Dr. Daniel Kuritzkes of Brigham and Women’s Hospital, speaking at an AIDS research conference in Kuala Lumpur, Malaysia, where his team is announcing details about two cancer patients whose treatment appears to have eradicated their HIV infections.
Two men who had grueling bone marrow treatments for cancer are enjoying a happy side effect: They appear free of the AIDS virus, researchers reported on Wednesday.
The doctors are not quite ready to call it a cure, but they say the men have stopped taking HIV drugs and have remained free of the virus for almost four months in one case and almost two months in another.
“While these results are exciting, they do not yet indicate that the men have been cured,” says Dr. Timothy Henrich of Brigham and Women’s Hospital and Harvard Medical School in Boston.
The cases of the two men, who don’t want their names released, were first reported at an international AIDS conference in Washington last July. Henrich, Dr.Daniel Kuritzkes and colleagues had actively looked for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants.
They wanted to replicate the case of Timothy Brown, also known as the "Berlin patient," who was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells, and he remains free of the virus more than five years later.
They found three patients who had remained on HIV regimens while undergoing bone marrow transplants, which are designed to destroy the cancer and replace diseased blood and immune systems with healthy ones from donors.
The patients' own bone marrow is destroyed, usually with chemotherapy or radiation, and replaced with a tissue-matched transplant from a donor.
Henrich said at the time that the AIDS cocktails likely protected the new transplanted bone marrow from infection.
One patient is HIV-free nearly three years later, and the other more than four years later. Each made the choice to discontinue his AIDS drugs a few weeks ago.
Now there is still no evidence the virus is anywhere in their bodies, Henrich says. He’ll report his findings to a meeting of the International AIDS Society in Malaysia.
“Up to week 14 for both patients, we continue to be unable to detect (HIV) DNA in their cells or virus in their blood,” Henrich says.
“We looked very deeply this time -- much more deeply than last time.” They looked in the immune cells that HIV attacks, especially the CD4 and CD8 T-cells. They also took samples of rectal tissue from one patient to make sure no virus was hiding there. The one place they didn’t look was in the brain. “We didn’t feel the risk of that was justified,” Henrich says.
The patients will get weekly blood tests for at least a year or more, says Henrich. “We don’t even know where some of the HIV might be hiding,” he says.
The case raises a big question that some AIDS specialists never dreamed they would be asking: When do you declare a cure?
"There never is an 'aha' moment when you suddenly can declare a cure," says Kevin Robert Frost, CEO of thee Foundation for AIDS Research (amFAR), which helped pay for the study. "it is impossible to prove the absence of something."
The human immunodeficiency virus that causes AIDS is transmitted sexually, in blood, on infected needles, at birth and in breast milk.
HIV drugs called antiretroviral therapy can keep the virus suppressed to such low levels that patients are healthy and their immune systems are not damaged. People taking the drugs are also less likely to infect someone else, and studies show that uninfected people who take them are much less likely to become infected.
So doctors believe the drugs can stop the virus from infecting cells and, perhaps, from hiding out in the body. But people who are infected and who stop taking their drugs almost always have the virus come back at some point, so it does lurk in what are known as reservoirs.
Henrich says doctors have been debating when and if to declare the patients cured. Timothy Brown, the Berlin patient, says he is. “What is the definition of a cure? “ Henrich asked. “Even with the Berlin patient, who is five years out, it could come back, although the chances are very small.”
A third patient who also seemed HIV-free died when his lymphoma returned, Henrich said. It’s clear this isn’t a treatment for the average HIV patient, but it does show it may be possible to eradicate the virus. It also suggests that HIV patients who do get leukemia or lymphoma should stay on their HIV drugs during treatment.
Then there is the widely reported case of a baby in Mississippi whose HIV infection disappeared after unusually early and aggressive drug treatment. “She’s doing quite well,” says Dr. Hannah Gay of the University of Mississippi Medical Center, who treated the child.
The child, who lives in rural Mississippi, is now 3 years old and still has no evidence of active HIV infection. She was born to a mother who didn’t know until right before she gave birth that she had HIV, and when the child was diagnosed with the virus, Dr. Gay decided on an unusual course of aggressive treatment.
Gay's colleagues reported at another AIDS meeting in March that the treatment appears to have eradicated what’s known as “replication-capable” virus, although some tests do show evidence of HIV in the child’s body.
“We still don’t know exactly when to declare a cure and that's the case even with the Berlin patient,” Gay told NBC News.
“Our baby is doing great. It is our intention to keep following her closely. We know that … there is the possibility she has some cells hidden there that are infected with replication-competent virus that somewhere down the line could come back out. We are aware that is a possibility,” Gay added.
Frost says it may change the direction of research. Timothy Brown was given transplants of bone marrow cells from a patient with a mutation in a gene called CCR5, which makes people resistant to HIV infection. But the latest two patients got ordinary cells.
"Most people thought that was a critical component of what had been achieved in the Berlin patient. I think this changes the game," Frost told NBC News.
Henrich says it is possible that transplanted immune system cells destroyed any remaining HIV-infected cells as part of their normal and expected scavenging of alien cells -- which would include any of the patients' own immune cells left after the pre-transplant destruction.
Frost said he had not heard of any other patient going as long at 15 weeks without HIV drugs without the virus coming back. But he is nonetheless cautious. "My sense is we going to be at least a year out before anybody is going to be prepared to make claims about what these cases really mean," he says. "You want to be at least a year out before you would consider declaring a victory."
“Whatever the outcome, we will have learned more about what it will take to cure HIV," added amfAR research director Dr. Rowena Johnston.
First published July 3 2013, 1:27 AM