30 years after first AIDS cases, hope for a cure

MARILYNN MARCHIONE  |  AP Medical Writer

Today 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.

Nearly 30 million people have died of AIDS since the first five cases were recognized in Los Angeles in 1981.

About 34 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 percent 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.

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.

Other promising approaches to a cure try new ways to attack the dormant virus problem, he said. They hinge on getting people tested and into care as soon as they become infected.

Fauci’s institute has boosted money for cure research, and the International AIDS Society, a professional organization for those who work in the field, has added finding a cure to its strategic plan.

“There are paths forward now” to a day when people with AIDS might be cured, said Dr. Michael Horberg, a member of President Obama’s HIV/AIDS council and vice chairman of the HIV Medicine Association, doctors who treat the disease. “But it’s not tomorrow, and it’s not today.”

—  John Wright

AIDS breakthrough: Gel helps prevent infection

MARILYNN MARCHIONE  |  AP Medical Writer

MILWAUKEE — For the first time, a vaginal gel has proved capable of blocking the AIDS virus: It cut in half a woman’s chances of getting HIV from an infected partner in a study in South Africa. Scientists called it a breakthrough in the long quest for a tool to help women whose partners won’t use condoms.

The results need to be confirmed in another study, and that level of protection is probably not enough to win approval of the microbicide gel in countries like the United States, researchers say. But they are optimistic it can be improved.

“We are giving hope to women,” who account for most new HIV infections, said Michel Sidibe in a statement. He is executive director of the World Health Organization’s UNAIDS program. A gel could “help us break the trajectory of the AIDS epidemic,” he said.

And Dr. Anthony Fauci of the U.S. National Institutes of Health said, “It’s the first time we’ve ever seen any microbicide give a positive result” that scientists agree is true evidence of protection.

The gel, spiked with the AIDS drug tenofovir, cut the risk of HIV infection by 50 percent after one year of use and 39 percent after 2 1/2 years, compared to a gel that contained no medicine.

To be licensed in the U.S., a gel or cream to prevent HIV infection may need to be at least 80 percent effective, Fauci said. That might be achieved by adding more tenofovir or getting women to use it more consistently. In the study, women used the gel only 60 percent of the time; those who used it more often had higher rates of protection.

The gel also cut in half the chances of getting HSV-2, the virus that causes genital herpes. That’s important because other sexually spread diseases raise the risk of catching HIV.

Even partial protection is a huge victory that could be a boon not just in poor countries but for couples anywhere when one partner has HIV and the other does not, said Dr. Salim Abdool Karim, the South African researcher who led the study. In the U.S., nearly a third of new infections each year are among heterosexuals, he noted.

Countries may come to different decisions about whether a gel that offers this amount of protection should be licensed. In South Africa, where one in three girls is infected with HIV by age 20, this gel could prevent 1.3 million infections and 826,000 deaths over the next two decades, he calculated.

He will present results of the study Tuesday at the International AIDS Conference in Vienna. The research was published online Monday by the journal Science.

“We now have a product that potentially can alter the epidemic trends … and save millions of lives,” said Dr. Quarraisha Abdool Karim, the lead researcher’s wife and associate director of the South African program that led the testing.

It’s the second big advance in less than a year on the prevention front. Last fall, scientists reported that an experimental vaccine cut the risk of HIV infection by about 30 percent. Research is under way to try to improve it.

If further study shows the gel to be safe and effective, WHO will work to speed access to it, said its director-general, Dr. Margaret Chan.

The gel is in limited supply; it’s not a commercial product, and was made for this and another ongoing study from drug donated by California-based Gilead Sciences Inc., which sells tenofovir in pill form as Viread. If further study proves the gel effective, a full-scale production system would need to be geared up to make it.

The study tested the gel in 889 heterosexual women in and near Durban, South Africa. Researchers had no information on the women’s partners, but the women were heterosexual and, in general, not in a high-risk group, such as prostitutes.

Half of the women were given the microbicide and the others, a dummy gel. Women were told to use it 12 hours before sex and as soon as possible within 12 hours afterward.

At the study’s end, there were 38 HIV infections among the microbicide group versus 60 in the others.

The gel seemed safe — only mild diarrhea was slightly more common among those using it. Surveys showed that the vast majority of women found it easy to use and said their partners didn’t mind it. And 99 percent of the women said they would use the gel if they knew for sure that it prevented HIV.

This shows that new studies testing the gel’s effectiveness without a placebo group should immediately be launched, said Salim Abdool Karim. The only other study testing the gel now compares it to placebo and will take a couple more years to complete.

The study was sponsored by the Centre for the AIDS Programme of Research in South Africa, or CAPRISA; Family Health International; CONRAD, an AIDS research effort based at Eastern Virginia Medical School; and the U.S. Agency for International Development, or USAID.

Gilead has licensed the rights to produce the gel, royalty-free, to CONRAD and the International Partnership on Microbicides for the 95 poorest countries in the world, said Dr. Howard Jaffe, president of the Gilead Foundation, the company’s philanthropic arm.

The biggest cost of the gel is the plastic applicator — about 32 cents, which hopefully would be lower when mass-produced, researchers said.

Mitchell Warren, head of the AIDS Vaccine Advocacy Coalition, a nonprofit group that works on HIV prevention tools, said the study shows a preventive gel is possible.

“We can now say with great certainty that the concept has been proved. And that in itself is a day for celebration,” he said.

—  John Wright