Breakthroughs Blog: Guest post

Research!America, a member of the GHTC, recently conducted analyses across a select group of target states to measure the health and economic impact of global health research and development (R&D), highlighting its benefits for states across the nation and strengthening the evidence base for Congress' support of federal investments in global health R&D. Danielle Doughman, Program Manager, Global Health R&D Advocacy, wrote this blog post to share the organization’s findings in the state of California. This post is the first of a series in which Research!America will continue to profile various states from around the country. Global health research not only has the potential to save lives and prevent disabilities, it is good business. And Californians agree. A clear majority—58%—agree that global health research is important to the state’s economy, and 70% agree that Americans would be better off if the United States invests in global health research. The need for better drugs, vaccines, and diagnostics for diseases that disproportionately affect the poorest and most vulnerable—about one in six people around the world—has been well-documented on this blog. The diseases include ones we’ve all heard of, like HIV and AIDS, but also killers that receive less attention, such as pneumonia and diarrhea. As part of our examination into what the United States is doing to advance global health R&D and why our continued support of such work is crucial for the health and prosperity of our future, we will examine six US state case studies, starting with California. California’s world class universities, businesses, and nonprofits create a robust global health sector with significant impacts on job creation, tax revenue and health. 70% of Californians agree that Americans would be better off if the United States invests in global health research. Photo: Evelyn Hockstein/PATH In 2010, the state received $3.3 billion from the National Institutes of Health, the world’s largest funder of global health research, supporting more than 62,000 high-quality jobs in the state. Overall, the global health sector supported 350,000 jobs in California with $19.7 billion in wages in 2007, the most recent year for which data are available. There are many, many public, private, academic, and philanthropic partners doing notable work in California and fostering productive collaborations across the United States and around the world. Here are just two examples: The International AIDS Vaccine Initiative’s Neutralizing Antibodies Center in La Jolla experienced recent breakthroughs that could play a major role in ending the HIV pandemic. The discovery of powerful, broadly-neutralizing antibodies have significant implications for AIDS vaccine design. What’s more, the same strategies may be applied to the development of a universal flu vaccine, potentially eliminating the need for annual flu vaccinations. Between 1976 and 2006, estimates of flu-associated deaths in the United States range from a low of about 3,000 to a high of about 49,000 people, so a universal flu vaccine would help save lives here in the United States and around the world. Malaria kills 650,000 people each year and results in $12 billion in endemic countries' lost gross domestic product annually. An affordable treatment means more children live, attend school, and can contribute to society. South San Francisco’s OneWorld Health, the first non-profit pharmaceutical company in the United States, works on drug development for malaria and other diseases of the developing world. Just last year, Sanofi, in partnership with OneWorld, began production of semisynthetic artemisinin, a breakthrough compound that makes effective malaria treatment much more affordable for the 200 million people—mostly kids—who contract it each year. The drug was developed at OneWorld with funding from the Bill & Melinda Gates Foundation.

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.

Kevin Fisher is the Policy Director for GHTC member AVAC: Global Advocacy for HIV Prevention, an organization that focuses on accelerating the development and delivery of critical AIDS vaccines and HIV treatment and prevention tools. AVAC and partners are hosting a congressional briefing this week to discuss promising results from a Military HIV Research Program’s (MHRP)-sponsored trial to develop a safe and effective HIV vaccine. Although further research is needed, a safe and effective HIV preventive vaccine has now been shown to be possible. In 2009, the Military HIV Research Program’s (MHRP)-sponsored RV144 trial became the first HIV vaccine trial ever to demonstrate effectiveness in preventing HIV infection, lowering the rate of HIV infection by 31.2 percent. MHRP, along with the study partners, announced another significant discovery in September 2011. Aiming to better understand how RV144 protects against HIV infection, the research team found two important molecular clues—two antibodies whose presence either increases or decreases the risk of HIV infection. With these findings, we are the closest we have come to discovering a scientific pathway to an HIV vaccine after three decades of research. The MHRP plans to evaluate the clues they discovered with follow-up studies. However, lack of funding for the MHRP may prohibit the researchers from advancing as planned. New findings show that we are the closest we have come to discovering a scientific pathway to an HIV vaccine after three decades of research. Photo: Satvir Malhotra/PATH Since 1986, the MHRP has worked to develop a safe, globally effective HIV vaccine and began providing critical support for the President’s Emergency Plan for AIDS Relief (PEPFAR) programs in Africa in 2004. Vaccines are one of the most powerful tools for preventing infectious diseases and should be one of the highest priorities of the research and scientific community to prevent the spread of HIV. While the unique properties of the HIV virus make finding a safe and effective vaccine one of the greatest challenges in science today, the MHRP has made extraordinary strides in meeting this challenge. MHRP is also a critical PEPFAR partner. While its primary focus is developing a globally effective HIV vaccine, the program provides prevention, care, and treatment through PEFFAR. With five sites in Africa and Asia, MHRP leverages existing in-country technical expertise and administrative infrastructure to expand partnerships with local researchers, health care services and NGOs to implement PEPFAR activities. Just as we are on the brink of a major breakthrough in HIV prevention the world is facing a global AIDS funding crisis. HIV treatment funding shortages and continued infection rates threaten to overtake progress made in the previous decade. The US has a critical role to play in stopping the spread of the epidemic, and through such programs as the MHRP the US can dramatically advance science and move forward the development of a safe and efficacious vaccine to control and halt the spread of HIV. As Secretary of State Hillary Clinton recently said, “An AIDS-free generation would be one of the greatest gifts the United States could give to our collective future.” On December 9th AVAC: Global Advocacy for HIV Prevention, amfAR, the Foundation for AIDS Research and the Infectious Disease Society of America, in cooperation with Sen. Barbara Mikulski, will be holding a congressional briefing focused on the work of MHRP. Join us to discuss the recent exciting and promising results from the MHRP scientific team and critical efforts to increase the impact of the PEPFAR program by delivering lifesaving drugs and prevention tools more effectively. Speakers will include: Dr. Debbi Birx (Centers for Disease Control and Prevention), Dr. Alan Fix (National Institute for Allergy and Infectious Diseases), Col. Nelson Michaels (MHRP) and Dr. Fred Sawe (Walter Reed Army Institute of Research–PEPFAR program, Kenya). Innovations in HIV Vaccine Development and PEPFAR Implementation through the Military HIV Research Program Friday, December 9, 2011 12:00-1:30 p.m. 385 Russell Senate Office Building SR-385 Lunch will be provided For more information or to RSVP, please contact Emily Donaldson at AVAC at edonaldson@avac.org.

Roger I. Glass, M.D., Ph.D., is director of the Fogarty International Center at the National Institutes of Health (NIH), where he oversees research and research training programs for U.S. and foreign scientists working to improve health in the developing world. Over the last four decades, about 5,000 scientists worldwide have received significant training through Fogarty programs. In addition, Dr. Glass serves as Associate Director for Global Health to the NIH Director, providing guidance on global health, facilitating international research collaborations and convening the world’s best scientific minds to address the most pressing health research questions. As we commemorate World AIDS Day 2011, I am both encouraged by the recent discoveries that are improving and prolonging lives and reminded of the challenges that remain in our battle to defeat this terrible disease. I was heartened to gather earlier this year with many of Africa’s premier infectious disease scientists and medical educators as we—together with PEPFAR—launched our Medical Education Partnership Initiative. Through this effort, we hope to make an enduring impact on the quality and availability of health care workers and researchers throughout the continent. This is vital to our goal to establish true country ownership and enable Africans to set their own research agendas, based on the most pressing local needs. Peruvian scientist Dr. Isaac Alva, of Universidad Peruana Cayetano Heredia, has conducted extensive field work studying HIV and AIDS and other diseases among indigenous communities in Peru. He is currently earning his master’s in public health through Fogarty’s AIDS International Training and Research Program. (Photo by David Snyder for Fogarty/NIH) I was also fortunate to see firsthand many of the researchers funded by the National Institutes of Health who are working on the front lines. During this year—the 30th anniversary of the beginning of this epidemic—it is appropriate we acknowledge the advances made against this and other infectious diseases by the National Institute of Allergy and Infectious Diseases (NIAID) and its director, Dr. Anthony S. Fauci, and by the many scientists around the world supported by NIAID and other institutes and centers of the NIH. But if the great advances have been made standing on the shoulders of giants, in Isaac Newton's phrase, I think Fogarty has a hand—or a shoulder, perhaps—in a number of the research breakthroughs. Trainees supported through Fogarty-funded grants have helped contribute to the work that led to this progress. We're pleased to see our 20-year investment in some of these developing country sites paying off with trainees who are well qualified to move forward the research funded by NIAID and others. A singular breakthrough in the news is the study known as HPTN 052, which revealed that men and women infected with HIV reduced the risk of transmitting the virus to their sexual partners through early initiation of oral antiretroviral therapy (ART). Fogarty grantee Dr. Myron "Mike" Cohen, who runs the global health institute at the University of North Carolina, is the principal investigator of the study, funded mainly by NIAID with additional funding from other institutes. Dr. Roger I. Glass, director of Fogarty International Center at the National Institutes of Health, visited Africa to see firsthand the health improvements HIV and AIDS advances have brought to the continent. (Photo courtesy of Fogarty/NIH) This is the first randomized trial to definitively indicate that an HIV-infected individual can reduce sexual transmission of HIV to an uninfected partner by beginning ART sooner. This adds very strong scientific evidence that you can use treatment of HIV as an effective prevention modality by decreasing the possibility that a person who is infected would transmit HIV to their sexual partner. More than 30 Fogarty-supported trainees in Malawi, India, Botswana and Thailand worked on the study. Very recently, the conclusions of this discordant couples trial were buttressed by results from a pre-exposure prophylaxis, or PrEP, trial that showed that heterosexual participants who took a daily Truvada pill had a significantly lower chance of being infected. Fogarty trainees are also at the forefront of the studies to determine the effectiveness of an antiretroviral microbicide (tenofovir gel) in preventing sexually transmitted HIV infection in women. The training was supported by a grant under Fogarty's AIDS International Training and Research Program (AITRP). Dr. Quarraisha Abdol Karim of Columbia University, who directed the CAPRISA-004 study, is the director of the Fogarty training grant and has mentored many trainees continuing this work. Moreover, Fogarty Scholar Dr. Kogie Naidoo has reported a randomized clinical trial conducted at Durban demonstrated that antiretroviral treatment should begin at the same time as TB treatment. This result has caused the WHO to change its guidelines for TB treatment. Finally, Dr. Sten Vermund of Vanderbilt University has directed a multi-country study, funded partly by NIAID with some Fogarty trainees participating, demonstrating the effectiveness of ART therapies in stopping mother-to-child transmission of the HIV virus. Sten's program has trained 64 individuals in degree programs, nearly all of whom have returned to their home countries. There remains much to be done in the effort to achieve "a world without AIDS," in Dr. Fauci's phrase. As we mark World AIDS Day and the 30th anniversary of that effort, Fogarty is pleased to have played a significant role in training many of the researchers who are positioned to lead the battle.