translation agency

New York Times
'Cured of AIDS'? Not Yet

<p>Donald G. McNeil Jr.</p>


April 29, 2013

What to make of all the recent "cured of AIDS" headlines? An American in Berlin, a baby in Mississippi and 14 patients in France are all alive without treatment.

Is a cure at hand?

No. But in unusual cases, some people seem able, with temporary help from antiretroviral drugs, to kill the virus before it can sink into reservoirs deep in their bodies - or to at least force it to stand at the doorways of their cells, unable to get in.

"I'm excited about this," said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases. "Not that we've got a cure, but things are falling into place that tell us what goes into the process of infection. So we're learning whom we can potentially take off treatment."

Does that mean doctors should now encourage H.I.V. patients to stop treatment?

Absolutely not, experts agree. There is no way to tell which patient might get lucky, and a vast majority will not. And "drug holidays," which were in vogue a few years ago among patients tired of side effects, worked out badly when they were tested in clinical trials.

But several experts say the reported cures - if confirmed by others - do suggest that some AIDS policies should change in at least two ways.

First, instead of waiting for the infected to wander into testing clinics, health authorities ought to be aggressively seeking them out.

Second, those who test positive ought not to dither about taking medication.

Early treatment now has three clear benefits for patients: They may live longer, may be 96 percent less likely to infect anyone else and may turn out to be among the lucky few who can stop later.

"We should seek out, test and get people into treatment as soon as we possibly can," Dr. Fauci said. "That way, you can get people into the position the Visconti cohort is in."

("Visconti cohort," for Viro-Immunologic Sustained Control After Treatment Interruption, is a shorthand way of referring to the patients studied by the Pasteur Institute, in France.)

The virus's march into the body now looks less unstoppable. H.I.V. doesn't just hide behind cell walls, as flu viruses do. It splices a copy of itself right into the genes of certain white blood cells, adding permanent new rungs to each cell's DNA ladder. Later, it does the same to cells in the bone marrow, lymph nodes, nerves and organs.

Scientists now can biopsy various cells and force them to spit out some viral RNA, proving that they are infected.

"We're getting better at defining the reservoirs," said Jerome Zack, an immunologist at the David Geffen School of Medicine at the University of California, Los Angeles. "But there are still arguments among scientists about whether there are places deep in the tissues that treatment doesn't reach, and whether or not virus is still replicating there."

The Berlin patient, Timothy Ray Brown, is in his own category. A Seattle native formerly living in Germany, he had been on drugs for 11 years when he developed leukemia, a blood cancer. That led to the procedure that earned him a place in medical history: In 2006, his German doctors wiped out his bone marrow and gave him marrow from a matching donor who also had the rare "delta 32 mutation" that makes CD4 cells, the virus's favorite target, impervious to H.I.V.

Last week, doctors at the University of Minnesota performed the same procedure on an unnamed 12-year-old boy with both H.I.V. and leukemia, using umbilical cord blood from a newborn with the same mutation. It will be months before they know whether it worked.

Mr. Brown, 47, may still have a hidden viral reservoir, but apparently it cannot infect his blood cells.

In an interview from Las Vegas, where he now lives, he said he was "very excited" by the news of the baby in Mississippi and the French patients.

"I felt kind of lonely being the only person in the world cured," he said.

But typical patients can't follow his lead. Wiping out bone marrow normally carries a 40 percent risk of death, and Mr. Brown had to have it done twice. His doctor later told him that he thought he had a 95 percent chance of dying the second time.

By contrast, the Mississippi baby was put on full antiretroviral treatment, rather than just a typical lower-dose prophylactic regimen, just 30 hours after it was born about three years ago, and stayed on it for 18 months before the mother, for her own reasons, stopped it for five months. At the next doctor's appointment, the baby - astonishingly - appeared cured.

In follow-up research, no matter which cells Dr. Deborah Persaud of Johns Hopkins Children's Center tested, she could not find any viral RNA. All she found, she said, were "graveyard sequences" of nonworking DNA, presumably remnants of the initial infection. (The child is still apparently healthy.) Some scientists remained skeptical, saying that the baby might have a reservoir in cells so deep in the body that they could be tested only in an autopsy.

In this country, it is unusual for an infected pregnant woman to not see a doctor even once before delivery. But in Africa, the problem is common. If the Mississippi baby's experience is repeated - probably by chance, because it would be unethical for a doctor to advise a mother to take her infected child off antiretrovirals - it may become routine for babies in such circumstances to get an aggressive drug regimen, not just the prophylactic one.

By contrast, the French patients went on treatment within weeks or months after infection and stayed on for a year or more. Later, some - but only about 15 percent of them - were able to stop their drugs.

Catching patients early is difficult. Not all get the first temporary signs of H.I.V. infection - fever, sore throat, swollen glands and a rash. Complicating matters, those symptoms resemble mononucleosis, Epstein-Barr virus and the flu, said Dr. Eric S. Rosenberg, an H.I.V. researcher at Massachusetts General Hospital.

In the 1990s, Dr. Rosenberg started what another AIDS expert referred to as the "Rosenberg cohort" but which Dr. Rosenberg called the "Boston cohort."

About 300 patients are in it, he said. Like the French group, it comprises patients who were put on drugs early. Dr. Rosenberg noticed that some had different immune responses and wondered if those could be taken off treatment briefly.

The model for trying that, he said was "the original Berlin patient."

That patient, profiled in magazines in 1998, was an anonymous German who, of his own volition, stopped taking his drugs after six months, but did not get sick.

"The hypothesis at the time was that he was started so early that he could control the virus," Dr. Rosenberg said.

Under supervision, some of Dr. Rosenberg's patients tried it. "In some people, it seemed to work, and in some people it didn't work at all," he said.

That is essentially what happened in the Visconti cohort. Asked why the latter group leapt to fame but his did not, Dr. Rosenberg speculated that it might have been because his was created to study patients' immunology over their lifetimes, not as a specific trial of treatment interruption with a formal end date.

Also, he said, "for none of our patients would we have used the word 'cured.' "

While there is no clear indicator of what makes one patient more "curable" than another, Dr. Mike McCune, chief of experimental medicine at the University of California, San Francisco, speculated that the secret might be that some people have an "imbalanced" immune response that defeats the wily virus: They produce antibodies that neutralize H.I.V., but don't get inflammation, which increases CD4 cells.

That reaction may be more common in babies, he speculated, because their immune responses are muted in the womb so they don't attack their mothers' cells.

And even the Mississippi baby had progenitors, he said. Since the 1990s, about 20 babies who supposedly cleared the virus have been reported in medical journals, but each case had doubters.

The Mississippi baby is more convincing because that case was "much better studied," Dr. McCune said.

Another hypothesis, he said, is that some patients are "cured" because they got weaker virus.

By deliberately infecting monkeys, it has been shown that less-robust viral strains are controllable with drugs.

"But," Dr. McCune added, "as you can imagine, no one wants to do that study in humans."



www.aegis.org