Waking up dormant cells

[John2038]

Sources
theaustralian.com.au
radioaustralia.net.au
..
By using cancer drug, Vorinostat, for two weeks, Prof Lewin had been able to turn on sleeping HIV-infected cells so they could be detected

[Dr.Strangelove]

Lewin also gave a talk at CROI

It's good to see a step in the right direction to tackle the dormant cells. But it seems that HIV lies dormant in different types of cells, not all of them can be awaken by Vorinostat. So, this is only a piece of the puzzle. Like always.

[geobee]

Not to mention it's carcinogenic. 

A lot of work is being done to wake up latent cells.  Google "Bryologs" for example (and there's a thread here about that somewhere).  Smart people (Drs. Siliciano, Margolis, Deeks, etc. )  I'm confident they'll find something that works and hopefully isn't too toxic.

[elf]

Latent reservoirs cleaning ''substances'' need to be tested, and it can take 10 years or more.

So, why not use meds that are considered safe, and are already widely used in clinical settings, like

1) Disulfiram /Antabuse
http://en.wikipedia.org/wiki/Disulfiram



   

RESULTS:

    DSF reactivated latent HIV-1 expression in the U1 cell line, but not in the J89GFP or ACH2 cell lines. Interestingly, we found that DSF significantly reduced phosphatase and tensin homolog (PTEN) protein levels in U1 cells and in resting CD4 T cells from HIV-negative donors. Decreased PTEN resulted in increased phosphorylation of protein kinase B (Akt) and activation of the Akt signaling pathway. Consistent with these finding, pharmacological inhibitors of Akt and nuclear factor-kappaB (NF-κB) block the latent HIV-1-reactivating activity of DSF. Furthermore, we show that HIV-1 expression in the U1 cell line could be activated by a small molecule inhibitor of PTEN or by siRNA knockdown of PTEN expression. Neither the J89GFP nor ACH2 cells express PTEN, explaining the lack of DSF effect on HIV-1 expression in both these cell lines.
    CONCLUSION: DSF reactivates latent HIV-1 expression via the Akt signaling pathway through depletion of PTEN.

http://www.ncbi.nlm.nih.gov/pubmed/22739395


2) Miltefosine / Impavido
http://en.wikipedia.org/wiki/Miltefosine

    Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary human macrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells.

[geobee]

Dr. Deeks at UCSF is testing disulfiram / antabuse.

[Ann]

1) Disulfiram /Antabuse
http://en.wikipedia.org/wiki/Disulfiram

Elf, have you, or has anyone you know, ever taken Antabuse? It's pretty nasty stuff. For many people, even ingesting small (tiny) amounts of alcohol (such as found in cough syrups, OTC cold remedies, as well as quite a few foods) can set off the adverse reaction and make a person tied to puking into their toilet for the next several hours. Not to mention the headache etc.

You'd have to be pretty dedicated to reading every single label of anything you ingest while taking it. It may be considered "safe" but every single person I know who has taken it wouldn't wish it on their worst enemy. (Well, ok, one or two would wish that, but not most.)

Ick. I think I'd rather have to keep my hiv than to take that stuff for the length of time that would likely be required in order to do what they only think it might do. Antabuse has fallen out of favour in alcohol rehab circles (with good reason) and it sounds like "someone" is just trying to find a new use for it. Kinda like they did with AZT.

[Jeff G]

Antabuse was prescribed in the 80's because it would raise your cd4 counts ... so some docs prescribed it off label for this purpose . I didn't last two weeks on it before I ingested some alcohol in cough syrup that I wasn't aware of ... it was awful .