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    bottles-gentaur-antibodiesTwo patients have been taken off their HIV drugs after bone-marrow transplants seemed to clear the virus from their bodies, doctors report.

    One of the patients has spent nearly four months without taking medication with no sign of the virus returning.

    The team at Brigham and Women's Hospital, in the US, caution that it is far too soon to talk about a cure as the virus could return at any point. The findings were presented at the International Aids Society Conference.

    It is difficult to get rid of an HIV infection because it hides inside human DNA, forming untouchable "reservoirs" in body. Anti-retroviral drugs keep the virus in check within the bloodstream - but when the drugs stop, the virus comes back.

    The two men, who have not been identified, had lived with HIV for about 30 years. They both developed a cancer, lymphoma, which required a bone-marrow transplant.

    Bone marrow is where new blood cells are made and it is thought to be a major reservoir for HIV. After the transplant, there was no detectable HIV in the blood for two years in one patient and four in the other.

    It is far too early to call this a cure for HIV. And even if it was a cure, it wouldn't be a very good one.

    It is very expensive and often leads to "graft-v-host" disease. There is a 15-20% mortality rate within the first few years after the transplant.

    This occurs when new immune cells produced by the graft treat the rest of the body as foreign and attack it.

    The two patients in this study have replaced their regimen of anti-retroviral drugs, with those to suppress the immune system.

    The procedure was carried out in these patients only because they had cancer that needed to be treated. The real value of this research for the majority of people with HIV will come from a deeper understanding of the virus and HIV reservoirs. The pair came off their anti-retroviral drugs earlier this year.

    One has gone 15 weeks, and the other seven, since stopping treatment, and no signs of the virus have been detected so far.

    Dr Timothy Henrich told the BBC the results were exciting. But he added: "We have not demonstrated cure, we're going to need longer follow-up.

    "What we can say is if the virus does stay away for a year or even two years after we stopped the treatment, that the chances of the virus rebounding are going to be extremely low. "It's much too early at this point to use the C-word [cure]."

    It is thought that the transplanted bone marrow was initially protected from infection by the course of anti-retrovirals. Meanwhile the transplant also attacked the remaining bone marrow, which was harbouring the virus.

    However Dr Henrich cautioned that the virus could be still be hiding inside brain tissue or the gastrointestinal track.

    "If the virus does return, it would suggest that these other sites are an important reservoir of infectious virus and new approaches to measuring the reservoir at relevant sites will be needed to guide the development of HIV curative strategies," he said.

    The two US cases both received bone marrow from normal donors. There was also a report of an HIV cure in a baby born in Mississippi, US. She was treated with anti-retroviral drugs at birth so it is thought the virus was cleared from the body before reservoirs were established.

    Dr Michael Brady, the medical director of the Terrence Higgins Trust, said: "It is too early to know whether HIV has been eradicated from these men's bodies or whether it might return.

    Doctors say it is far too soon to talk about a cure for HIV, as James Gallagher reports "However, the case suggests that what happened to Timothy Brown, the Berlin Patient was perhaps not a one-off.

    "A bone marrow transplant is a complex and expensive procedure, which comes with significant risks. "For most people with HIV, it would be more dangerous to undergo a transplant than to continue managing the virus with daily medication.

    "So while this is by no means a workable cure, it does give researchers another signpost in the direction of one."

    The head of the Foundation for AIDS Research, Kevin Frost, said: "These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy.

    "While stem-cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV."

     

    Published in News
    Thursday, 04 July 2013 10:31

    Stem-cell transplants may purge HIV

    Daniel-KuritzkeTwo men with HIV may have been cured after they received stem-cell transplants to treat the blood cancer lymphoma, their doctors announced today at the International AIDS Society Conference in Kuala Lumpur.

    One of the men received stem-cell transplants to replace his blood-cell-producing bone marrow about three years ago, and the other five years ago. Their regimens were similar to one used on Timothy Ray Brown, the 'Berlin patient' who has been living HIV-free for six years and is the only adult to have been declared cured of HIV. Last July, doctors announced that the two men — the ‘Boston patients’ — appeared to be living without detectable levels of HIV in their blood, but they were still taking antiretroviral medications at that time.

    Timothy Henrich, an HIV specialist at Brigham and Women’s Hospital in Boston, Massachusetts, who helped to treat the men, says that they have now stopped their antiretroviral treatments with no ill effects. One has been off medication for 15 weeks and the other for seven. Neither has any trace of HIV DNA or RNA in his blood, Henrich says.

    If the men stay healthy, they would be the third and fourth patients ever to be cured of HIV, after Brown and a baby in Mississippi who received antiretroviral therapy soon after birth.

    But Henrich and Daniel Kuritzkes, a colleague at Brigham who also worked with the men, caution that it is still too early know whether or not the Boston patients have been cured. For that, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in 'reservoirs' — parts of the men’s bodies, such as their brain or gut, that can harbour the virus for decades.

    “We’re being very careful not to say that these patients are cured,” Kuritzkes says. “But the findings to date are very encouraging.”

    HIV researcher Steven Deeks of the University of California, San Francisco, says that doctors might need to wait at least two years before declaring that a cure has been achieved. “Any evidence that we might be able to cure HIV infection remains a major advance,” Deeks says. But, he adds, “there have been cases of patients who took many weeks off therapy before the virus took off”.

    Exciting news

    Still, researchers and doctors are excited about the news, especially because the Boston patients’ treatment differed from the Berlin patient’s regimen in one key way. Brown was given stem cells that were predisposed to resist HIV infection, because the donor happened to have a mutated version of a key protein — CCR5 — that is needed for HIV to infect cells. So Brown’s transplant was akin to gene therapy with HIV-resistant cells.

    But the Boston patients received stem cells without the protective mutation. The transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. Their doctors think that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient’s own cells — may have then wiped out the patients’ HIV reservoirs, potentially curing the men.

    Transplant specialist Christine Durand of Johns Hopkins University School of Medicine in Baltimore, Maryland, says that the case of the Boston patients may show that current antiretroviral drugs are powerful enough, on their own, to protect the transplanted cells. “If cure has been achieved in the Boston patients, then it was the antiretroviral therapy, not gene therapy, that protected the donor cells,” she says.

    The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to be used more generally because the risks from transplants are high. Durand says that Johns Hopkins is now revising its transplant procedures to keep people with both cancer and HIV on antiretroviral drugs during the transplant regimen.

    Separately, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, based in Silver Spring, Maryland, is trying to replicate the Berlin patient’s cure by giving CCR5-mutated HIV-resistant blood from umbilical cords to children and adults with HIV and cancer. 

    Everyone with HIV could benefit from this work, researchers say, because it could yield valuable information about how to eliminate the HIV reservoir.

    “We are still a long way off from a viable cure option for most patients,” Durand says. “But every step counts, and these cases can teach us important lessons.”

     

    Published in News