Published: July 3, 2013
Two H.I.V.-infected patients in Boston who had bone-marrow transplants for blood cancers have apparently been virus-free for weeks since their antiretroviral drugs were stopped, researchers at an international AIDS conference announced Wednesday.
The patients’ success echoes that of Timothy Ray Brown, the famous “Berlin patient” who has shown no signs of resurgent virus in the five years since he got a bone-marrow transplant from a donor with a rare mutation conferring resistance to H.I.V.
The Boston cases, as with Mr. Brown’s, are of no practical use to the 34 million people in the world who have H.I.V. but neither blood cancer or access to premier cancer-treatment hospitals.
But AIDS experts still find the Boston cases exciting because they are another step in the long and so-far-fruitless search for a cure. They offer encouragement to ambitious future projects to genetically re-engineer infected patients’ cells to be infection-resistant. At least two teams are already experimenting with variants on this idea, said Dr. Steven G. Deeks, an AIDs researcher at the University of California at San Francisco Medical School.
Dr. Françoise Barré-Sinoussi, a discoverer of the virus that causes AIDS and the president of the International AIDS Society meeting now in Kuala Lumpur, Malaysia, called the findings about the Boston patients “very interesting and very encouraging.” The announcement about the cases was made at the society’s annual conference.
Mr. Brown is sometimes referred to as the “first H.I.V. cure.”
But there are important differences between his case and those of the Boston patients. For example, no AIDS expert, including the doctors from Brigham and Women’s Hospital in Boston following the two patients, is using the word “cured” to describe their status.
The technique used on them involves severely weakening the immune system before a marrow transplant. It is so dangerous that it is unethical to perform it on anyone not already at risk of dying from cancer, especially because most people with H.I.V. can live relatively normal lives by taking a daily antiretroviral cocktail.
“But we cannot speak about ‘cure,' ” she added. “The follow-up has been very short.”
One patient stopped taking antiretroviral drugs seven weeks ago. For the other, it has been 15 weeks. No virus or antibodies to the virus have been found in their blood or other tissues since.
Normally, when a patient stops the drugs, the virus bounces back in less than a month, but each person is different.
“It could come back in a week, or in six months,” said Dr. Timothy Henrich, a doctor overseeing the two patients. “Only time will tell.”
The process the two patients underwent is risky – a third patient in the study died when his cancer returned – but somewhat less so than the procedure done on Mr. Brown.
Mr. Brown had leukemia. The three Boston patients had lymphoma.
The Boston patients’ bone marrow, where new blood cells are made, was only partially destroyed by drugs before they were given new marrow from matching donors — a process that carries a 15 to 20 percent risk of death, Dr. Henrich said.
Mr. Brown’s marrow was completely obliterated by drugs and whole-body radiation, a procedure that kills 40 percent of the patients, and he had it done twice.
Mr. Brown’s new marrow came from a donor who was a close genetic match and had a rare mutation that makes a person virtually impervious to infection with H.I.V.
The mutation, known as delta 32, creates CD4 cells — the white blood cells that the virus attacks — lacking a CCR5 surface receptor, the “door” that the virus uses to enter the cell.
The donors for the Boston patients did not have the delta 32 mutation.
Unlike Mr. Brown, the Boston patients stayed on antiretroviral therapy throughout the lengthy transplant process and for years afterward. The drugs prevent the virus from replicating itself.
“The idea was to protect the new donor cells from becoming infected,” Dr. Henrich explained.
During that time, in a phenomenon known as graft-versus-host disease, the new cells were attacking their old, chemotherapy-weakened counterparts and clearing them from the body, a process that takes about nine months, Dr. Henrich said.
Because only the old cells were infected with H.I.V., the hope was that graft-versus-host disease would “mop up” all the viral reservoirs.
But runaway graft-versus-host disease can be fatal, so the two patients were intermittently on and off immunosuppressive drugs and steroids to control it.
One immunosuppressive drug, sirolimus, may also have helped kill off H.I.V., he said.
It is known to prevent retroviruses like H.I.V. from replicating.
The two patients had transplants between two and five years ago. They had months of tests on their blood and tissues to make sure no H.I.V. or antibodies to it were found, before Dr. Henrich and his research partner, Dr. Daniel Kuritzkes, proposed stopping the antiretroviral treatment.
For such tests, doctors remove immune cells and “activate” them with chemicals to make them reproduce. If any virus is hiding in the cells’ DNA, it is “spit out” and can be detected.
But doctors can never be sure that they have tested all the reservoirs where dormant virus might hide. It is relatively easy, for example, to sample rectal but not brain tissue.
Since the patients stopped taking antiretrovirals, they “feel great and are leading completely normal lives,” Dr. Henrich said.
That distinguishes them from Mr. Brown, who has survived virus-free for more than five years but still has weakness and pain from his grueling anticancer regimen.
AIDS specialists are interested in the Boston patients because they offer new insights into how the immune system can be used to attack the virus.
Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said it was “conceivable and maybe even likely” that their H.I.V. was permanently gone.
If so, he said, it would show that it is not necessary to find a matching donor who also had the delta-32 mutation.
Dr. Deeks, the AIDS researcher in California, said the cases raise the question of when to say an H.I.V. patient has been “cured.”
“Should we wait six months to see if the virus rebounds?” he asked. “Or will we have to wait up to five years, as oncologists tend to do with cancer?”
Dr. Barré-Sinoussi said she might eventually prefer to adopt the term oncologists use: “in remission.”