The Man Who Could Beat AIDS

Dr. David Ho was sitting in the audience during an AIDS meeting in 2007 when the presenter flashed a cartoon onscreen to make a point. Along with his colleagues, Ho chuckled at the image of a blindfolded baseball player swinging mightily at an incoming pitch. But as amused as the scientists were, they were sobered too; they knew that the player in the cartoon was them. A swing and a miss, the image was saying, one of many in the long battle against AIDS.

Ho certainly got the message. For nearly a quarter of a century, he and other AIDS scientists had been whiffing repeatedly, failing to make contact as HIV stymied them again and again. Powerful drugs to foil HIV could do only so much. To corral the epidemic and truly prevent HIV, only a vaccine would do. The problem was that no vaccine strategy had ever succeeded in blocking the virus from infecting new hosts, and that wasn't likely to change in the near future. "It struck a special chord with me," says Ho of the baseball image. "I think it accurately pictured our chance of success. We all felt that frustration."

Since that meeting, much has changed, but the fundamental problem of developing an effective AIDS vaccine remains. On the positive side, in 2009, scientists announced that they had developed the first vaccine to show any effect against HIV infection — although that effect is, by all measures, modest. The vaccine's ability to reduce the risk of new HIV infection 31% is nowhere near the 70% to 90% that public-health experts normally view as a minimum threshold for an infectious-disease vaccine. Even further behind in development, but still promising, are two new antibodies identified by a group of researchers working at a number of labs that, at least in a dish, seem to neutralize the virus and thwart attempts to infect healthy cells.

The excitement over those advances, however, has been tempered by the still raw memories of a humbling retreat in 2007, after a highly anticipated shot against the virus was deemed a failure. While nobody expected spectacular results, neither did anyone expect such a stunning defeat, and the scientific community is still struggling to recover from it. "We are still a long ways away from having an effective HIV vaccine that physicians can reach into the cabinet and pull out in a vial and inject into a person," says Dr. Bruce Walker, an HIV expert at Harvard Medical School.

That may be true, but Ho, who has been working to develop an HIV vaccine of his own, now believes that a traditional shot, one that relies on snippets of a virus to both awaken and prod the immune system to churn out antibodies, may not be the best way to fight HIV. Rather than expecting the body to do all the work of first recognizing then mounting an attack against the virus, why not just present the body with a ready-made arsenal of antibodies that can home in on HIV? It's the immunological equivalent of a frozen dinner; the already cooked antibodies eliminate all the hard work of prepping and priming the immune system to do battle.

It's a bold strategy and one that has never been tried before in the AIDS field, but Ho is willing to stake his reputation and that of his nearly 20-year-old facility, the Aaron Diamond AIDS Research Center (ADARC) in New York City, on his hunch. So is the Bill & Melinda Gates Foundation, which has steered nearly $7 million his way to pursue the theory. Ho has redirected more than half of his lab to the project, and the results so far have reignited his passion for discovery; he's now back at the lab bench overseeing experiments.

Ho can't help breaking into a grin whenever he discusses the new project, and smiles haven't come easily to him of late. In the 1990s, he and ADARC established themselves as leaders in the AIDS field by pioneering the early use of the antiretroviral (ARV) cocktails that have reduced the death rate from AIDS (for which Ho was named TIME's Person of the Year in 1996). But in recent years, the center has suffered a series of setbacks, including a scientific paper that required a partial retraction, and the departure of key scientists. These challenges have some in the field wondering whether ADARC — and its golden-boy director — are on the verge of the next big breakthrough in AIDS or are wandering down yet another detour in the long and maddening fight against the disease.

First Responder
Whatever successes Ho does or doesn't have ahead of him, he long ago earned his credentials in the AIDS field. As a physician at the University of California, Los Angeles, in the early 1980s, he began keeping a diary of patients who were rushed to the emergency room with a mysterious amalgam of symptoms such as pneumonia, cancer and, most important, a devastating drop in immune function. After a few months, he noticed a pattern: most of the patients were gay men. Intrigued, he became nearly obsessive about chronicling the growing wave of cases. Within two years, Ho and the rest of the world would know that they were seeing the first cases of AIDS.

Ho's preoccupation with HIV only grew as the virus continued to baffle scientists. Expecting the unexpected was the best way to confront HIV, he soon learned, and he quickly amassed an impressive array of scientific firsts in the field. As director of ADARC, which was founded in 1991 and was one of the first research centers dedicated solely to the study of AIDS, he led a team that pioneered the "hit 'em early and hit 'em hard" approach to drug therapy, now the core of the ARV-cocktail treatment that is keeping millions of HIV-positive patients alive. His lab showed how HIV therapies would be most effective in the days and weeks immediately after HIV infected a new host. That understanding came from their breakthrough finding that rather than sitting latent for years after infection, as many experts believed at the time, HIV was actively challenging the immune system from Day One. Soon after that revelation, ADARC scientists were the first to add to existing data on how HIV worked by identifying a second, key receptor that the virus uses to invade cells.

Vaccines in Vain
But while AIDS scientists began making inroads in developing drug therapies, designing a vaccine was proving nearly impossible. Despite all that they have learned about HIV, experts are still missing one essential ingredient: to this day, they do not know exactly what cells or immune responses could protect the body from HIV infection. Could an antibody that binds to and neutralizes the virus do the trick? Are T cells, specially formulated to recognize portions of HIV's surface proteins, the solution? Or, as many experts now suspect, is some elusive combination of those factors the key to outwitting HIV?

Without an answer, developing vaccines is a very halting process. "The virus is a moving target," says Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health (NIH). "It is constantly changing its genetic makeup through mutations. It's also a moving target because the proteins of the virus surface are actually moving themselves — they are conformationally flexible. The net result is that the immune system never gets a really good look at them."

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