A cure for HIV/AIDS has been elusive.?But a class of drugs called HDAC inhibitors, used to treat lymphoma, have provided renewed hope.
The interplay between cancer treatments and HIV has been interesting to watch. ?We?d posted earlier about?bone marrow transplants, given to lymphoma patients, possibly curing the patients? HIV. ?We?d also noted that?HIV itself is now being researched as a possible treatment for leukemia.
Now scientists are looking at another lymphoma treatment, HDAC inhibitors, as a possible vehicle for curing HIV.
In order to understand why HDAC inhibitors may have promise in curing HIV, you need to first understand why it?s been so difficult to find a cure for HIV in the first place. ?Here?s why:
1. The HIV virus mutates fairly easily. These mutations may make the virus resistant to some antiretroviral (ARV) drugs, causing an increase in viral load (the amount of virus measured in the body).
2. A second difficulty is the awesome amount of raw virus that can be produced each day in a patient infected with HIV. Up to 10 billion new virus particles can be produced in a 24 hour period.
3. A third reason impediment to finding a cure is that some virus can enter cells and remain dormant, sometimes for a very long time.
The HIV virus enters cells, transcribes its RNA into DNA, merges with the cell?s native DNA and waits. The virus?has safely sequestered itself from the patient?s immune system and the ARV medications the patient is taking. It remains there, ready to become active at some future time. HIV can remain there, inactive and hidden, for a long time. ?It is estimated that, based on the number of infected cells, the amount of virus present, nature of the ARVs used and other factors a patient would need to stay on ARVs for 70 years before all of the dormant virus activated and was subsequently destroyed.
While the patient remains on antiretroviral therapy the viral load may become undetectable. At times, in some cells, the viral DNA may become active again, even while on ARVs. The renewed activity will cause production of new virus that will be released into the circulation, and cause the death of the cell producing the virus. Once the HIV is free, however, the ARVs can work against it and neutralize it. But take the patient off of antiretroviral medications and, sooner or later, some viral DNA will activate and spread. And with no ARVs being present, more cells become infected and the viral load rises. Thus ARVs are thus not a cure for HIV, by themselves, because they don?t get at all the hidden virus.
Research has shown that histone deacetylase (HDAC) inhibitors can disrupt the ability of the hidden virus to lie dormant. It worked when tested in the lab, at least. But when an HDAC inhibitor, valproic acid, was given to HIV-positive patients, it had little effect. Fortunately, HDAC inhibitors can be useful to treat some types of lymphoma (a cancer comprised of lymphocytes, like T cells).
A doctor using one HDAC inhibitor, vorinostat ? which is a different HDAC inhibitor than valproic acid ? on?lymphoma patients wondered if it would also work clinically in HIV patients to activate the hidden virus, which then would permit the ARVs to do their work.
He gave just a few doses of vorinostat to a small group of eight HIV-positive patients who were on ARVs. What the research group found was that, shortly after the administration of the vorinostat, there was an increase in HIV markers. Later the HIV markers declined dramatically. They interpreted this as the drug causing the sequestered (hidden) HIV DNA to activate and produce virus. That virus was then neutralized by the antiretroviral drugs the patients were still taking, and cleared from the body.
The researchers propose that, by giving vorinostat for longer periods, perhaps all of the hidden HIV might be activated, flushed from the cells, and neutralized by the ARVs.
Additional research is underway to determine optimal dosing of the drug. Proposed research may include testing other HDAC inhibitors to see if different ones might be even more effective than vorinostat. The hope is that in the near future, perhaps a combination of ARVs, plus an HDAC inhibitor, might lead to a real cure for HIV.
Source: http://americablog.com/2013/07/cure-hiv-aids-hdac-inhibitors-cancer.html
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