GLOBAL INVESTMENT IN HIV CURE RESEARCH AND DEVELOPMENT IN 2017 AFTER YEARS OF RAPID GROWTH FUNDING INCREASES SLOW

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GLOBAL INVESTMENT IN HIV CURE RESEARCH AND DEVELOPMENT IN 2017 AFTER YEARS OF RAPID GROWTH FUNDING INCREASES SLOW TOWARDS AN CURE PEOPLE FOCUSED SCIENCE DRIVEN JULY 2018

A GLOBAL STRATEGIC APPROACH TOWARDS AN HIV CURE Antiretroviral treatment (ART) has radically changed the face of HIV infection, from a lethal disease into a manageable chronic condition. All 37 million people currently living with HIV are eligible for ART based on the 2015 WHO Guidelines for ARVs for treatment and prevention yet the latest data from July 2017 shows that only 20.9 million of these individuals are currently accessing ART. At the same time, daily antiretroviral regimens are costly and sometimes difficult for patients and most importantly not curative. HIV persists despite even the best treatment, and contributes to the development of non-aids morbidity. As such, it is time to sustain our investments in the search for an HIV cure or remission. Over the last decade, our understanding and knowledge of the mechanisms of HIV persistence and latent viral reservoirs has greatly improved. Many members of the scientific community now agree that the search for a functional cure or remission for HIV/AIDS may be within reach. Indeed, the past year has seen important new developments and continued progress in the areas of cure and remission research: Sustained periods of viremia control in the absence of therapy in adults receiving very early initiated ART. New research into tools to quantify replicationcompetent virus. New data on latency reversing agents in different populations and immunologic settings. Ongoing and new studies on the effect of ART treatment in acute infection on HIV reservoirs and virologic control in adults and infants. New research in humans of a toll like receptor TLR7- agonist in reducing latent virus. Advances in using CRISPR technology to create HIV immunity in cells. Continued progress in understanding how broadly neutralizing antibodies could be used alone, or in combination approaches, to HIV cure. Advances in understanding how to utilize the innate immune systems of people living with HIV. Early NHP data on HIV suppression through a block and lock strategy. To ensure effective future outcomes for cure research, the International AIDS Society s (IAS) Global Scientific Strategy: Towards an HIV Cure (2016) supports the establishment of an international multi-disciplinary research alliance and global coordination of existing consortia towards an HIV cure. It also provides a strategic analysis of the state of research in the area of HIV persistence and eradication in order to develop recommendations for future studies and to promote international and cross-disciplinary research cooperation. 16 M Treatment gap based on 2015 WHO guidelines The IAS Global Scientific Strategy: Towards an HIV Cure (2016), identifies the following scientific focal areas: Molecular biology of HIV latency and reversal strategies; Viral reservoirs, immunology of HIV persistence and kill strategies; Models for HIV cure or sustainable remission; Paediatric HIV cure; Gene and cell therapy; TREATMENT 37 M 21 M Total people on ART in 2016 People eligible for HIV treatment based on 2015 WHO guidelines Novel biomarkers and technologies to quantify and analyse HIV reservoirs; Social sciences and health system research. Increased investments in these areas will aid in the search for an HIV cure, but can also contribute to increased knowledge of HIV pathogenesis and control, advances in the HIV vaccine field and benefit public health globally, such as finding innovative treatments for people with cancer, Alzheimer s disease, other infectious diseases, and immune disorders.

Investment in Cure Research: 2017 shows sustained HIV cure funding In 2013, the IAS HIV Cure resource tracking group joined forces with AVAC to estimate global investments in HIV cure research. To date, this collaboration has yielded six years of estimates for cure research investment from 2012 to 2017. The Working Group estimates that in 2017, US$288.8 million was invested in cure research, representing an 8% increase over the US$268 million invested in 2016, and an increase of 228% over the US$88.1 million invested in 2012. The majority of investments (US$272.4 million) came from the public sector with US$16.3 million invested by philanthropies such as Aidsfonds, amfar, the Bill and Melinda Gates Foundation, CANFAR, the Campbell Foundation, the Fair Foundation and Sidaction. Despite outreach by the Working Group this year, few companies responded to the survey, whilst several companies are known to have active cure research programmes, resulting in a signficant underestimation for commercial investment in cure research. HIV Cure R&D Investments by Country, 2012-2017 Country 2012 2013 2014 2015 2016 2017 Australia 2.6 1.6 3.1 1.0 0.7 Canada 0.4 2.9 3.2 3.3 3.8 3.5 Cuba 0 0 0 0 0 European Commission 1.6 4.2 6.7 3.8 4.5 2.0 France 3.5 6.8 5.2 3.9 2.3 3.9 Germany 0 0 0 0 0.7 0.3 Italy 0 0 0 0 0 1.4 Sweden 0 0 0 0 0.6 0.6 Switzerland 0.03 2.0 2.3 2.1 The Netherlands 0 0 0 0 1.0 United Kingdom 0.03 0.03 1.0 4.3 1.3 1.4 United States 79.4 85.9 120.4 183.2 252.1 273.6 US$ Millions 300 250 200 150 100 50 7 6 5 4 3 2 1 0 2012 2013 2014 2015 2016 2017

Investments in HIV Cure R&D by Funder, 2015-2017 (US$ millions) 2015 2016 2017 164.4 NIH 229.7 255 0 50 100 150 200 250 US$ MILLIONS AIDS Fonds 1.0 amfar (with Fair Foundation) ANRS Bill & Melinda Gates Foundation California Institute for Regenerative Medicine Campbell Foundation 0.8 Canadian Foundation for AIDS Research (CANFAR) 0.009 0.008 Center for Genetic Engineering and Biotechnology Canadian Institutes of Health Research (CIHR) 2.3 3.7 3.1 2.9 2.9 3.2 4.2 3.9 5.8 7.1 7.0 7.1 7.6 7.0 6.8 Centre Hospital Universities Sainte-Justine 0.01 European Commission (EC) German Federal Ministry of Education and Research 0.7 0.3 Government of France 0.07 NHMRC 0.3 0.8 National Health and Medical Research Council 0.7 Sidaction 0.1 Sumagen Canada 0.08 0.9 Swiss National Science Foundation (SNSF) UK Medical Research Council (MRC) US Centers for Disease Control and Prevention 0.4 US Military HIV Research Program 0.1 1.3 1.4 1.7 2.0 2.1 1.9 3.8 4.5 0 2 4 6 8 10 12 14 US$ MILLIONS

In 2017, the United States through the US National Institutes of Health contributed the majority of public funding, with France, Canada, the European Commission, Italy, the United Kingdom, Australia, the Netherlands, Switzerland, Germany and Cuba also being contributors to HIV cure research. Current Research Investment, 2012 2017 (US$ millions) The successful implementation of the Global Scientific Strategy plan will require improved international scientific collaborative research teams and institutions at the international level to ensure an optimal use of resources. Active initiatives include: IAS Towards an HIV cure initiative The revised IAS Global Scientific Strategy: Towards an HIV Cure 2016, published in Nature Medicine, was launched in Durban at the AIDS 2016 conference. Martin Delaney Collabratories The National Institutes of Health has awarded $30 million in annual funding among six research collaborations working to advance basic medical science toward an HIV cure. US$ MILLIONS 300 250 200 150 100 50 88.1 104.7 160.8 201.8 268.0 288.8 amfar Countdown to a Cure for AIDS amfar focuses investments aimed at finding the scientific underpinnings of a cure by 2020. 0 2012 2013 2014 2015 2016 2017 The inclusion of cure in the global response should not direct funding away from treatment, prevention and care programmes, or from biomedical research on HIV and its consequences, including vaccine and other prevention research. However, it is imperative that donors, governments and the AIDS community make a viable and sustained economic investment in HIV cure research. METHODOLOGY Data collection was undertaken by AVAC on behalf of the Resource Tracking for HIV Prevention R&D accessing public information and collecting information through direct appeals to funding agencies. Requests were made to the public, industry and philanthropic sector funders requesting information on cure research grants awarded in 2017 using the cure definition developed by the US National Institutes of Health s Office of AIDS Research. In early 2018, surveys were sent to several dozen potential cure research funders across the globe. Responses from funders may not be comparable due to subjective determinations of whether specific grants fall within the OAR definition of cure research. Some funders also decline to provide information, and some did not always provide grant specific detail. In reviewing responses, AVAC accepted funders determination that specific research programs or grants are within the OAR definition.

Investments in HIV Cure R&D by Country, 2014-2017 (US$ millions) US$ 160.8 million 2014 120.4 United States 6.7 5.2 3.2 3.1 2.3 1.0 0.4 0.36 0.16 0.018 European Union France Canada Australia Switzerland United Kingdom Cuba Spain Portugal India US$ 201.8 million 2015 182.2 United States 4.3 3.9 3.8 3.3 2.1 0.6 0.07 United Kingdom France European Union Canada Switzerland South Africa Australia Sweden US$ 268.0 million 2016 252.1 United States 4.5 European Union 3.8 Canada 2.3 France 1.3 United Kingdom 1.0 Australia 0.7 Germany 0.6 Sweden Switzerland 0.4 Norway 0.3 Denmark 0.3 Japan The Netherlands US$ 288.8 million 2017 273.6 United States 3.9 3.5 2.0 1.4 1.4 1.0 0.7 0.3 France Canada European Union United Kingdom Italy The Netherlands Australia Switzerland Cuba Germany ACKNOWLEDGEMENTS The IAS Towards an HIV Cure initiative would like to thank Resource Tracking for HIV Prevention R&D, for which AVAC acts as Secretariat, and also includes the International AIDS Vaccine Initiative (IAVI) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) as members.