Sunday marks 30 years since the first AIDS cases were reported in the United States, and this anniversary brings fresh hope for something many had come to think was impossible: finding a cure.
The example is Timothy Ray Brown of San Francisco, the first person in the world apparently cured of AIDS. His treatment isn't practical for wide use, but there are encouraging signs that other approaches might someday lead to a cure, or at least allow some people to control HIV without needing medication every day.
"I want to pull out all the stops to go for it," though cure is still a very difficult goal, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
For now, the focus remains on preventing new infections. With recent progress on novel ways to do that and a partially effective vaccine, "we're starting to get the feel that we can really get our arms around this pandemic," Fauci said.
More than 25 million people have died of AIDS since the first five cases were recognized in Los Angeles in 1981.
More than 33 million people have HIV now, including more than 1 million in the United States.
About 2 million people die of the disease each year, mostly in poor countries that lack treatment. In the U.S. though, newly diagnosed patients have a life expectancy only a few months shorter than people without HIV. Modern drugs are much easier to take, and many patients get by on a single pill a day.
But it wasn't that way in 1995, when Brown, an American working as a translator in Berlin, learned he had HIV. He went on and off medicines because of side-effects but was holding his own until 2006, when he was diagnosed with leukemia, a problem unrelated to HIV. Chemotherapy left him so sick he had to be put into a coma to allow his body to recover.
"They didn't know if I'd survive that," Brown said.
Dr. Gero Huetter, a blood cancer expert at the University of Berlin, knew that a transplant of blood stem cells (doctors used to use bone marrow) was the best hope for curing Brown's cancer. But he aimed even higher.
"I remembered something I had read in a 1996 report from a study of people who were exposed to HIV but didn't get infected," Huetter said.
These people had gene mutations that provide natural resistance to the virus. About 1 per cent of whites have them, and Huetter proposed searching for a person who also was a tissue match for Brown.
But transplants are grueling. Huetter would have to destroy Brown's diseased immune system with chemo and radiation, then transplant the donor's cells and hope they would take hold and grow. Many cancer patients die from such attempts and Brown wasn't willing to risk it.
His mother, Sharon Brown of Seattle, agreed.
"Before I knew he had HIV I used to have nightmares about it," and gambling on a transplant to try to cure it didn't seem smart when the cancer seemed to be in remission, she said.
Several months later, the return of leukemia changed their minds.
Brown discussed the transplant with his boss "and she said, 'wow, this is amazing. Because you have leukemia, you could be cured of HIV."'
A registry turned up more than 200 possible donors and Huetter started testing them for the HIV resistance gene. He hit pay dirt at No. 61 — a German man living in the United States, around 25 years old.
Brown had the transplant in February 2007. A year later, his leukemia returned but HIV did not. He had a second transplant in March 2008 from the same donor.
No evidence of HIV
Now 45, Brown needs no medicines, and his only health problems are from the mugging he suffered two years ago as he returned home one night in Berlin. Brown was knocked unconscious, required brain surgery and therapy to walk and talk again, and doesn't have full use of one arm. He moved back to the United States in December.
"He's now four years off his antiretroviral therapy and we have no evidence of HIV in any tissue or blood that we have tested," even places where the virus can lie dormant for many years, Huetter said.
Brown's success inspired scientists to try a similar but less harsh tactic: modifying some of a patient's infection-fighting blood cells to contain the mutation and resist HIV. In theory, this would strengthen the immune system enough that people would no longer need to take HIV drugs to keep the virus suppressed.
Scientists recently tried this gene therapy in a couple dozen patients, including Matthew Sharp of suburban San Francisco. More than six months later, the number of his infection-fighting blood cells is "still significantly higher than baseline," he said.
It will take more time to know if gene therapy works and is safe. Experiments on dozens of patients are under way, including some where patients go off their HIV medicines and doctors watch to see if the modified cells control the virus.
The results so far on the cell counts "are all wonderful findings but they could all amount to nothing" unless HIV stays suppressed, said Dr. Jacob Lalezari, director of Quest Clinical Research in San Francisco who is leading one of the studies.
The approach also is not practical for poor countries.
"I wouldn't want people to think that gene therapy is going to be something you can do on 33 million people," said Fauci.