whose lives, health, and development depend on it. Originally posted by the Policy Innovations blog, a publication of Carnegie Council.

On the second day of the XIX International AIDS Conference, the need for a host of new tools to prevent and treat HIV and AIDS has already made it to the forefront of the agenda. Of particular note has been the resounding call for a vaccine to prevent HIV, with leading policymakers, scientists, and advocates saying that the world will never reach the end of AIDS without this powerful tool. In a session that focused on improving the effectiveness and efficacy in the HIV and AIDS response, Senator Lindsey Graham (R-SC) said that a vaccine is desperately needed to help make a sizable dent in the pandemic. Graham’s call for a vaccine was echoed by Bill Gates from the Bill & Melinda Gates Foundation. The “ultimate tool” in the fight against HIV and AIDS “will be a vaccine,” Gates said, adding that the US government has been the largest supporter of efforts to develop and vaccine “by far.” He also said that microbicide gels and rings will be powerful prevention products. Without a number of these new tools, the world cannot “talk seriously about moving toward the end” of the pandemic. “We will get these tools, but only if we stay the course.” Later in the afternoon, National Institutes of Health (NIH) Director Francis Collins and Jon Cohen from Science magazine chaired a panel that looked at what lies ahead in HIV and AIDS science. Gary Nabel, director of the NIH’s Vaccine Research Center, said “we’ve never been in a more exciting position” in the search for an HIV and AIDS vaccine. He added that recent discoveries related to broadly neutralizing antibodies over the past two years have made HIV vaccine research “like a phoenix rising from the ashes.” When sharing their hopes for the status of HIV and AIDS research, several panelists also stressed the urgent need to develop new HIV prevention and treatment options. Nabel said that by 2020, he expects researchers will be “in the midst of efficacy trials for an HIV vaccine candidate.” Robert Siliciano of the Johns Hopkins University School of Medicine stressed that by 2020, scientists will be leading clinical trials for new drugs that attack HIV reservoirs. And Dawn Averitt-Bridge of the Well Project said that by 2020, she hopes the world has effective microbicides to prevent HIV, a functional cure for the disease, and that “research makes it into the lives of the people and families we all care so much about.” Cohen ended the session with a call for young people to become the “next generation of scientists” leading HIV and AIDS research. “I’m looking to the young people, because that’s where the revolution is going to happen.” Kim Lufkin is the GHTC’s communications officer.

Dr. Bríd Devlin is the executive vice president of product development of the International Partnership for Microbicides (IPM), a GHTC member. In this guest post, she writes about a new study IPM launched last week that will look at a new HIV prevention option for women. Last week, IPM announced The Ring Study, a Phase III efficacy trial to determine whether a monthly antiretroviral (ARV)-containing vaginal ring can safely and effectively help prevent HIV infection in women. This product could provide women with discreet, long-acting, and easy-to-use protection. In my role, I oversee IPM’s drug development projects. After working on a variety of drug delivery technologies for over 18 years, I cannot overstate how excited I am about a ring for prevention of HIV—this could be a real game-changer. The ring is a platform technology that has been used successfully for other medical purposes for decades. IPM has adapted the ring to potentially stem the spread of HIV to women in sub-Saharan Africa, the epicenter of the epidemic and where our studies show high acceptability for such a product. While highly effective, current HIV prevention options often cannot be used by women who are disproportionately vulnerable to infection. The ring is a promising way to expand women’s prevention options on multiple levels. First, several studies have shown that the same types of ARV drugs that successfully treat HIV may also protect against infection before it has a chance to take hold. In addition, by offering women sustained, monthly protection, it could overcome the burden of adherence, which is crucial to achieving the protective benefit offered by ARV-based prevention. As Sarah Boseley of The Guardian wrote in her recent blog, it’s a tool that “women can wear and forget about—at least for a month at a time.” The ring is also female-initiated and discreet. This means women can control their own HIV prevention without having to rely on a male partner’s cooperation or action. IPM has announced The Ring Study, a Phase III efficacy trial to determine whether a monthly antiretroviral (ARV)-containing vaginal ring can safely and effectively help prevent HIV infection in women. Additional studies in the field are looking at other approaches to female-initiated prevention, such as gels used around the time of sex and daily pills. It is important for women to have a range of options so that they can choose a product that best meets their needs and preferences. This year, IPM celebrates its 10th anniversary and a decade of progress in helping to advance HIV prevention for women. We have not arrived at this milestone alone. Partnership is at the core of our business model and mission. By working with partners across the public and private sectors, we amplify our individual resources and scientific ingenuity to help meet the health needs of women everywhere. For instance, the National Institutes of Health-funded Microbicide Trials Network will begin a larger Phase III “sister” study of the ring called ASPIRE in the coming months. Given its promise as a delivery mechanism, IPM is adapting the ring to meet the unique needs of women. With funding from the US Agency for International Development, we are developing a dual-purpose prevention ring designed to provide both HIV protection and contraception in a single product. We are bringing together global leaders to talk about the urgent need for multipurpose prevention technologies at Advancing the Integration of HIV and Sexual and Reproductive Health, a satellite session IPM is cohosting with Women Deliver at the upcoming International AIDS Society (IAS) conference. In late July, thousands of HIV scientists, policymakers, and activists will descend on Washington, DC, for the IAS conference. The theme is “turning the tide together” and one topic that will be highlighted is promising developments in HIV prevention. IPM looks forward to the ring being part of that conversation.

Luann Tia Blount is the Clinical Communications Officer for GHTC member the International Partnership for Microbicides (IPM), a nonprofit product development partnership dedicated to developing new HIV prevention technologies and making them available to women in developing countries. This post discusses novel approaches to HIV prevention, namely an adapted medical technology used to deliver hormones to women—the vaginal ring. Last week, in honor of World AIDS Day, the International Partnership for Microbicides (IPM) renewed its commitment to finding innovative ways to fight the spread of the epidemic. At the International Conference on Family Planning in Dakar, Senegal, IPM announced a five-year award with a $2 million ceiling from the US Agency for International Development (USAID) to support the development of a 60-day dual-purpose vaginal ring that would combine the antiretroviral (ARV) drug dapivirine with a contraceptive to offer women around the world both HIV protection and contraception in a single product. Research has consistently shown that a woman’s risk of HIV and her reproductive health are inherently linked, demonstrating a clear need for tools that women can use that address these issues in tandem. Filling the gap in maternal health services for women who want to delay or prevent pregnancy could decrease the number of women who die during pregnancy or childbirth by about one-third. Expanding women’s options with a discreet and affordable product that could safely meet both women’s contraceptive and HIV prevention needs could therefore help reduce maternal mortality and empower women to protect their own health. The USAID funding will support IPM as it integrates a contraceptive into IPM’s existing dapivirine-only HIV prevention ring, also in development. The dapivirine ring adapts a medical technology commonly used to deliver hormones to women—the vaginal ring—to the fight against HIV. Expanding women’s options with a discreet and affordable product that could safely meet both women’s contraceptive and HIV prevention needs could therefore help reduce maternal mortality and empower women to protect their own health. Photo: Andrew Loxely The dual-purpose dapivirine-contraceptive ring could one day offer a convenient and affordable option for women who cannot negotiate the use of condoms or for whom condoms are not always a realistic choice. In addition, because the ring offers sustained protection, it may help women use it consistently and could help ensure its effectiveness. Dapivirine is IPM’s most clinically advanced microbicide candidate. It belongs to a class of ARVs known as non-nucleoside reverse transcriptase inhibitors, or NNRTIs, which work by preventing HIV from replicating its genetic material after the virus enters a healthy cell. ARVs have long been used successfully to treat HIV and to prevent mother-to-child transmission, and research in the past year has shown their potential to prevent HIV. IPM is developing the drug for use as a microbicide through a royalty-free license granted by Tibotec Pharmaceuticals, one of the Janssen pharmaceutical companies. Since 2004, 15 clinical safety studies of dapivirine, formulated as either a vaginal gel or a vaginal ring, have been conducted by IPM and its partners showing that it is safe and well-tolerated by women. Early next year, IPM will advance a different product, the dapivirine-only HIV prevention ring, into a product licensure program with its partner, the National Institutes of Health-funded Microbicide Trials Network (MTN). The monthly dapivirine ring may also help expand women’s HIV prevention options with a long-acting and easy-to-use product women can use to protect themselves. As part of the program, IPM will conduct the Ring Study, also known as IPM 027, which will collect long-term safety and efficacy data and involve 1,650, healthy, HIV-negative women ages 18 to 60 at several research centers across Africa. The Ring Study will also assess women’s adherence to and acceptability of the vaginal ring. MTN will conduct a second efficacy study of the dapivirine ring next year. Called ASPIRE—A Study to Prevent Infection with a Ring for Extended Use, also known as MTN-020—the trial will enroll approximately 3,475 HIV-negative women between ages 18 and 45 in five African countries. Collectively, these two studies will provide the data necessary to determine dapivirine’s suitability for licensure, should the product prove effective. IPM is also exploring other novel approaches and combinations products such as a maraviroc ring and a maraviroc-dapivirine combination HIV prevention ring, also in partnership with MTN. Maraviroc is a CCR5 blocker that works by obstructing a receptor (CCR5) on the surface of cells that is used by the most commonly transmitted strains of HIV-1 to attach to and enter healthy cells. When that receptor is blocked, HIV cannot enter healthy cells. IPM is developing maraviroc for use as a microbicide through a royalty-free license with ViiV Healthcare. This is the first time maraviroc is being studied for use as a microbicide. As we know from the contraceptive field, a variety of product choices greatly increases the chances that one of them will be used. So our best weapon against the epidemic is a range of daily and long-acting options that meet women’s unique needs and preferences.