Treatment News : Report Outlines HIV Cure Research, Important Gaps - by Tim Horn

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April 25, 2012

Report Outlines HIV Cure Research, Important Gaps

by Tim Horn

Three HIV/AIDS activist groups convened a meeting in March with researchers and representatives of the U.S. Food and Drug Administration (FDA) to describe the current state of cure research and identify barriers to moving such research forward swiftly and smoothly. The proceedings of this meeting, which took place immediately before the 19th Conference on Retroviruses and Opportunistic Infections (CROI) that began on March 5 in Seattle, are now available in a report online.

“A cure for HIV will be essential to ending the AIDS pandemic, but science that is focused directly on a cure is still in early stages and will likely require the support of multiple stakeholders to proceed at the fastest pace,” reads the executive summary of the report, authored by David Evans, Kevin Fisher, Jeff Taylor and Siegfried Schwarze.

In the past four years, the report notes, there have been signs of increasing scientific momentum and funding directed toward curing HIV infection.

The remarkable case of “Berlin Patient” Timothy Brown—a man who all signs suggest has been cured of HIV—has catalyzed and expanded what was once a small and somewhat fragmented effort to understand how HIV persists despite effective antiretroviral (ARV) therapy and to explore mechanisms to eliminate the hidden pool of virus in people on ARV treatment (a sterilizing cure) or to enable the immune system to control HIV without the need for ARVs (a functional cure).

This momentum, the activists write, has been greatly enhanced by the NIH-funded Martin Delaney Collaboratory projects, partnerships between academia and industry focused on the possibility of discovering and developing a safe, effective, feasible and scalable HIV cure.

Among recent signs of progress, researchers have contributed new insights into where and why HIV persists despite potent ARV therapy. In addition, the first controlled clinical trials of drugs to activate cells harboring archived HIV, such as histone deacetylase (HDAC) inhibitors, are yielding promising signals, and other types of treatments designed to teach the immune system to either clear or control the virus on its own have been initiated.

But central questions remain, the report stresses.

For example, it is still not clear what types of cells and anatomical compartments harbor HIV, nor is it understood which methods work best for measuring the latent virus in these reservoirs. Knowledge regarding how HIV is able to replenish these reservoirs, even when ARVs with “maximally suppressive” effects on viral load are being used consistently and correctly, is also needed. Actually, it’s not entirely clear if modern ARV therapy is, in fact, fully suppressing HIV replication. And does the immune system play a role in HIV persistence? In addition, what are the forms of immunologic HIV control that can potentially be enhanced without major safety issues?

Finally, the report asks, what are “reasonable” risks for the people living with HIV who will be participating in early—and potentially dangerous—studies, and how can these individuals be best protected?

To address these questions, members of the AIDS Treatment Activists Coalition (ATAC), the Treatment Action Group (TAG) and Project Inform sat down with several industry and academic researchers on March 4 in Seattle, who described their current projects, outlined the obstacles and facilitators to cure research and offered suggestions for the kinds of activities that community advocates might undertake to overcome current obstacles.

Highlights include: an overview of AIDS Clinical Trials Group (ACTG) clinical trial development by Dan Kuritzkes, MD; laboratory testing for new compounds, including work being conducted by Romas Geleziunas, PhD, at Gilead Sciences; the prospects of gene therapy, notably ongoing zinc finger nuclease work at Sangamo Biosciences, discussed by Dale Ando, MD; stem cell research after the Berlin Patient, highlighted by John Zaia, MD, who underscored the importance of not overselling this approach; and work focusing on the enhancement of immune responses, reviewed by Pablo Tebas, MD.

The post-meeting report, issued in April, provides a brief synopsis of each presentation, followed by an outline of areas identified by the workshop speakers and participants for further exploration, development and incorporation into a cure advocacy agenda.

“The prevailing view of all the speakers was that we must not raise premature and unrealistic hopes of a cure for HIV either in people who volunteer their bodies for cure research, or in the wider community of people with HIV and their allies,” the authors write. “Critical early steps have been identified, but we need many more successes in analytics, basic science and translational research—in both animals and people—before the cure will be within our grasp.”

Search: cure, research, science, advocacy, activism, treatment action group, tag, aids treatment activists coalition, atac, project inform, gene therapy, immune-based therapy, stem cells, therapeutic vaccines

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