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TAG’s Involvement in HIV Cure Research

May 19, 2015

Achieving a cure has always been a central to TAG’s mission. The organization’s early advocacy included stressing the importance of basic science research, because there were many fundamental aspects of HIV biology and pathogenesis that needed to be understood in order to develop better treatments and, ultimately, a cure (see Basic Research on HIV Infection: A Report From the Front, by Gregg Gonsalves, 1993). Key issues identified at that time included the need to understand mechanisms of HIV persistence and “which cells and tissues serve as reservoirs for HIV.”

Research on individuals highly exposed to HIV, but uninfected, was also highlighted as a priority. In the early 1990s, TAG members requested that the National Institute of Allergy and Infectious Diseases (NIAID) convene a workshop on the subject, and funding for the work eventually led to the discovery of the HIV coreceptor CCR5 and the natural genetic variant—known as the CCR5Δ32 mutation—that can cause its absence, and thus confer resistance to most HIV strains. These discoveries made the design of CCR5 inhibitors possible, and are now making important contributions to cure research (receipt of a stem cell transplant from a donor with the CCR5Δ32 mutation appears to have played a key role in the case of the one individual considered cured of HIV infection, Timothy Brown).

When highly active antiretroviral therapy (HAART, now generally referred to as ART) became available in the mid-1990s, there were hopes that several years of complete HIV suppression might be sufficient to lead to clearance of all virus-infected cells. But efforts to identify HIV reservoirs revealed a population of latently infected memory CD4 T cells that persisted at low but relatively stable levels despite long-term treatment, thwarting the possibility of HIV being eradicated by ART alone. At the 1998 International AIDS Conference in Geneva, in a plenary talk titled “Cure: Myth or Reality?,” TAG’s executive director, Mark Harrington, discussed the challenge of curing HIV infection.

Also in 1998, TAG joined with amfAR to cosponsor one of the first scientific think tanks to specifically focus on HIV reservoirs (a press release about the event can be found in the document archive of Science writer Jon Cohen at the University of Michigan). Sponsoring face-to-face meetings between key stakeholders—such as scientists, funders, regulators, policy makers, and community activists—has been a cornerstone of TAG’s advocacy, as these events can identify key issues and priorities and generate recommendations for addressing them.

In the late 1990s, TAG also engaged in research advocacy around the issue of ART interruption; part of the impetus for this work came from studies suggesting some individuals might be able to maintain control of HIV replication for an extended period after stopping ART (this rare phenomenon of posttreatment control continues to be a focus in cure research today). In collaboration with the Foundation for AIDS and Immune Research (FAIR), Project Inform, and the Forum for Collaborative HIV Research, TAG cosponsored three workshops on structured treatment interruption research, in 1999, 2000, and 2002. The results from studies prompted by these dialogues are now informing the design of cure-related clinical trials.

In the late 2000s, in light of scientific and technological progress in the field, TAG engaged in discussions with amfAR and Project Inform about reinvigorating research into curing HIV infection. An initial joint scientific workshop was held in Washington, D.C., in November 2008, at which NIAID announced a request for public input to help shape a new grant program for addressing HIV persistence, ultimately leading to the funding of three large research “Collaboratorys” focused on the pursuit of a cure, named after activist and Project Inform founder Martin Delaney: CARE, DARE, and defeatHIV. Subsequent to the meeting amfAR continued to expand its support for cure research, launching the Research Consortium for HIV Eradication (ARCHE).

In the spring of 2011, TAG cosponsored the first workshop on cure-related clinical research with AIDS Policy Project, amfAR, and Project Inform. The aim was to lay the groundwork for an increased number of human trials connected to the field. Among the recommendations was to convene a dialogue between stakeholders and regulatory agencies regarding clinical trial design issues; the Forum for Collaborative HIV Research took on this task as part of its cure project, to which TAG has contributed on an ongoing basis. The Forum sponsored a meeting in Washington, D.C., in June 2014, and TAG’s Mark Harrington and Basic Science, Vaccines, and Cure Project Director Richard Jefferys both participated in the planning and as panelists.

The beginning of this decade also saw the launch of the International AIDS Society (IAS) “Towards an HIV Cure” initiative, and TAG was one of the community-based organizations asked to participate on the steering committee. An IAS scientific workshop on the topic was held immediately ahead of the International AIDS Conference in Vienna in 2010, and was followed up by a symposium in Washington, D.C., in 2012; TAG’s Richard Jefferys authored the meeting reports for both events. TAG also co-organized a community education event on HIV cure research at the 2012 International AIDS Conference in Washington, D.C.

Immediately ahead of the 2012 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, AIDS Treatment Activists Coalition, Project Inform, and TAG held the first pre-CROI Community HIV Cure Research Workshop; these workshops are now held every year on the day before CROI starts, with AVAC joining as cosponsors. A broader educational program on HIV cure research led by Karine Dubé from the CARE collaboratory and Jessica Handibode from AVAC—the CUREiculum Project—was born out of these workshops and launched recently; TAG is among the cosponsors.

The salutary increase in the profile and momentum of HIV cure research in this decade has meant that there are now multiple strands of the effort globally. Curing HIV has become a central priority for NIAID, and it maintains a page providing information on the expanding number of grants awarded in the area. The Martin Delaney Collaboratory grants are due to be renewed and expanded in the near future. Global funding trends are being assessed annually by IAS and AVAC as part of their HIV resource tracking work (an analysis of 2013 investments was published in July 2014). Research collaborations like CHERUB in the United Kingdom have been formed, or are forming, in many countries.

Among the cure research resources offered by TAG are a regularly updated listing of clinical trials (both ongoing and completed), a fact sheet, and a resource page including links to some of the many articles being published on the subject. A section on cure research was added to TAG’s annual Pipeline Report in 2011, and the Michael Palm Basic Science, Vaccines, and Cure Project blog provides updates and commentary on cure-related science. TAG continues to be involved in multiple ongoing cure-related projects and is committed to continuing the work until an effective, broadly accessibly cure for HIV infection is found.

Thanks to the dedicated generosity of all the donors who have supported TAG's cure research advocacy.