HIV Eradication Moves One Small Step Closer as Stem Cell Transplant Findings Titillate

Myles Helfand

By now, every soul in HIV care likely knows about the "Berlin patient." Similarly, we know that the extraordinary results of that case are extremely challenging to successfully replicate.

But what if the stem cell transplant that functionally cured Timothy Brown was made just a little bit easier? Say, by removing the need to find a matching donor who lacked the delta 32 mutation that appears to effectively render a person immune from infection with CCR5-tropic HIV?

Such is the recipe that Timothy Henrich and Daniel Kuritzkes of Brigham and Women's Hospital in Boston, along with a host of colleagues, sought to cook up for a pair of their patients with very long-term HIV infection (which has been tempered by successful combination antiretroviral therapy) and Stage IV Hodgkin lymphoma for whom an autologous hematopoietic stem cell transplant (HSCT) had previously been attempted. Their results were actually presented last year at the International AIDS Conference (where they received a surprisingly small amount of attention), but were just published in the June 1 issue of the Journal of Infectious Diseases.

The two "Boston patients," let's boringly call them, underwent allogeneic HSCT -- the same procedure Timothy Brown received -- but with a key difference: The stem cell donors in this case were heterozygous for the CCR5-delta 32 mutation (they had wild-type CCR5+ cells), meaning the patients' CD4+ cells still had CCR5 receptors after the procedure, leaving them susceptible to infection by any active virus that may have been lingering post-transplant.

They also -- and this may or may not be critical, we can't be sure yet -- remained on their antiretroviral therapy throughout the treatment process. In fact, as of these published results, they were still taking antiretroviral therapy long after the HSCT (about 3.5 years after in one case; nearly two years in the other).

And now, here we are:

• Proviral HIV-1 DNA levels in peripheral blood mononuclear cells dropped from 100-150 at the time of HSCT to zero within 300 days of the procedure.
• Similarly, there was no trace of HIV-1 DNA in purified CD4+ cells two-plus years post procedure -- nor was there any sign of HIV-1 p24 antigen.
• Ultrasensitive, single-copy HIV-1 RNA assays found nothing at any time point in either patient post procedure.

There's still much research to be done here before we can call these people cured, of course. For one thing, as David Margolis noted in Journal Watch HIV/AIDS Clinical Care last week, not every immunological crevice of these two brave study participants has yet been explored for traces of HIV. For another, there's the small matter of them still being on antiretroviral therapy. Both of these limitations will be explored in further study.

Similarly, the immediate clinical relevance of these findings is all but nonexistent; allogeneic HSCT remains a costly and extremely risky procedure we reserve for only the most intractable cancer cases. But there is at least one important takeaway message we can deliver to all of our patients who may ask about this story (or to whom we choose to tell it), and it lies within the study authors' own conclusion:

"[O]ur findings confirm that RIC allogeneic HSCT is a safe treatment in HIV-infected patients with hematologic malignancies whose infection is well controlled by cART."

That little chunk of text I bolded is the base of the fountain from which virtually all of our recent "cure" successes flow: Above all things, to thine own antiretroviral therapy be true. We need to ensure our patients are emotionally ready for treatment; start it and adhere to it; and maintain an open dialog with us about their successes, their failures, their hopes and their concerns. When that happens, anything is possible.

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Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.

Follow Myles on Twitter: @MylesatTheBody.

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