An End to HIV: HIV Remove from Cultured Cells

https://i0.wp.com/292fc373eb1b8428f75b-7f75e5eb51943043279413a54aaa858a.r38.cf3.rackcdn.com/health-fitness_01_temp-1357384489-50e80b29-620x348.jpgAt the closing ceremony of the AIDS 2014 conference a few weeks ago in Melbourne, Australia, many of the speakers – including longtime AIDS researcher and International AIDS Society Presidential Award winner Eric Goosby – told of how utterly terrifying the disease seemed 30 years ago. And while that fear is not gone, it has since diminished, replaced by and large with a sense of hope that the disease will be eradicated.

According to UNAIDS – the Joint United Nations Programme on HIV/AIDS, which is dedicated to destroying the disease by 2030 – the medical community has learned much in the past few years and stands a good chance at accomplishing this goal. And with new advances being announced every few months, hopes for a world in which this terrible disease no longer exists all seem firmly on track.

UNAIDSConsider this latest development, which comes from the Temple University School of Medicine in Philadelphia. Here, researchers have discovered how to permanently extricate HIV-1 from human cells, effectively curing a patient of the disease. Combined with new vaccines that have shown the ability to block infection (and in some cases, even reverse it), this news may yet be reason for even greater hope.

One of the main issues in the treatment of HIV-1 is not simply that it is expensive, but that antiretroviral therapy have terrible side effects that can speed up diseases more commonly associated with aging or can cause co-infections, such as Hepatitis C, to become worse.  Added to this is that HIV is a tricky and tenacious disease that becomes part of a patient’s DNA, making it virtually impossible to eradicate.

https://i1.wp.com/images.gizmag.com/gallery_lrg/scientistseliminatehivfromhumancells.jpgHowever, researchers from Temple University School of Medicine have found a way to cut the infected genes out, potentially eradicating the virus for good and negating the need for lifelong ARV treatment. The technique uses a DNA-snipping enzyme, a nuclease, and a targeting RNA strand to hunt down the genome and cuts the HIV-1 DNA from it. The cell is able to repair its own genomes, essentially sewing itself together again, only now HIV-free.

This treatment will work in varied cell types such as the T-cells and monocytic cells that harbor HIV. In designing the molecular tools, researchers chose nucleotide sequences that do not appear in any coding sequences of human DNA to avoid what they call off-target effects, where patient’s cells or own DNA might be damaged. The technique may also be applicable against many other viruses.

There are still serious hurdles, like how to get the treatment into each, individual cell. Also, HIV-1 is known for mutations, and every patient has their own viral sequence. This means that there can be no single, prescriptive treatment for it. However, another potential upside is that there is the chance this may be used not simply as a treatment but also a vaccine as cells containing the nuclease-RNA combination do not acquire the HIV infection.

https://i0.wp.com/www.templehealth.org/AssetMgmt/getImage.aspxDr. Kamel Khalili, Professor and Chair of the Department of Neuroscience at Temple, calls it an “important step” towards the eradication of AIDS, though it is still years away from the clinical stage. As he put it:

We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it.

Though it is not the one-shot breakthrough many have been hoping for, this enzyme-based treatment is another step along the long road towards the end of HIV and another nail in its coffin. As long as treatments exist that are not only able to treat and block, but also fight the disease, there is much reason for hope.

And be sure to check out this video from Temple University, where Dr. Khalili explains the medical breakthrough:


Sources:
gizmag.com, templehealth.org

The End of HIV: Two Men Cleared After Marrow Transplant

hiv-virus-cuFor decades, bone marrow transplants have been used for the treatment of cancer, particularly lymphoma, leukemia, and multiple myeloma. However, after three years of receiving transplants, two Australian men who were previously diagnosed with HIV have shown no signs of the AIDS virus. Moreover, one of the patient’s is the first recorded case of clearing the virus without the presence of a rare anti-HIV gene in the donor marrow.

The two patients, a 53-year-old and 47-year-old male, were diagnosed with leukaemia and lymphoma respectively at St Vincent’s Hospital in Sydney, Australia, which has been working in partnership with the University of New South Wales’ Kirby Institute. To date, there have been several reported cases of patients cleared of HIV that were related to bone marrow transplants, but this is something new entirely.

HIV_virusTimothy Ray Brown, a US citizen, was treated in 2007/8 for leukaemia with transplanted stem cells from a donor with the CCR5 delta32 mutation – which is resistant to HIV – and was reported clear of the virus. Afterward, Brown stopped taking his antiretroviral medication and remained HIV-free. In 2012, two other US patients were treated with marrow that did not contain the mutation and initially tested clear. But when they ceased taking antiretroviral medication, the virus returned.

The Australian lymphoma patient, treated in 2010, did receive one transplant of bone marrow that contained one of two copies of a gene that is possibly resistant to HIV. However, the leukaemia patient, treated in 2011, received donor marrow with no resistive gene. Both patients remain on antiretroviral medication as a precaution, since the virus may be in remission rather than completely cured.

021204-N-0696M-180The next step is to figure out why the body responds to a bone marrow transplant in a way that makes the virus retreat. One possible explanation is that the body’s immune response to the foreign cells of the transplant causes it to fight harder against HIV. This is because, while bone marrow transplant seems to be the most effective means of clearing the AIDS virus to date, it is not an acceptable risk for patients whose lives aren’t already endangered by bone cancer.

As Professor David Cooper, the study’s senior author and the director of the UNSW Kirby Institute, explained:

We’re so pleased that both patients are doing reasonably well years after the treatment for their cancers and remain free of both the original cancer and the HIV virus… The procedure itself has an up to 10 percent mortality rate. But you take that risk in someone with leukemia or lymphoma because they’re going to die without it, and the transplantation will result in cure. For someone with HIV, you would certainly not transplant them when they have an almost normal life span with standard antiretroviral therapy.

We still don’t know why these patients have undetectable viral loads. One theory is that the induction therapy helps to destroy the cells in which the virus is hiding and that any remaining infected cells are destroyed by the patient’s new immune system.. We need more research to establish why and how bone marrow transplantation clears the virus. We also want to explore the predictors of sustained viral clearance and how this might be able to be exploited without the need for bone marrow transplantation.

The team will be presenting their research 19 July 2014 at the 20th International AIDS Conference in Melbourne, Australia. There, they will be amongst such high-profile speakers as former President Bill Clinton, UNAIDS Executive Director Michel Sidibé and artist and activist Sir Bob Geldof, as well as thousands of the world’s top AIDS researchers, community leaders, people living with HIV and policy-makers at AIDS 2014.

Source: cnet.com, aids2014.com