Two men known only as the “Boston patients” have both stopped taking their anti-HIV medications following transplants of bone-marrow stem cells that appear to have banished the virus from their bodies.

They are the latest in a series of people with HIV who appear to be practically rid of the virus – although researchers warn it is too soon to declare them cured. Earlier this year, reports emerged of an infant and a group of 14 adults who all experienced functional HIV cures, meaning that although their bodies still had traces of the virus, it was no longer active.

So far, these functional cures have all been attributed to very early treatment with antiretroviral drugs, before the virus could take hold. The Boston patients, in contrast, are free of the virus thanks to a combination of a bone marrow transplant plus continuing antiretroviral drugs to stop newly donated immune cells from being infected.

Tim Henrich of Brigham and Women’s Hospital in Boston, Massachusetts, who led an investigation into the men’s condition, says that the men remain virus-free between three and four years after their transplants, even though they gave up taking antiretrovirals 15 and 7 weeks ago respectively. He presented the latest results today in Kuala Lumpur, Malaysia, at the annual meeting of the International AIDS Society.


Cure not confirmed

“While these results are exciting, they do not yet indicate that the men have been cured,” says Henrich. “Long-term follow-up of at least one year will be required to understand the full impact of a bone-marrow transplant on HIV persistence.”

Both of the Boston men were already HIV-positive when they were diagnosed with Hodgkin’s lymphoma, a type of blood cancer. They both had standard chemotherapy to kill their native blood cells before undergoing a bone-marrow transplant from a donor to repopulate their blood. Until recently, both men also continued to take anti-HIV drugs in an effort to prevent any residual virus from infecting their “new” immune systems.

“Since coming off antiretroviral therapy this spring, the men continue to have no detectable HIV DNA or RNA in their blood,” says Henrich.

There is one previous case of an HIV-positive individual being “cured” following a bone marrow transplant – the “Berlin patient”, Timothy Ray Brown. But he owed his good fortune to the fact that his new bone marrow came from a donor whose blood cells had a mutated version of a protein called CCR5. HIV exploits the normal version of this protein to enter cells, but cannot do the same with the mutated protein. So when the donated cells repopulated Brown’s blood, they were all by default resistant to HIV.

The Boston patients, by contrast, received bone marrow from donors without this mutation. Henrich hopes to find out how the resulting blood cells remained uninfected despite this. He suspects that continued antiretroviral drug treatment was crucial.

Possible return

“Our patients remained on antiretroviral therapy throughout transplantation, and donor cells appear to be protected from infections during engraftment and replacement of host cells,” he says. “But it’s possible the virus could return in both of our patients in the coming weeks, months or even years.”

“The result is very encouraging, but we need longer-term follow-up,” says Françoise Barré-Sinoussi of the Pasteur Institute in Paris, France, who shared the 2008 Nobel prize in medicine for co-discovering HIV, and who was not involved in the Boston study.

“We need to understand better why these patients have undetectable virus,” she says. “All the mechanisms need to be clarified, and then we can expect to develop another strategy for other patients that might not involve a transplant.”

At the same symposium, Sharon Lewin of the Alfred Hospital in Melbourne and her colleagues revealed that a drug called entinostat has potential in the quest for an HIV cure. At present, all HIV-positive people must take antiretroviral drugs for life because the virus can hide in the body and re-emerge if treatment is halted. Entinostat, an anti-cancer drug, is the latest of a family of drugs that could lead to a full cure by reviving dormant virus and flushing it out into the bloodstream, where it can be killed by standard antiretroviral drugs.