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Nelson L. Michael, M.D., Ph.D is the Director of the U.S. Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research (WRAIR), an international HIV vaccine research program that successfully integrates HIV and AIDS prevention, care and treatment. In this post, Col. Michael reflects on the progress being made in HIV prevention science. December 1 marks the commemoration of World AIDS Day—a day to reflect on an epidemic that has affected millions of lives worldwide for three decades now and how far we’ve come towards an end. This year’s focus and theme is a right on target: “Leading with Science, United for Action.” Recent scientific achievements have brought us closer to eliminating AIDS than we have ever been. Results from the landmark RV144 trial, an international collaboration that involved more than 16,000 Thai volunteers, were announced in 2009. While it took a quarter of the century from the discovery of HIV to show that a vaccine is possible, the results of RV144—which showed the first scientific evidence of vaccine efficacy—have propelled the HIV vaccine research field forward. Earlier this year, we announced the results of extensive follow-up laboratory studies that provide new clues about the types of immune responses that may have played a role in the protection seen in RV144. These new advances were the result of nearly two years of work by more than 100 researchers at 25 institutions worldwide. We now have a better understanding of how the vaccine may have prevented infection and a renewed scientific direction to help guide future vaccine development. We are united in our efforts to end AIDS; no one organization can do it alone. As we move forward, MHRP’s collaborators are leading a tremendous effort to identify correlates of protection. Additionally, a new collaboration—a public-private partnership called P5 that comprises MHRP, the Division of AIDS/NIAID, the Bill and Melinda Gates Foundation, Sanofi Pasteur, Novartis, and the HIV Vaccine Trials Network—is planning the next set of Phase IIb trials to build on the results of RV144 and bring us closer to a vaccine product with a public health impact. MHRP’s commitment to ending AIDS extends beyond developing an efficacious vaccine to creating innovative programs to prevent and treat HIV through the President’s Emergency Plan for AIDS Relief (PEPFAR). In 2011, our site in Uganda, the Makerere University Walter Reed Program launched the first ever mobile circumcision clinic with the ambitious goal to circumcise 6,000 men by year’s end, Kenya has become a leader in the prevention of mother-to-child transmission (PMTCT) due in large part to the efforts of the Walter Reed Project, and the number of patients currently receiving antiretroviral therapy at all of MHRP’s African sites—Kenya, Nigeria, Tanzania and Uganda—exceeded 100,000. A world without AIDS seems more achievable now than any other time in history. However, one prevention strategy alone will not be the end all to this pandemic. We must maintain the momentum and commitment to both scaling up currently available and evidence-based prevention strategies and finding a long-term solution to eliminate AIDS. In the meantime, MHRP is uniquely positioned to move HIV vaccine science forward and to inform HIV prevention, care and treatment with scientific data to develop best practices and to ensure the best, most efficient practices are provided around the globe.

Aarthi Rao is a senior program associate at the Center for Global Health R&D Policy Assessment of the Results for Development Institute. The Center analyzes a range of policy and financing ideas to accelerate the development of drugs, vaccines, and diagnostics for diseases of the poor. Ms. Rao works across many of its initiatives, including the assessment of tax credits for global health R&D and a study of the innovation system in India. This post shares some of the main findings of the Center's recent report, "R&D Tax Credits: A Tool to Advance Global Health Technologies?" As policymakers scramble to assemble measures that strengthen the US economy, tax credits are often proposed as tools to support domestic industry, spur job growth and encourage innovation with minimal intervention. In a political climate where the global health community worries about shrinking budgets and delivering “value for money,” tax credits to US companies to develop drugs, vaccines, and diagnostics for diseases of the poor seem even more appealing. While most policymakers agree that well-designed, tax credits are a good broad-based measure to support commercial R&D, making them work for global health is more complicated. Government support for R&D is often justified on grounds that the knowledge that R&D creates is a public good—by increasing overall knowledge, because innovation leads to improvements in general well-being. Nevertheless, firms would pursue a certain amount R&D on commercial grounds alone in order to earn profits from their innovations. But because R&D is high risk and costly, policymakers use tools, such as tax credits, to stimulate commercial innovation by lowering the costs and risks. The tricky part for the government is setting the right level for a tax credit—ideally, the government should offer credits that are high enough to encourage new innovation without paying for too much R&D that would have happened anyway. For biotechs and pharmaceutical companies doing global health work, tax credits may help offset some of their expenses, but the resulting technologies are unlikely to be profitable in the absence of other incentives since poor patients and countries have limited buying power. A reduction in losses can certainly help companies who are conducting global health R&D out of goodwill, but it will not likely catalyze much new research on its own. The UK, for instance, tried subsidizing research for HIV and AIDS, tuberculosis (TB) and malaria through a 20%-40% tax credit, but the private sector response was underwhelming. One solution is to increase the level of the credit and see if more firms respond, but this risks paying for a large amount of undefined work, much of which will fail in the early stages. However, there may be other ways to position a tax credit so that it does help to accelerate the development of new neglected disease technologies by US firms. There are new tax credit proposals on the table that challenge us to think past single mechanisms to packages of support that foster innovation. The Innovate America Act not only broadens the research tax credit, but it also suggests creating a pilot program to fund the commercialization of technologies developed through the National Science Foundation and mandates the development of a virtual platform for product developers to connect with public researchers. The Qualifying Therapeutic Discovery Project Tax Credit Extension Act reinforces the program’s focus on grants to emerging biotechs. These bills underscore that tax credits alone are not enough, and bring renewed attention to the challenge of commercialization. A tax credit for global health might encourage companies to do more early stage work, but they are unlikely to take on the full late stage development costs (think of the price tags for phase I-III clinical trials) for promising discoveries. Rather than pushing tax credit rates past 100%, a “package” approach could bring the most cost effective mechanisms for particular stages of R&D together. The ideas in the new tax credit legislation might not be quite right for global health R&D, but it is important that the global health community comes together to identify the ones that are. Discussions around product development for global health often focus on the role of product development partnerships (PDPs), or philanthropy on the part of industry and international donors—all of these are critical to global health—but there may be a way to make R&D for some diseases of the poor fit into the business models of US companies. Truly neglected diseases with almost no markets are unlikely to interest firms, but there are some neglected diseases that affect more than just the poor. Type II diseases, which have both donor and modest private sector markets, offer a good testing ground for incentive packages. For example, could a tax credit coupled with a purchase commitment shift the cost and risk equation far enough that firms could dedicate some of their brightest scientists to fighting diseases like dengue and TB? The tax credit could help offset upfront costs, whereas the purchase commitment helps ensure that a technology does in fact get fully developed by guaranteeing a certain level of market demand. This combination is just one possibility, but opens up a range of questions about what diseases have modest markets and what incentives suit particular stages of R&D. If these questions can be systematically laid out in relation to the preferences and strengths of US firms, then putting forward a well-designed package of targeted policies and incentives could be one way that global health advocates can advance the neglected disease pipeline by channeling bipartisan enthusiasm for supporting innovation in the US. To learn more about tax credits for global health R&D, read “R&D Tax Credits: A tool to Advance Global Health Technologies?”

Elena Pantjushenko is a communications associate for GHTC member OneWorld Health (OWH). She wrote this blog post to share the news of a major consortium project launched to boost elimination strategies for Visceral Leishmaniasis (VL, also known as kala-azar or black fever) in India and Bangladesh, where the disease burden is the world’s highest. The international consortium is led by another GHTC member, the Drugs for Neglected Diseases initiative (DNDi), together with OWH and the Special Programme for Research and Training in Tropical Diseases (TDR). A comprehensive four-year project to boost kala-azar elimination strategies in India and Bangladesh, where the concentration of disease burden is among the world's highest, was launched by an international consortium formed last month to support the countries' control and elimination strategies. The project aims to introduce the most effective treatment modalities to support control and elimination programs for this deadly disease. About Kala-Azar Kala-azar (VL) is a potentially fatal infectious disease that is transmitted through the bite of a sandfly and affects the visceral organs (e.g., enlargement of spleen and liver), causing chronic fever, weight loss and anemia. VL is endemic in 65 countries, primarily in the developing world, and the population at risk is estimated at 200 million. The disease often strikes impoverished populations living in rural villages who may not be able to afford the treatments currently available. If left untreated, VL is nearly always fatal. OneWorld Health developed Paromomycin Intramuscular Injection (PMIM) as an effective, inexpensive and safe treatment for VL, and worked with the Indian Government and Indian pharmaceutical company Gland Pharma to manufacture and distribute the treatment. PMIM received regulatory approval by the Drug Controller General in India, was designated for the WHO’s Model List of Essential Medicines, and was included in Essential Drug Lists of Nepal and Bangladesh. Collaboration Project Led by the Drugs for Neglected Diseases Initiative (DNDi), in collaboration with OneWorld Health (OWH), and the Special Programme for Research Training in Tropical Diseases (TDR), the project aims at establishing and implementing new treatment modalities as successful tools to control and support the elimination of VL in most endemic regions of South Asia. This four-year international consortium, established in October 2011, will generate the data necessary for Indian and Bangladeshi Ministries of Health to select, adopt and implement the best case management strategies to boost control and elimination of this deadly disease. OneWorld Health’s Role OneWorld Health will investigate the rationale for use of combination therapies with miltefosine, paromomycin and AmBisome® in the private sector in India as tools to control and support the elimination of VL. Project activities include pilot implementation of VL combination treatments at selected private sector clinics in India (target: 2,500 patients). In addition to development of the combination kits, this will include: working on drug inventory management and supply; site selection; site initiation (practicum and training); tracking of patients for compliance and pharmacovigilance; establishing adequate safe waste disposal methods; and establishing passive disease surveillance by the end of the project period. After completing the study, a feasibility report will be published. It will include recommendations for the private sector engagement in using new treatment modalities. Listen to Podcast

In a recent guest post for the ONE blog, GHTC director Kaitlin Christenson highlighted four game-changing HIV and AIDS interventions under development and the leadership from the US government that has helped foster these critical research breakthroughs. The fight against HIV and AIDS is not over, and a concerted effort must be made to prioritize research to develop new tools Photo: Robin Biellik/PATH The past three years have been historic in the number of breakthroughs in research to prevent, diagnose, and treat HIV and AIDS. For the first time, researchers proved that an HIV vaccine could prevent infection; an HIV prevention gel called a microbicide was shown to prevent infection among women; studies showed that a once-daily pill could reduce the risk of infection in high-risk individuals; and antiretroviral treatment among HIV-positive individuals was proven to reduce the risk of infecting their partners. "The fight against HIV and AIDS is not over, and a concerted effort must be made to prioritize research to develop new tools." Photo: Robin Biellik/PATHIt’s been incredible to see such progress over the past three years. But to be clear: these breakthroughs are a result of a long-standing commitment by international donors to boost research for HIV and AIDS. Innovations like these come as a result of years of work conducted by a variety of players—the private sector, NGOs, academic institutions and product development partnerships. In many cases, they are a direct result of the support provided by the US government. This commitment to research will continue to result in tools that change the way we approach the epidemic. Some impressive work is currently underway and promises to yield new interventions: Microbicides. Last year, a clinical trial in South Africa provided the first-ever proof that a vaginal microbicide could safely and effectively reduce the risk of HIV transmission to women. The trial was supported by the US Agency for International Development and two GHTC members, FHI360 and CONRAD. It provided new hope that an HIV-prevention tool designed for women could work. Additional research is needed on this product, though, and over the next two years, a follow-on trial will seek to confirm these results. Treatment as prevention. This summer, research supported by NIH demonstrated an astounding 96 percent reduction in transmission of HIV to an uninfected partner when his or her HIV-infected partner begins an antiretroviral regimen. Some questions remain about how this intervention might be implemented, and additional research is needed to understand how treatment as prevention will be operationalized. Oral pre-exposure prophylaxis (PrEP). Recent studies funded by the US National Institutes of Health (NIH) and others have confirmed that a daily dose of oral antiretrovirals can reduce the threat of HIV infection in high-risk groups. While additional research is needed to understand the implications of PrEP, many government agencies are considering adapting their HIV prevention guidelines to account for this new intervention. HIV vaccines. Two years ago, a clinical trial conducted in Thailand and funded by the US Department of Defense provided the first demonstration that a vaccine can prevent HIV infection in humans. While the results from this trial were too modest to support licensing this particular vaccine, trial data will help to inform the development of what researchers hope will be a more effective vaccine. On a recent trip to Kenya, my colleagues and I had the opportunity to meet with some of the research heroes who are leading the way in studying these and other interventions. The excitement they felt about the promise these new tools might provide was palpable. Lisa Mills, an American based with the CDC in Kenya, co-led a clinical trial which provided evidence for treatment as prevention. She told us that this intervention will have a “huge impact on communities. It will make HIV-positive people in these communities non-contagious. It’s also more cost-effective to do treatment as prevention, since you’re only treating HIV-positive people.” In speaking about research for microbicides, another of the individuals we met, Elizabeth Bukusi, deputy director at the Kenya Medical Research Institute (KEMRI), told us, “I think this is one of the tools that gives us the opportunity that we could actually end the epidemic. I think we can move towards a complete AIDS-free generation that will completely stop the epidemic in its track using microbicides as part of the armament.” She added that the “US has been a critical partner in providing catalystic funds and also in funding a large number of the trials that have looked at microbicides. So US funding is absolutely critical to moving this agenda forward.” Today, it is in our hands to decide the fate of future generations. The fight against HIV and AIDS is not over, and a concerted effort must be made to prioritize research to develop new tools — both those that are within arm’s reach, and those which still require much more study. Research is a long-term investment, and we must not give up on the commitments which have taken us this far. The US government is a leading supporter for research that has yielded many of the innovations we have today, and this support must not waiver even in the midst of today’s constrained budget environment. Will our leaders continue to set the stage? Imagine the breakthroughs that would be possible if so.