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for HIV-infected people for years, now has patients who have kept the virus completely in check with drugs for up to 17 years. “They’re going to outlive me,” says Richman, who is 67 years old. “They’re not going to die of AIDS. That’s wonderful, but do we have to have tens of millions of people on lifetime treatment?”

Such treatment has rising costs, both monetary and medical. In wealthy countries, annual drug expenses run into the thousands of dollars per HIV-infected person. Much cheaper generic versions of the drugs have been given to four million patients in poor countries, but the rich governments footing most of that bill are now cash-strapped and worried about sustaining the charity. And an estimated five and a half million more people urgently need treatment but have no access.

What’s more, living with HIV for decades can be medically problematic. Even low levels of the virus can leave patients more susceptible to diseases of aging: heart attacks, malignancies, disorders of the central nervous system. Some of these ailments are side effects of the drugs themselves. People on treatment can have damaging surges of virus, too, when they occasionally stop their drugs or develop resistance to the compounds. “There are five million new infections a year, and three million deaths,” says ­Richman. “So we’re just going to have more and more people living with HIV.”

Cannon’s gene therapy experiment is one of a dozen similar projects in the works that hold the promise of ending patients’ dependence on antiretroviral drugs. It’s an ambitious dream. But it’s no longer as quixotic as it once seemed, and she is approaching her experiment with realistic expectations and the conviction that other researchers’ progress will work in concert with her own. “I think in steps,” says Cannon. “Will the first person on our treatment be the home run? No. But we may see some benefit. And if you have an imperfect success, it’s still a success.” Especially when the goal is so grand that it could profoundly alter millions of individual lives–and the course of the AIDS epidemic itself.

Taboo

Talk of a cure began shortly after the epidemic surfaced in 1981, but for 15 years it was just talk. Even the best HIV treatments did little to hamper the virus. Then, in 1996, researchers reported a remarkable breakthrough using new combinations of antiretrovirals: they could suppress the amount of virus in the blood below the levels that standard tests could detect, allowing immune systems to rebound and people near death to resume normal, healthy lives. Small amounts of the virus could still be detected in these patients by running more sensitive blood tests and analyzing hideaways like lymph nodes or the gut, but the dramatic success of the treatment led prominent AIDS researchers to believe for the first time that the idea of curing HIV was truly realistic.

David Ho, head of the Aaron Diamond AIDS Research Center in New York City, became a media sensation after he spoke at the international AIDS conference held in Vancouver, British Columbia, in July 1996. Ho had done mathematical calculations showing that if drugs could suppress the virus to this degree, it would take, at most, around three years to eradicate HIV from a patient. His clinical team had an ideal population in which to test the theory: eight patients who had started the powerful drug cocktails shortly after becoming infected, which presumably prevented the virus from ever multiplying to astronomical levels. If all went well for a few more years, these people would stop taking their treatments and, the investigators hoped, never see the virus return.

Flushed out: HIV that hides in resting immune cells must be awakened before it can be eradicated. In the general scheme for accomplishing this, the HIV is activated by opening tightly coiled viral DNA, leading to the production of viral particles. Drugs prevent the resulting new viruses from infecting healthy cells, and the HIV is eventually flushed out of the body. In a variation that Paula Cannon is testing in mice, T cells are modified to resist HIV, denying the virus new targets if resting infected cells become active.
Download a PDF of the infographic.

As much as the headlines celebrated Ho–Time magazine named him Man of the Year in 1996–many colleagues were deeply skeptical. “In every field–pancreatic cancer or brain cancer or Alzheimer’s–it’s okay to say ‘I’m working on a cure,’  ” Ho says. “For HIV/AIDS, it was a taboo.”

In May 1997, when Ho and his collaborators published their calculations in Nature, they emphasized that surprises might be lurking around the corner. “Although significant progress has been made in the past year in the treatment of HIV-1 infection, it would be wrong to believe that we are close to a cure for AIDS,” they wrote.

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Credits: Daniel Hennessy, Tami Tolpa

Tagged: Biomedicine

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