Breakthroughs Blog: Microbicides

Meet Grace, Denise, and Sarah. At age 21, Grace is a single mother of two living in South Africa. Because her children need routine check-ups and immunizations, Grace frequently sees pediatricians and nurses, but rarely visits doctors for her own health needs. In Namibia, 19-year-old Denise is a first-time mother. She wants contraceptives but the few times she’s asked, the local pharmacist said they were available only for married women. And in Malawi, 18-year-old Sarah has started having sex, sometimes with male partners twice her age.  These three young women lead very different lives, but they all have one thing in common—they’re at high risk for HIV infection. Although Grace, Denise, and Sarah are not real people, their stories illustrate diverse challenges young women face, particularly in sub-Saharan Africa, where young women ages 15-24 are at least twice as likely to have HIV as men their age—and, in some regions, are more than eight times as likely to get infected. IPM's Sharyn Tenn with workshop participantsExisting HIV prevention strategies are not doing enough to reduce the high rate of infection among women because women still lack a range of options that address their diverse needs. While some women may feel comfortable discussing available HIV prevention options such as condoms with their partners, negotiating safe sex is not a realistic option for many others, including those at risk of sexual violence. In addition, while some women may be able to use a daily oral HIV prevention pill known as PrEP, in the three African countries where it recently become available, others may prefer a long-acting prevention method.The payoff for all of these tools spans far beyond individual women—evidence shows that when women are both empowered and healthy, they are more likely to have healthy families, educate their children, and make positive social and economic contributions to society. New discreet and long-acting HIV prevention tools have the potential to empower women to protect their own health and unlock their potential.My organization, the International Partnership for Microbicides (IPM), has developed one such tool–the monthly dapivirine ring. This flexible, silicone vaginal ring is the first long-acting, self-initiated method shown to safely help prevent new HIV infections in women.Results from two Phase III clinical trials last year—The Ring Study and ASPIRE—found that the ring safely reduced HIV risk among women in four African countries. Data from one study suggests that women who used the ring most consistently saw greater risk reduction, and that the youngest women, who saw little to no protection, appeared to be the least likely to use the product. Such adherence challenges are consistent with studies of other HIV prevention methods and underscore the urgent need to identify and overcome barriers to product-use for young women. The dapivirine ring. (Photo: Andrew Loxley) IPM is committed to doing all we can to understand how to help young women who want to use new HIV prevention technologies, like the monthly dapivirine ring, to do so consistently. Last month, we, along with AVAC, the US Agency for International Development, and Dalberg Global Development Advisors, co-hosted an event during the United Nations Commission on the Status of Women to take a holistic view of young women’s lives. Presenters shared examples of the ways HIV-prevention efforts can be informed by the very people who would benefit leveraging an approach called human-centered design, which places end-users and other key stakeholders at the center of the design and implementation process. This approach is being used to create concepts and materials to increase the adoption and sustained use of the dapivirine ring.Several insights shared at the event could inform future steps for the dapivirine ring, should it be approved for use and added to HIV prevention programs in sub-Saharan Africa. For example, the ring could be offered where women already regularly access health services, whether for themselves or for their children.Doing so would make access to the ring more convenient, and subsequently, may increase its uptake. Participants also suggested that a welcoming, environment may also help facilitate uptake as fear of judgment can be a powerful barrier to accessing and using HIV prevention products and services.We’re encouraged by these discussions, recognizing that they are one step in a long and iterative process of getting new HIV-prevention methods into the hands of women worldwide. Continuing to involve women in additional research on the ring and its possible introduction must continue if we are to realize its potential and pave the way for other technologies in the pipeline such as a three-month dapivirine-only ring and a multipurpose dapivirine-contraceptive ring. We’re currently pursuing regulatory approval for the dapivirine ring and looking to two open-label extension studies—DREAM and HOPE—currently underway, to gain insight into when, why, and how women use the ring now that its safety and efficacy are known, and to collect extended safety data.Expanding the toolkit of HIV prevention options available to young women would lower HIV infection rates, allow healthy women to pursue employment, and help sustain strong and productive workforces.The sooner we reduce the heavy HIV burden young women bear, the sooner we can empower a new generation to lead healthy and productive lives. Sharyn Tenn is the senior director for external affairs at the International Partnership for Microbicides.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. For many years, ineffective treatment plans and archaic diagnostic tools have stood as a barrier to tackling tuberculosis (TB). More recently, new drugs and diagnostics have emerged. Yet, availability has not always translated to widespread access. For example, despite the availability of new rapid diagnostic tools like GeneXpert, it is estimated that over 40 percent of new TB cases go undiagnosed or are not reported and use of older, less accurate sputum tests still outpace use of the GeneXpert. Though new drugs like bedaquiline and delamanid are not available, more than 75 of patients who need them do not have adequate access. A number of hurdles to adoption and scale-up exist from lack of funding for TB programs to high costs to implementation failures Action is needed by global leaders and innovators to break down these barriers if the global community wants to achieve its goal of eradicating TB by 2030. Malaria is more complex than scientists previously thought. In a recent study published in the Proceedings of the National Academy of Sciences, scientists used DNA fingerprinting to track malaria on a cellular level. They found that the parasite has a heightened level of genetic recombination developed during meiosis, leading to a wide variety of malaria strains. This suggests that malaria can evade immune system response, acting as a chronic disease—and it means there is no one-cure-fits-all solution. Because of the incredible amount of genetic diversity malaria can have in the body, one vaccine solution may not work for all individuals, casting doubt on the efficay of vaccines now in development. While this discovery makes malaria harder to prevent and eradicate, scientists have also discovered that malaria isn’t as transmissible as it first seemed, with the parasite only causing five or six secondary cases from one original infection, whereas it was previously thought one case could subsequently infect dozens of individuals. The International Partnership for Microbicides (IPM) has announced a clinical trial that is hopeful to significantly reduce cases of HIV in Sub-Saharan Africa and around the world. The clinical trial will use the IPM-developed dapivirine ring, a small silicone ring inserted in the vagina, releasing a contraceptive (levonorgestrel) and an anti-HIV drug (dapivirine). The ring is easy to insert and lasts three months. Building on the previous ring that only released dapivirine, having the ring also act as a contraceptive will not only reduce the likelihood of HIV infecting women, but will also provide women with the choice to protect against unwanted pregnancy. This trial is especially important because women are most at-risk for contracting HIV, especially in countries with low rates of condom use. IPM hopes to have the ring ready for shipment globally by 2020.    

2016 was a year that ushered in significant shifts in the global health landscape. We witnessed the waning of the Ebola epidemic and the waxing of the Zika outbreak; important leadership changes among the biggest institutional players in global health; and the development and introduction of new innovations that could turn the tide against leading infectious disease killers. As the year comes to an end, GHTC is reflecting on the top stories in global health innovation that made news in 2016. Here are seven of those top moments: 1. Scientists mobilize against Zika A vial of the National Institute of Allergy and Infectious Diseases (NIAID) Zika Virus Investigational DNA Vaccine (Photo: NIAID).Once considered an obscure virus responsible for a mild illness, Zika took the world by storm in 2016. As the virus gained a foothold in more than 60 countries, its association with devastating birth defects and neurological conditions was firmly established. Prior to Zika’s emergence in the Americas, only 25 research papers had been published on the virus. As the epidemic grew, scientists around the world joined the fight against Zika, often sharing their data and research in real time to speed progress. Thanks to the efforts of these researchers, over the past year our scientific understanding of Zika has grown exponentially, and we have advanced a robust pipeline of new tools to prevent, detect, and treat Zika. Today, there are more than 35 Zika vaccine candidates under development; 13 Zika diagnostics have been authorized for use by the US Food and Drug Administration; and researchers are screening novel compounds and evaluating existing drugs to advance treatments for the disease. 2. The world commits to the fight against antimicrobial resistance United Nations General Assembly (Photo: GHTC/Matthew Robinson). 2016 marked the year the world finally got serious about tackling antimicrobial resistance. On the heels of several major analyses examining the potentially devastating health and economic impact of antimicrobial resistance, the United Nations (UN) General Assembly convened global leaders for a high-level summit on antimicrobial resistance—the fourth time such a meeting has been held on a health-related topic during the UN’s 71-year history. At the close of the summit, UN member states unanimously endorsed and adopted a political declaration committing to developing action plans and policies; mobilizing resources; and supporting public awareness, surveillance, and R&D efforts to combat antimicrobial resistance. It is our hope that 2017 will mark the year political commitment translates to concrete action to advance the development of new antibiotics. 3. New strategies deployed to stymie mosquito-borne diseases Mosquito-borne diseases remain an age-old scourge, but 2016 saw the advancement of several novel strategies to combat these tiny foes. Efforts to combat mosquito-borne diseases with the transmission blocking–bacteria Wolbachia took an important leap forward this year. Past studies have shown that when the Wolbachia bacteria is introduced to Aedes aegypti mosquitos—which carry viruses like Zika and yellow fever—it prevents the viruses from replicating and blocks further transmission. Because the bacteria can be passed from one generation of mosquitoes to the next, the bacteria offers hope for eliminating a virus’s presence within a local mosquito population. After several years of conducting small-scale tests of this method, the Eliminate Dengue Program announced in 2016 it would begin conducting two large-scale trials in South America to determine whether this approach is effective in halting the spread of mosquito-borne diseases in large urban settings. This year the biotech company Oxitec also advanced efforts to test the use of genetically modified mosquitoes to reduce mosquito populations and disease transmission. The company has engineered mosquitoes that mate with A. aegypti mosquitoes, producing offspring that are unable to mature to adulthood. Early last year, Oxitec introduced the mosquitoes into the Brazilian city of Piracicaba, resulting in an 82 percent decrease in the population of A. aegypti mosquitoes in just nine months. Now, Oxitec has expanded the trial to a larger geographical area and is also initiating trials in the Florida Keys and the Cayman Islands. 4. World’s first kid-friendly TB medicine launches Children who receive tuberculosis (TB) medicines require a different dose than adults, yet until this year, there were no TB medicines designed specifically for children, so parents were forced to split or crush adult pills in an attempt to administer the right dose to their child. This year, that all changed with the launch of the world’s first kid-friendly TB medication. Developed by TB Alliance, the medicine is designed with the unique needs of children in mind: It is fruit-flavored, dissolvable in water, easy to administer, and appropriately-dosed. Already, more than 30 countries have adopted the new medicines, and enough orders have been placed to treat half of childhood TB cases worldwide. 5. Unique HIV prevention option for women reaches important development milestone Image captionMonthly vaginal dapivirine ring helps protect women against HIV (Photo: International Partnership for Microbicides). Women may soon have a powerful new tool at their disposal to prevent HIV infection. Earlier this year, the International Partnership for Microbicides (IPM) announced the results of two large phase 3 clinical trials demonstrating that a monthly vaginal ring containing the antiretroviral drug dapivirine can help protect women from HIV. While initial results indicated that the dapivirine ring reduced HIV risk by approximately 30 percent, further analysis revealed that the ring reduced infection rates by 75 percent in women who used the ring consistently. Now, IPM is seeking regulatory approval for the dapivirine ring and is conducting open-label studies, enabling trial participants to continue using the ring as IPM collects additional data. The dapivirine ring is the only long-acting, female-initiated HIV prevention tool to have proven successful in phase 3 clinical trials. Young women in sub-Saharan Africa are more than twice as likely to be infected with HIV than their male counterparts, and thus female-centered prevention tools are needed stem the epidemic. 6. Roll out begins of world’s first malaria vaccine candidate After decades of development and testing, the world’s first malaria vaccine candidate will soon be introduced in several communities in sub-Saharan Africa. The vaccine—RTS,S—was developed by PATH and GlaxoSmithKline and received a positive opinion from the European Medicines Agency last year following completion of phase 3 clinical trials. In November, the World Health Organization (WHO) announced it would pilot and evaluate the vaccine in real-life settings, thanks to funding from The Global Fund; UNITAID; and Gavi, the Vaccine Alliance. Pending results of these pilot tests, WHO will determine whether to deploy the vaccine on a wider scale. 7. New global health technologies advance through the pipeline PATH launches an easy-to-use, rapid diagnostic for onchocerciasis (Photo: PATH/Dunia Faulx) Over the past year, several other promising new health innovations have moved through the development pipeline and one step closer to reaching the hands of patients: Two important health tools—a novel, affordable oral cholera vaccine developed by the International Vaccine Institute, and the Woman’s Condom developed by PATH and partners—received WHO prequalification this year, paving the way for their procurement by UN agencies and other international procurement organizations. Two new rapid diagnostic tests for the neglected tropical diseases onchocerciasis (river blindness) and lymphatic filariasis were launched this year. Developed by PATH, these tests provide results in just 30 minutes and can be stored at a wide range of temperatures. Development has begun for an affordable therapy for hepatitis C. In 2013, the world’s first cures for hepatitis C hit the US market, however, treatment remains out of reach for many patients due to the high price tag. This year, the Drugs for Neglected Diseases initiative announced it would begin testing an alternative therapy in phase 2 and 3 clinical trials, with a guarantee from the manufacturer that, if successful, the entire regimen will be sold for no more than US$294.  As 2016 draws to a close and 2017 begins, it is time for the global health community to redouble our efforts to make sure this vital progress in global health innovation continues to ensure that people around the world will have access to lifesaving and life-improving health technologies.

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC