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Research Alert: Study Casts Doubt on "Shock and Kill" Cure Strategy

TAG Sponsors "Cure Meeting"

Winter 2008/2009

Scientists, funders, and activists meet in Washington, D.C., to speed research to eradicate or permanently deactivate HIV in the body.

In November 2008, Treatment Action Group, the Foundation for AIDS Research, and the FAIR Foundation sponsored a long-overdue meeting of leading scientists in Washington, D.C., to discuss the possible avenues -- and impediments -- to finding a way to eliminate or cause the long-term remission of HIV in the body. Among the sponsors, the Workshop on Eliminating Viral Persistence and Eradicating HIV Infection was informally known as the "Cure Meeting."

Finding a cure for HIV has taken a backseat to efforts to develop treatments and ways to prevent new infections. The quest for an AIDS treatment -- so painfully slow in coming -- was successful beyond imagination when it was finally achieved in 1996. In the dozen years since effective HIV therapy became widely available in the United States, over 26 drugs have been approved, with potency and tolerability increasing along the way.

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The search for a vaccine to prevent HIV infection has not gone as smoothly. In the nearly quarter century since Ronald Reagan's secretary of Health and Human Services, Margaret Heckler, predicted an AIDS vaccine within a few years, the search appears to be perpetually frustrated by a lack of basic scientific knowledge about the human immune system and what happens when HIV intrudes.

TAG executive director Mark Harrington addressed the XVII International AIDS Conference 2008 in Centro Banamex, Mexico City, August 6, 2008. Harrington delivered 'Looking to the Future: The Epidemic in 2031 and New Directions in AIDS Research.'
TAG executive director Mark Harrington addressed the XVII International AIDS Conference 2008 in Centro Banamex, Mexico City, August 6, 2008. Harrington delivered "Looking to the Future: The Epidemic in 2031 and New Directions in AIDS Research."
© International AIDS Society / Mondaphoto
Hopes of permanently curing HIV infection never soared very high after it was discovered that the virus actually inserts its DNA into the DNA of its target immune cells. New viruses are made as a by-product of the cell's transcribing DNA to perform its normal functions. Some of these infected immune cells can quietly hide in lymph nodes for years, harboring a hidden reservoir of virus. When the new treatments were pioneered in 1996, it was hoped that over time these cells would die off and, if the drugs prevented any new cells from becoming infected, the infection would eventually burn itself out. Mathematical estimations of this scenario soon showed that -- even if perfect suppression could be achieved -- it may take 20 years or more to eradicate HIV from the body with drugs alone. After that disappointment, hopes for a cure dimmed as science turned to the more realistic goals of improving treatments and discovering a vaccine.

In 2007, the first of a new class of drugs called integrase inhibitors was approved by the FDA. These new drugs work by preventing the viral DNA from inserting itself into the immune cell's DNA. Some think that they may pose a nearly impenetrable barrier to new infections. The potency of integrase inhibitors has stimulated interest in bringing virus levels far lower than had been previously thought possible and has revived talk of eradicating HIV. But the long life of the infected reservoir cells is still a problem.

One approach to flushing the reservoir has been to stimulate the resting cells into action, thus luring out the silent HIV so it becomes susceptible to antiviral drugs. Early attempts used agents that stimulated the immune system too indiscriminately and were scuttled by toxicity. Some scientists are now proposing ideas for stimulating hidden HIV-infected cells with greater precision. Others think it may be possible to identify the cells and specifically target them for destruction. Still others think it may be possible to permanently switch off mechanisms in the cells that HIV depends on for replication. Compared to the search for a vaccine, finding a cure for HIV has come to seem almost plausible and cautious optimism has returned to the field.

Yet there are many hurdles to overcome -- some scientific, but many bureaucratic, which is why TAG organized the Cure Meeting in Washington.

Many scientists say they have good ideas that need to be tested in people but cannot obtain funding because the current grant mechanisms of the National Institutes for Health (NIH) are not oriented to support so-called translational research that moves therapies from the laboratory to the clinic. Other barriers involve FDA guidelines for how research can be performed on people; some of these requirements limit what university-based scientists can accomplish on limited budgets.

Pharmaceutical industry cooperation will also be required to test innovative concepts for eliminating HIV. New compounds being developed by small biotechnology companies for other diseases may have potential for this research. Yet HIV scientists are often unable to access these experimental agents because companies don't want to jeopardize their goal of achieving FDA approval for their target market. Scientists need a method for obtaining these drugs while indemnifying the companies in case unanticipated toxicities appear in people with HIV.

The Cure Meeting invited key leaders from the NIH; other, nongovernmental funders of AIDS research; the FDA; top scientists working in the field of HIV persistence and eradication; doctors involved with cutting-edge HIV studies; and HIV treatment activists. Discussion was divided between roadblocks and opportunities, both in the science and in the funding and practical spheres.

TAG plans to follow up on the directions outlined at the meeting with an advocacy campaign aimed at revitalizing research to permanently defeat HIV.




This article was provided by Treatment Action Group. It is a part of the publication TAG Update.
 

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