"Identification of drug combinations that reverse HIV-1 latency"

[tryingtostay]

Link

There are almost 40 million people throughout the world living with HIV-1/AIDs. While current antiretroviral therapies are able to reduce the amount of virus in the blood, HIV remains present in a latent state within T cells. Reactivation of latent HIV-1 in combination with potent antiviral drugs has potential as a strategy to eradicate the virus from infected individuals.

A new study in the Journal of Clinical Investigation reports on the development of a multifaceted approach for identifying drug combinations that reverse HIV-1 latency. Robert Siliciano and colleagues collected T cells from HIV-infected individuals and assayed these cells for the presence of HIV-1 within cells and the production and section of intact virus, which is indicative of reactivation.

A comparison of various 2-drug combinations revealed that several were able to reverse latency. Importantly, several combinations were able to reactivate HIV-1 without the development of an inflammatory response.

The authors also developed a model to correlate changes in HIV-1 RNA in a patient's blood with the amount of virus secreted from isolated T cells. The techniques developed in this study have potential to inform future clinical trials for strategies to eliminate HIV-1 reservoirs in infected individuals.

[buginme2]

At my last appointment at the AIDS clinic they took some blood to be included in a clinical trial to further this study.  They were going to look at my aids infected cells to see if they could reverse the latency.


Best part was they paid me $10 for my tainted blood which covered the cost of parking.  Cha Ching.

Your welcome

[Wade]

Was there a name for the test , or just under clinical trials ?

[buginme2]

Was there a name for the test , or just under clinical trials ?

Is your question directed to me? I'm not sure the answer to it. 

The clinic I go to has a "aids clinical trial unit" attached to it since I go to a medical university for my healthcare that does research too.  On a few of my routine appointments they ask if they can take some blood for research. 

The last time the took it was because they are developing a new viral load test that they can use in places like Africa that don't have access to a lab.  Another time it was to see if they could use drugs to flush out the latent virus. 

I've always jumped at the chance because A. It's $10 and parking is really expensive here so that helps and B. It's  ice to be able to help even if it is just helping a little. 

[geobee]

Ten bucks?  Heck, at the trials I participate in they give me $20!  (In fact, going tomorrow).  I try to participate as much as possible at San Francisco General's Options Program and at Quest Clinical Research in SF.  Both have drawn a lot of blood over the years.  Also, it keeps me in contact with some of the "rock stars" in the field and some of the latest research.

[DANIELtakashi]

Thank you for the info.
Does anybody know what combination has potential?
Hope this will work.   I am anxiously waiting for a cure although people say it will be difficult.

[tryingtostay]

What is the pipeline for something in the Journal of Clinical Investigation to get into trials?  Or is that some sort of guide to help doctors prescribe meds when a cure comes along?

[buginme2]

Ten bucks?  Heck, at the trials I participate in they give me $20!  (In fact, going tomorrow).  I try to participate as much as possible at San Francisco General's Options Program and at Quest Clinical Research in SF.  Both have drawn a lot of blood over the years.  Also, it keeps me in contact with some of the "rock stars" in the field and some of the latest research.

Seattle is always playing second to SF (except when it comes to football or quality of life of course). 

I wonder if it's negotiable.  I'm going to counter offer next time, open up the negotiations. 

What is the pipeline for something in the Journal of Clinical Investigation to get into trials?  Or is that some sort of guide to help doctors prescribe meds when a cure comes along?

What?  Don't get your question.


If your expecting a cure in the next twenty years your going to be disappointed

[tryingtostay]

What?  Don't get your question.

I don't understand how something could go from the 'Journal of Clinical Investigation' into clinical trials and I was just curious if Clinical trials would be the next step.  Or am I wondering how I can taste the flavor of an orange from an apple?

[elf]

I took Antabuse for 3 months (that was two years ago) and saw no change in my numbers.

Disulfiram is the subject of research for treatment of cancer and HIV (to activate the reservoir of HIV-infected resting CD4 cells

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

A more recent study indicates why it didn't work:

the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data.

http://www.ncbi.nlm.nih.gov/pubmed/24875931


WARNING:

HDAC inhibitors, particularly vorinostat, are currently being investigated clinically as part of a "shock-and-kill" strategy to purge latent reservoirs of HIV. We demonstrate here that vorinostat increases the susceptibility of uninfected CD4(+) T cells to infection with HIV, raising clinical concerns that vorinostat may reseed the viral reservoirs it is meant to purge, particularly under conditions of suboptimal drug exposure. We demonstrate that vorinostat acts following viral fusion and enhances the kinetics and efficiency of reverse transcription, nuclear import, and integration. The effect of vorinostat was recapitulated using the cytoplasmic histone deacetylase 6 (HDAC6) inhibitor tubacin, revealing a novel and previously unknown cytoplasmic mechanism of HDAC inhibitors on HIV replication that is distinct from their well-characterized effects of long-terminal-repeat (LTR)-driven gene expression. Moreover, our results suggest that treatment of patients with class I-specific HDAC inhibitors could induce latent viruses without increasing the susceptibility of uninfected cells to HIV.

http://www.ncbi.nlm.nih.gov/pubmed/25008921

[geobee]

Here's a recent story on new funding for vorinostat --

http://www.newsobserver.com/news/business/article17098307.html

"The UNC clinical trial will combine Argos’s AGS-004 with a second therapy to make HIV-infected cells more visible to the immune system to maximize the immune system’s attack. UNC will contribute the agent, vorinostat, to lure the HIV out of hiding, and Argos will supply the weapon to destroy it.

UNC published the first research on exposing hidden HIV a decade ago, and the procedure “didn’t work so well,” Margolis said. Subsequent research, published in 2012 in the journal Nature, perfected the technique, he said."

PS:  San Francisco *is* a little pricey and our football team is struggling (why did we trade Alex Smith?) -- but the weather is great! 

[elf]

PS:  San Francisco *is* a little pricey and our football team is struggling (why did we trade Alex Smith?) -- but the weather is great!

Compared to Livermore it's not that great (too windy in the summer).