Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte.
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One June afternoon in 1992, a dancer named Matthew Sharp died eight times. A siren shrilled as he repeatedly dropped to the street and let strangers draw a chalk outline around his body. Then he stood up, took the chalk, and each time wrote the name of his partner, Johnny Franklin, inside the empty space—just like a cop at a crime scene.

Franklin had succumbed to AIDS in Oklahoma City two years earlier, and now Sharp was marching with the AIDS awareness group Act Up along Market Street in San Francisco’s annual gay pride parade. “Die-ins were a common form of AIDS activism in the 1980s and 1990s,” Sharp recalls. “They were conducted in complete silence every seven minutes while we were marching, because that was how often someone died of AIDS back then.”

After Franklin’s death, Sharp nearly became another victim when he came down with extrapulmonary tuberculosis. “I felt I was knocking on death’s door,” he says. “So I quit my ballet company, took the life insurance money Johnny left me, and moved to San Francisco, which was ground zero for HIV,” the AIDS virus. “For the next 20 years I stayed alive by participating in clinical trials of new drugs before they were released. I was aggressive about preventing opportunistic infections. When I began to die of wasting syndrome, I joined a trial for human growth hormone. I got an experimental thymus transplant. Combination therapy in 2008 finally brought my viral load down to undetectable.”


Still, there was the problem of Sharp’s T cells—the white blood cells, or lymphocytes, that unleash a powerful immune response against pathogens like HIV. For AIDS, the most critical of the T cells is CD4, which would normally coordinate the body’s attack against the disease. But by a quirk of biology, CD4 cells end up sequestering the virus, which ultimately decimates them. With Sharp’s CD4 cells hovering at around 250 per cubic millimeter of blood—a normal count is 500 to 1,500—he was prone to a host of opportunistic infections and qualified for a diagnosis of full-blown AIDS. “I was always in the danger zone, and every year I would come down with pneumonia,” Sharp says.

Then came an invitation to participate in a novel form of gene therapy, one that could mark a first step toward a true cure for AIDS. The trial was run by Jay Lalezari, director of Quest Clinical Research in San Francisco. Sharp agreed to join. His blood was drawn and his CD4 cells were filtered out, frozen, and transported to a laboratory where they were genetically altered to resist invasion by HIV. This was done by deleting a receptor on the surface of the CD4 cell that HIV uses to get inside. The reengineered CD4 cells were allowed to multiply in the lab and then returned to Lalezari.

In September 2010 Sharp received a single infusion of 20 billion of his genetically engineered immune cells. Within weeks his CD4 count doubled. “They test me every month and my CD4 count hasn’t fallen below 400. I haven’t had the usual bout of pneumonia since this treatment. I’d love to get a second infusion,” Sharp says. “I’m 55 years old and feeling better than ever, and now there’s a possibility I’ll actually see a full cure of HIV in my lifetime.”

“We can’t be complacent. It’s an active, untreated epidemic in other parts of the world. It could change and come back to haunt us in a new form.”

Curing AIDS? Wiping out a pandemic that currently affects 33 million adults and 2.5 million children worldwide and infects 7,000 new people every day? In the 30 years since scientists identified HIV as the cause of AIDS, the virus has proved unbeatable—hiding in the very immune cells that would kill it; reflexively and rapidly mutating; mysteriously persisting in the gut, kidneys, liver, and brain; subverting every vaccine (the best one so far has given only 30 percent protection); and roaring back to life almost the moment drugs are stopped. It has been years since anyone dared whisper the word cure at all.

But they are daring again with growing confidence, buoyed by new insights and technologies to fight a foe that Jay Levy, codiscoverer of HIV, compares to a “biological Trojan horse” and Jay Lalezari calls “a cellular bioterrorist that kills your first responders first.” Tapping into medical advances from gene therapy to stem cells, researchers are launching powerful counterstrikes against the virus. The National Institutes of Health (NIH) will invest $70 million over the next five years to support three multi-institution research efforts aimed at finding a cure. And the independent International AIDS Society, known for its conferences, has assembled a working group of world experts to spearhead a global strategy for the cure.

The latest turn seems as remarkable as the one patients celebrated in 1996, when David Ho of Rockefeller University in New York presented his research on a combination drug therapy, a treatment cocktail that rendered the virus undetectable in blood. That work turned AIDS from a certain killer into a chronic disease almost overnight. “I remember witnessing a miracle,” recalls Steven Deeks, an expert in the pathogenesis of HIV at the University of California, San Francisco (UCSF). “Literally within weeks, people went from a death sentence to a promise of years of health. People in hospices were sent home. And now there is a possibility we’ll have another dramatic shift.” He cautions, however, that it took “15 years to get from that first antiviral to truly effective, well-tolerated combination therapy. I think in terms of a total cure, we’re just now starting another 15-year journey.”