Two HIV-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 said.
The patients’ success echoes that of Seattle native 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 HIV.
The Boston cases, as with Brown’s, are of no practical use to the 34 million people who have HIV but neither blood cancer nor access to premier cancer-treatment hospitals.
But AIDS experts find the Boston cases exciting nonetheless because they are another step in the long and so-far-fruitless search for a cure. They offer encouragement to future projects to genetically re-engineer infected patients’ cells to be infection-resistant.
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At least two teams — including one at Seattle’s Fred Hutchinson Cancer Research Center — are experimenting with variants on this idea, said Dr. Steven Deeks, an AIDS researcher at the University of California, San Francisco.
Dr. Françoise Barré-Sinoussi, a discoverer of the virus that causes AIDS and the president of the International AIDS Society, 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 Wednesday in Kuala Lumpur, Malaysia.
Brown is sometimes referred to as the “first HIV 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 HIV can live relatively normal lives by taking a daily antiretroviral cocktail.
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 Brown.
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, Henrich said.
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.
His 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 HIV.
The donors for the Boston patients did not have the mutation.
Unlike 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,” 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, Henrich said.
Because only the old cells were infected with HIV, 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 HIV, he said.
It is known to prevent retroviruses such as HIV 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 HIV or antibodies to it were found, before Henrich and his research partner, 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 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,” Henrich said.
That distinguishes them from Brown, who has survived virus-free for more than five years but still has weakness and pain from his grueling anti-cancer 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.
Material from The Seattle Times archive is included in this report.