July 28, 2012
New Stem Cell Transplant Cases Encouraging, but Cure Buzz May be Premature
by Tim Horn
Have two HIV-positive stem cell transplant patients been cured of their infection? Several mainstream media headlines following a presentation by Boston researchers on Thursday, July 26, at the XIX International AIDS Conference (AIDS 2012) suggest they have. But while the case reports are intriguing and encouraging—both patients have undetectable blood- and cell-based virus and have been experiencing reductions in their HIV antibody levels following chemotherapy, stem cell transplants and while remaining on antiretroviral therapy following cancer diagnoses—references to a cure may be premature ("Two More Patients HIV-Free After Bone Marrow Transplants" reads an ABC News headline).
The latest case reports were reported by Timothy Henrich, MD, an infectious disease physician at Brigham and Women’s Hospital in Boston and his colleagues. He began by referencing the familiar case of Timothy Brown, colloquially known as the “Berlin Patient,” who was cured of his leukemia and HIV infection following high-dose chemotherapy and a stem cell transplant from a donor whose CD4 cells lacked the CCR5 receptor needed by HIV to establish infection.
Scientists hope to duplicate Brown’s outcome in other patients—notably those with certain cancers who require grueling stem cell transplants to save their lives—using CCR5-deficient stem cells from adult donors, cord blood samples and gene modification strategies (using zinc finger nucleases, for example).
Questions, however, still remain surrounding Brown’s case, notably: To what extent did his pre-transplant chemotherapy contribute to the destruction of the reservoirs of HIV in his body? Does graft-versus-host disease—the targeting of donors’ foreign immune system cells by transplant patients’ own cells—aid in eradicating reproducible virus?
Henrich’s team, in turn, wanted to explore the long-term effects of pre-conditioning chemotherapy and stem cell transplants in patients who didn’t receive cells from donors with HIV-susceptible cells. They focused on two Brigham and Williams patients who were living with HIV and underwent transplants for lymphoma-related cancers. But unlike Brown, they received transplants using cells expected to produce CD4s carrying the CCR5 receptor; they also received less-intensive chemotherapeutic pre-conditioning than Brown, so that they could remain on their antiretrovirals during and after the transplant process.
Both patients remained on ARVs while undergoing transplants—one was receiving Atripla (efavirenz/tenofovir/emtricitabine) the other was receiving Isentress (raltegravir) plus Truvada (tenofovir plus entrictabine)—and both were treated with immune-suppressive drugs following their transplants after experiencing grant-versus-host disease.
Looking back at blood samples collected from the patients during post-transplant follow up—one patient had roughly two years of samples available; the second had roughly three-and-a-half years of follow-up samples available—Henrich and his colleagues made a number of encouraging discoveries.
Using highly sensitive viral load technology, levels of replication-competent HIV—if it is still present—eventually became too low to be accurately measured, compared with what is typically seen in people receiving antiretroviral treatment ((less than a half copy per milliliter of blood plasma versus 1 to 2 copies per milliliter of blood plasma, respectively).
As for HIV-DNA inside cells in blood samples, Henrich and his group noted that genetic material was detected in the months following stem cell transplantation. But by day 200 in one patient and day 300 in the other, HIV-DNA became undetectable. In fact, efforts to “grow out” the virus in samples from the patients at day 1,266 and 652, respectively, proved fruitless.
While HIV antibodies are still detectable in both patients, substantial decreases in antibody levels began approximately 200 days following their transplants.
Are these patients cured of their HIV infection? While Henrich suggested the data are encouraging, noting the “substantial and sustained reduction in the HIV reservoir” and that the “declining HIV-specific antibody levels provide further evidence for minimal persistence of HIV antigen” are important findings, some key pieces of the puzzle are still missing.
Unlike Brown, who has remained off HIV treatment for more than five years and has produced tissue samples devoid of replication-competent HIV, the two patients under Henrich’s care have yet to initiate an antiretroviral treatment interruption and do not yet have tissue samples available. These are necessary, Henrich explained, “to fully assess the extent of HIV reservoir reduction after stem cell transplantation.”
“We’re being very careful to refer to our patients as not being functionally cured,” added Daniel Kuritzes, MD, a Harvard Medical School researcher who has been working alongside Henrich.
Search: hiv, cure, stem cell transplant, hsct, boston, brigham and williams, henrich, reservoirs, graft-versus-host, gvhd, antiretrovirals, treatment, eradication, aids 2012
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comments 16 - 20 (of 20 total)
keith, Dublin, 2012-07-29 10:45:02
I still argue that if these two people are declared cured and or the two in europe getting cord blood transplant then this disease is curable.
It may not be easily curable but it will be come curable
Melanie Thompson, Atlanta, 2012-07-28 15:27:50
Excellent column, Tim. Balanced and accurate, as always. It's too soon to use the word "cure" for these two patients who are still on ART. There was much more caution in the case of Tiimothy Brown. Encouraging and interesting - but not a cure...yet. Others who have had stem cell transplants in the past have not been cured, so we need to wait for the rest of the evidence. As usual, the doctors are more cautious than (most) media. Good job!
jay, us, 2012-07-28 15:18:43
Lord I just pray for a second chance at having an HIV free life this virus is nothing less than a monster that needs to be destroyed
Keith, , 2012-07-28 11:25:06
While it maybe premature it is very encouraging.
I find these types of test much more helpful than the millions of phase 1 tests been done around the world.
I am also encouraged and hopeful that the two cord blood tests been done in europe will work.
The two people mentioned in the article above should be taken off ARVs and tested. If the disease doesnt bounce back then as far as I am concerned HIV is curable.
We will know within a year
Andy, , 2012-07-28 10:52:53
comments 16 - 20 (of 20 total)
What gives with the pessimism? It's still not like this procedure is desirable or economical, but it is further proof of concept. Just call a cure a cure a cure, and stop splitting hairs about whether or not they've fulfilled X or Y criteria. Heck, I'll take this over the "suicide as a prevention" paradigm that we're moving towards with "MSM can use home HIV tests for prevention". What about the Margolis study? Did this magazine change ownership, cuz its message seems to have changed.
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