San Francisco Chronicle - Friday, March 6, 2009
David Perlman, Chronicle Science Editor

The goal - admittedly a longshot - is to find a path that would free every infected patient in the world from both the AIDS-causing virus and from lifelong dependence on the drugs that can hold the virus at bay, but are far too costly for most of the underdeveloped nations of the world.

In a sense, the call for a collaborative effort to end to the viral infection that - untreated - ends in death from outright AIDS is a voice from beyond the grave of AIDS advocate Martin Delaney, founder and longtime director of San Francisco's Project Inform, who died six weeks ago of liver cancer.

Before he died, Delaney, whose organization remains a major source of information, advocacy and activism on behalf of AIDS patients around the globe, had joined the scientists in meetings to draw up plans for what they are terming a "collaboratory," the coordination of years of research in a new venture with an unpredictable payoff.

As successful as they are in combatting the AIDS virus, the drug combinations now available cannot eliminate every virus particle from the bodies of those who are infected. Those dormant particles - latent is the medical term - pose an ongoing threat of renewed infection without lifelong use of those antiviral drugs.

The ultimate goal

The scientists' ultimate goal is to find ways to purge those latent virus particles from every AIDS-infected person, and thereby forestall permanent dependence on those overwhelmingly expensive drugs.

In their challenge to AIDS researchers worldwide, the U.S. scientists have published a review paper in the journal Science with Delaney listed as co-author. The paper, which is also dedicated to Delaney because of his participation as a "friend and colleague," appears today.

Its authors include Douglas D. Richman of UC San Diego, Warner C. Greene of UCSF's Gladstone Institute of Virology and Immunology, Daria Hazuda of pharmaceutical giant Merck, Roger J. Pomerantz of Johnson & Johnson and David M. Margolis of the University of North Carolina.

Their paper is titled "The Challenge of Finding a Cure for HIV Infection."

By killing virtually all the latent viruses in the cells of infected people - even in those who live in good health while taking the antiviral drugs, the researchers hope the immune systems of those who are infected would be empowered to cope with any few virus particles that remain without ever requiring more antiviral drug therapy.

"The big question," said Greene in an interview, "is how do we turn against a silent virus when we can't kill it until it expresses itself? It calls for a fundamentally different approach to cure the HIV infection, and it's an extremely tough goal that may not even succeed."

The emergence of an idea

The idea for the new approach had its origin in 1996, at the sixth International AIDS Conference in Vancouver, British Columbia, when combinations of then new drugs called protease inhibitors were shown to be highly effective in suppressing virus infections and returning even sick AIDS patients to apparently healthy lives - as long as they continued the drugs.

Since then, expensive "cocktails" of three or more drugs have become standard in what is known as HAART, for Highly Active Anti-Retroviral Therapy, and only two years ago three of those drugs were combined into a single pill taken once a day. But the cost remains high, and few, if any, nations in the developing world can afford them for their millions of people living with HIV infections or with AIDS itself.

More than 33 million people around the world are now living with HIV infections or AIDS, according to the United Nations, but only 4 million are receiving the HAART drugs - of whom 1 million are in the United States.

The collaborative effort toward "curing" HIV infections and a drug-free future for everyone infected was last discussed in detail at a Washington meeting of AIDS researchers with Delaney and other activist leaders less than a year ago, according to Anthony J. Fauci, director of the National Institute of Allergy and Infectious Diseases, the leading government AIDS-fighting agency.

Fauci spoke at that meeting, and told The Chronicle on Thursday that he endorsed the effort strongly and would support it. The AIDS budget for his institute and others within the National Institutes of Health, he said, is now about $2.9 billion, and it is already funding some of the approaches the new collaborators are seeking.

"Finding a cure for HIV infection may be a pie-in-the-sky idea," Fauci said, "but it would mean you could stop drug therapy and the virus wouldn't bounce back. Marty (Delaney) and I had been talking about this possibility for a long time, and it's a great idea. It may never succeed but it's surely worth trying."

E-mail David Perlman at dperlman@sfchronicle.com.
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