POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: Mishma on July 16, 2013, 10:25:04 am
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http://hiv-reservoir.net/index.php/the-news/430-drug-free-remission-of-aids-in-monkeys.html "This is the most exciting finding in my entire life," said Dr. Andrea Savorino.
I haven't been following this line of research, nor have I read the article in Retrovirology, from which the study comes from. Nonetheless, I desperately needed some "good" news and this came to my in-box this AM. My guess as to the mechanisms involved here, is that the two additional agents added to the ART regimen, reawakened infected memory cells which in turn were destroyed by either host factors or interactions with HAART. If anyone has access to the original article I would love to see it.
"However, another important step in this direction, that is the development of a scalable strategy able to induce a drug-free remission of AIDS in monkeys, is finally in the pipeline, researchers report in Retrovirology, one lead scientific journal in the field.
Apart from rare cases of drug-free remission obtained treating very early with regular antiretroviral therapies, a cure for AIDS has been so far obtained only in Mr. Timothy Brown, i.e. the "Berlin patient", and, possibly, in two other recently reported cases in Boston. In all these patients, who also suffered from hematological malignancies, invasive and life-threatening techniques have been applied to remove the blood cells (including those harboring the virus) and replace them with new virus-free and cancer-free cells. Therefore, novel strategies are needed that be both safe and scalable to the 33 million people living with HIV/AIDS worldwide.
Now, by adding to antiretroviral therapy two existing drugs, i.e. the gold salt auranofin and the chemosensitizing agent buthionine sulfoximine (BSO), an Italian and American research team, led by Dr. Andrea Savarino at the Italian NIH (www.iss.it), observed, after therapy suspension, a drug-free remission of the disease in the macaque AIDS model (i.e. the animal model most closely resembling human AIDS).
The drug combination safely and gradually replaced the "diseased" white blood cells with fresh and efficient cells, although, at first, it did not prevent the initial viral rebound after therapy suspension. "However", says Dr. Andrea Savarino, "during the subsequent follow up of the macaques, the new immune cells fought back the virus, rescuing the macaques to healthy conditions reminiscent of a drug-free remission of AIDS". "It's been the most exciting finding in my entire life", he concludes. “It turns out that a specific branch of the immune system is boosted by the addition of BSO to the drug cocktail, possibly mimicking an auto-vaccination against the virus”, adds Iart Luca Shytaj, a collaborator of Dr. Savarino and first author of the article published in Retrovirology."
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Very interesting. Dr. Savarino is one of the pioneers of reservoir clearance strategies and I believe this study is in collaboration with Duke University. Any idea how well macaque studies translate into results in humans?
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Unfortunately, Chimps remain the best model but they are now an endangered species.
I pulled an current abstract which highlights elements of the innate immune response (our first line of defense which includes physical barriers, pattern and damage recognition receptors) which are problematic in using this as a model system. I would refer you to the numerous abstracts, links and reviews I posted in the Research Forum under the title Innate Immune Responses for further background info). Too much to regurgitate here. Regardless, I've been asserting for years that within this system lies our salvation.
http://www.frontiersin.org/Virology/10.3389/fmicb.2013.00176/abstract
Macaques as model hosts for studies of HIV-1 infection
Anisha Misra, Rajesh Thippeshappa and Jason T. Kimata*
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
Increasing evidence indicates that the host range of primate lentiviruses is in part determined by their ability to counteract innate restriction factors that are effectors of the type 1 interferon (IFN-1) response. For human immunodeficiency virus type 1 (HIV-1), in vitro experiments have shown that its tropism may be narrow and limited to humans and chimpanzees because its replication in other non-human primate species is hindered by factors such as TRIM5α (tripartite motif 5 alpha), APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3), and tetherin. Based on these data, it has been hypothesized that primate lentiviruses will infect and replicate in a new species if they are able to counteract and evade suppression by the IFN-1 response. Several studies have tested whether engineering HIV-1 recombinants with minimal amounts of simian immunodeficiency virus sequences would enable replication in CD4+ T cells of non-natural hosts such as Asian macaques and proposed that infection of these macaque species could be used to study transmission and pathogenesis. Indeed, infection of macaques with these viruses revealed that Vif-mediated counteraction of APOBEC3G function is central to cross-species tropism but that other IFN-induced factors may also play important roles in controlling replication. Further studies of these macaque models of infection with HIV-1 derivatives could provide valuable insights into the interaction of lentiviruses and the innate immune response and how lentiviruses adapt and cause disease.
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It's the continuation of this study:
http://forums.poz.com/index.php?topic=43938.0
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With the notable exception of adding the chemosensitizing agent buthione sulfoximine (interferes with glutathione processes) to HAART in addition to Auranofin.
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Here's a little more info on the study -- found this surfing the web this AM --
http://www.chessbase.com/Home/TabId/211/PostId/4010544/a-long-term-cure-for-hiv-in-the-offing-260713.aspx
His conclusions are notable --
"Our most important result so far has been the achievement of a functional cure (see point 1) in macaques. We achieved this result by using a combination of antiretroviral therapy (the standard baseline therapy for HIV infected patients) and two experimental drugs: auranofin and buthionine sulfoximine.
Our drug combination is administered only once and only for three months. After these three months the therapy is stopped and the macaques are able to control the virus independently without showing signs of disease progression.
The main advantage of our therapy over the current situation is that it spans for three months instead of the whole life of the patient. This may allow to provide a globally scalable curing strategy."
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Thanks for the link. I know the ramifications are potentially huge but after close to 30 years + I've all but given up hope for myself-given my age and number of co-morbidity's. But hope dies last.
I'm anxiously awaiting the clinical trials, which according to what I've read might begin next year, especially since these drugs have been around for some time. All the more reason to pay attention at the next CROI meeting where I believe the announcement will be made.
For me, and I'm sure others, HIV has already seeded our brains; will this functional cure also handle HAND and other CNS/PNS disorders. The HIV in my system has been under control since shortly after going on HAART (95/96?).
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Mishma: perhaps Stem Cell therapies will retore our health to normal conditions post-cure. ;)
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Such news are the best antidepressants. :D
They turn on the light in the end of the tunnel.