TAG at 20: Early Campaigns
Reforming NIH AIDS Research, Boosting the Budget and Revitalizing the Basic Science of HIV Infection
Among the most exciting results of the new investment in basic science were the discovery in 199596 by several labs at the National Cancer Institute (NCI), NIAID, and Aaron Diamond, of the two cellular coreceptors that HIV uses to get into cells -- the CXCR4 (or X4) and CCR5 (or R5) receptors. Besides unlocking the cell to HIV along with its first receptor, CD4, these two molecules also unlocked a whole series of scientific mysteries long noted in the literature, such as why certain strains of HIV preferred to infect CD4 T cells while others infected macrophages, and led to the discovery and development of a whole new class of anti-HIV drugs, the CCR5 receptor blockers, the first to be approved of which was Pfizer's maraviroc (Selzentry) in 2007. The identification of CCR5 also provided the basic-science rationale for the bone-marrow transplant therapy in Timothy Brown, the only person to be cured of HIV infection to date.
These are some of the results of TAG's first years of activist efforts to reform AIDS research at the NIH, massively increase research funding, and turn the field back to fundamental basic science to better understand, so as to better control, how HIV causes disease.
Two decades later, treatments continue to improve, saving and prolonging the lives of millions of people around the world, preventing countless new infections, and bringing hope that the single documented case of an HIV cure can be replicated, while the ultimate objective of a cheap and widely accessible cure and vaccine remains elusive.
Despite the advent of HAART and its global rollout, we are far from the end of the pandemic. The same combination of smart advocacy, good science, and more money, which helped lead to the HAART breakthrough in the mid-1990s, is now needed to revitalize political leadership, increase research funding, and encourage a new generation of scientists to embark on the search for a cure and a vaccine, the two prerequisites for ending AIDS once and for all.
Just as in 1992, the current political situation is dire. Last year only 10% of all NIH grants submitted were funded -- meaning 90% of them were rejected. This is bad news for young scientists, some of whom are likely to leave research altogether. While last year President Obama called science and technology growth essential to America's future, this year he recommended a flat NIH budget for fiscal year 2013 -- a far cry from his original (2008) campaign promise to ensure that NIH funding would be doubled over the current decade. TAG recommends that the NIH as a whole, along with the AIDS research budget organized by OAR, increase by 15% per year, which would allow a doubling by 2020.
Similarly, while therapy continues to improve, scientists are at an impasse with efforts to discover a cure and a vaccine. High-risk and innovative science driven by a comprehensive and coordinated research agenda will be essential to making these goals into realities. Many of the tenets of Gonsalves's 1993 report remain central to AIDS research today -- as NIAID acknowledged in its recent funding opportunity announcement (FOA), "Targeting Persistent HIV Reservoirs (TaPHIR)," which is designed "to stimulate the development of innovative tools and strategies for curing HIV infection....Novel approaches are therefore sought to efficiently monitor and specifically target reservoirs of latently infected cells to facilitate the testing of strategies to cure HIV infection in vivo." The FOA specifically requires that "latently infected reservoir cells from HIV-positive individuals on optimized HAART should be used for validation studies whenever possible." (grants.nih.gov/grants/guide-pa-files/PAR-12-109.html.)
In addition, the FDA needs to be brought in early to participate in the discussions about how to optimally conduct cure-related clinical trials to ensure the proper balance of rigor, flexibility, ethics, safety, and ability to answer the questions. In 2011 TAG, along with amfAR, AIDS Policy Project, and Project Inform, held an international consultation to discuss how to advance this work. Recently, the FDA and NIH commissioned a high-level scientific working group to address these issues over the coming 18 months, to be coordinated by the Forum for Collaborative HIV Research.
Finally, the struggle for domestic and global treatment access remains daunting. In the United States, almost 4,000 people are on AIDS Drug Assistance Programs (ADAPs) waiting lists, and globally 8 to 10 million people will need antiretroviral therapy in the coming two years, while funding by the U.S. and others is being cut.
AIDS has not yet emerged as an issue in this presidential campaign. It needs to if we are to successfully engage the national leadership in the demanding the necessary work ahead to end AIDS.
In coming articles we will examine the serial disappointments of early combination-therapy trials in the early 1990s, the crisis of confidence that led TAG to call for more rigorous and longer-term trials to better define the clinical utility of the next generation of HIV drugs -- the protease inhibitors -- as well as TAG's work on HIV-associated opportunistic infections and cancers, and the unexpectedly electrifying, medically revolutionary results of the combination of triple antiretroviral therapy, the clinical use of quantitative viral-load tests, and the advent of HAART in 1996, whose use is still being refined, optimized, and in the meantime rolled out to almost seven million people around the world.
This article was provided by Treatment Action Group. It is a part of the publication TAGline.
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