71) Two Patients HIV-Free After Stem Cell Treatment --- medpagetoday.com

Two Patients HIV-Free After Stem Cell Treatment

(source: medpagetoday.com, July 3, 2013)

KUALA LUMPUR -- Two HIV-positive men who got a stem cell transplant to treat blood cancers have now been off antiretroviral drugs for several weeks without evidence of the virus rebounding, a researcher said here.

The apparent HIV remissions are exciting developments, but it is too early to say the men have been cured, according to Timothy Henrich, MD, of Brigham and Women's Hospital in Boston.

"It is possible that the virus could come back next week," Henrich told reporters before his late-breaker presentation at the 7th International AIDS Society meeting on HIV pathogenesis, treatment, and prevention.

But researchers have been unable to find evidence of HIV replication or of HIV DNA integrated into inactive immune cells, although the men have been off HIV therapy for 8 and 15 weeks, respectively, Henrich reported.

If that state persists, he said, it might offer clues to a more widely applicable approach to inducing HIV remission, since stem cell transplant is "not a practical strategy" to cure the 34 million people with HIV worldwide.

Outside experts also cautioned against hyping the findings.

"The next step is to confirm this in larger numbers," said Sharon Lewin, MD, of Monash University in Melbourne, Australia. That might be possible because stem cell transplants are performed relatively often around the world, some of them in people with HIV.

But she echoed Henrich's view that stem cell transplant will not be widely useful in curing HIV, if only because of the expense and risk of the procedure.

But, she told reporters, such cases are "absolutely instrumental in moving the science forward."

Indeed, Henrich said, so far investigators don't know what aspect of the stem cell transplant and subsequent therapy led to the disappearance of the virus.

The best guess at the moment, Henrich said, is that graft-versus-host disease -- a common sequel to allogeneic stem cell transplant -- eliminated HIV-bearing host cells while the donor cells were protected from infection by antiretroviral therapy.

The finding is reminiscent of the case of Timothy Brown, the "Berlin patient," who was the first person to have an apparently curative stem cell transplant.

But in that case, doctors sought a donor whose immune cells carried a mutation -- the delta32 variant of the CCR5 gene -- that rendered them resistant to HIV infection.

Brown had what is called myoablative conditioning to completely destroy his own immune system before getting the donor cells and was not on antiretroviral drugs after the transplant.

In the 2 cases in Boston, both men had minimal conditioning with chemotherapeutic drugs, so their own immune systems were not completely destroyed. And they got donor cells that -- in principle -- were susceptible to HIV.

During and after the transplant, both patients remained on antiretroviral therapy for 2.7 and 4.5 years of follow-up before stopping therapy, Henrich said.

It was only recently -- after consultation with ethics boards, the patients themselves, and their doctors -- that Henrich and colleagues "felt justified" in stopping the anti-HIV medications.

The decision to undertake an "analytical treatment interruption" was based on the continuing inability to find HIV in the two men, Henrich said.

Because of the effectiveness of current anti-HIV therapy, the investigators thought stopping treatment entailed "minimal risk" to the patients, senior investigator Dan Kuritzkes, MD, also of Brigham and Women's, told MedPage Today.

Such treatment interruptions have been tested several times in patients who have suppressed virus under anti-retroviral therapy, and usually result in HIV rebound within days.

But there are several cases -- including a cohort in France -- where such interruptions have led to durable control of the virus without the need to resume anti-HIV therapy.

And U.S. researchers are following up the case of an HIV-positive infant, treated within hours of birth, who currently has no evidence of the virus although she was lost to follow-up and did not receive treatment for several months.

In the months and years to come, Lewin said, it's extremely likely that more such individual cases of HIV remission will be found, which might raise "false hope" for a cure.

"We want a much larger, scalable cure" to treat 34 million people, she said, "and that is going to be quite a challenge."