http://www.sciencecodex.com/george_mason_rese...w_factor_in_hiv_infection

A George Mason University researcher team has revealed the specific process by which the HIV virus infects healthy T cells—a process previously unknown. [...] Researchers and doctors have known for some time that the HIV virus, rather than directly killing healthy T cells, actually hijacks them. This eventually leads to their destruction. So the virus essentially turns the infected T cells (also known as CD4T cells or helper T cells) into a factory for creating even more HIV. Learning more about how the cells are infected could be a key step toward figuring out how to stop infection altogether. Wu's latest discovery builds upon his previous work, published in the journal Cell in 2008, which described the basic process of how HIV infects T cells. After discovering that cofilin—a protein used to cut through a cell's outer layer, or cytoskeleton—is involved in HIV infection, Wu's new research provides the detailed framework for this process. This new factor is called LIM domain kinase, or LIMK. The researchers discovered that LIMK triggers a cell to move, almost acting like a propeller. This cell movement is essential for HIV infection. This discovery marks the first time that a research team has uncovered the involvement of LIMK in HIV infection. Building upon these results, the researchers then used a drug to trigger similar LIMK activation and found that it increased infection of T cells. Of course, the researchers ultimately want to decrease the infection of T cells—so they worked backwards and found something very promising. "When we engineered the cell to inhibit LIMK activity, the cell became relatively resistant to HIV infection," says Wu. In other words, the researchers engineered human T cells that were not easily infected by HIV. This finding suggests that, in the future, drugs could be developed based on LIMK inhibition. And while there are currently no medical drugs available to inhibit LIMK, Wu hopes this is a developing area in potential new therapeutic targets. [...]

HDAC inhibitors Inactive in Primary CD4 T Cells?

The results reported in the paper of Sahu GK et al are quite embarassing. Several experiments performed in the last few years have demonstrated the role of chromatin modeling in the maintenance of HIV latency and gave hope for new strategies able to "purge" the HIV reservoir...
...The Use of Histone Deacetylase Inhibitors (HDACi) for Purging HIV Reservoirs Could Be Compromized by Their Lack of Activity in Primary CD4 T Cells Compared to Cell Line Models of HIV Latency.
...However, at least two clinical trials have started with SAHA: one headed by Sharon Lewin, Monash University, Melbourne, Australia and another by David Margolis, University of North Carolina in Chapel Hill, USA. These two trials will undoubtfully bring important and very informative data for future purging clinical trials.

http://www.hiv-reservoir.net/latest-news-on-h...-primary-cd4-t-cells.html

Gold-based Drug May Pave the Way to a Cure for AIDS

"Using a compound containing gold and approved for treatment of rheumatoid arthritis, researchers have been able to hit the hidden stock of HIV which cannot be targeted by current antiretroviral therapies".

"We serendipitously found that one drug that we were evaluating as a candidate for the shock and kill caused the death of the central memory T-cells, leaving their precursors (i.e. the naïve cells) partially intact".

http://www.hiv-reservoir.net/index.php/the-ne...o-hit-hiv-reservoirs.html


Trojan Horse Against HIV

"The idea is quite interesting: encapsulate factors able to reactivate HIV from latency in nanoparticles capable to enhance delivery in tissues, brain, or even specific cells. In particular, liposomes offer a biodegradable vehicle which is capable of carrying a variety of substances to target sites either through passive or active targeting... This original experiment therefore leads to the construction of a kind of Trojan Horse against HIV, able to target specifically different kind of cells, and both deliver anti-latency agents and antiretrovirals. A genious weapon in the battle against HIV persistence!"

http://www.hiv-reservoir.net/index.php/the-ne...an-horse-against-hiv.html

Suggest that this is an extremely serious issue. In many ways TB is probably more dangerous to the HIV positive than HIV itself. TB is probably the biggest global killer of the HIV positive, and the spread of multi-drug resistant TB could wipe out the benefits of decades of advance in AIDS research. What would be the point of taking potent anti-HIV therapy if TB was going to eventually kill a person anyway and in a lot less time than HIV itself? Suggest the World Community Grid should give priority to getting involved in the search for new drugs to help fight drug resistant TB. This would benefit all people and especially the HIV positive.

http://www.medicalnewstoday.com/articles/234376.php

Article Date: 14 Sep 2011

Resistant TB Spreading In Europe At Alarming Rate, WHO

Forms of tuberculosis (TB) that resist drugs are spreading in Europe at alarming rates, says the World Health Organization (WHO). A new report from the organization says Multidrug-Resistant Tuberculosis is a disease that could cause a pandemic in Western Europe.....TB is an old disease that never went away, and now it is evolving with a vengeance..."

http://nymag.com/print/?/health/features/aids-cure-2011-6/

The Man Who Had HIV and Now Does Not

Four years ago, Timothy Brown underwent an innovative procedure. Since then, test after test has found absolutely no trace of the virus in his body. The bigger miracle, though, is how his case has experts again believing they just might find a cure for AIDS. [...] people with a certain natural genetic mutation are very resistant to the virus. The mutation, called delta 32, disables CCR5, a receptor on the surface of immune-system cells that, in the vast majority of cases, is HIV’s path inside. People with copies from both parents are almost completely protected from getting HIV, and they are relatively common in northern Europe - among Germans, the rate is about one in a hundred. Hütter resolved to see if he could use a stem-cell donor with the delta-32 mutation to cure not just Brown’s leukemia but also his HIV. [...] More than four years after he stopped taking anti-retroviral therapy, there is also no sign of HIV in his body. Brown is now surely one of the most biopsied humans on Earth. Samples from his blood, his brain, his liver, his rectum, have been tested over and over. People in whom the disease is controlled with anti-retroviral therapy will still have hidden HIV -perhaps a million copies. But with Brown, even the most sensitive tests detect no virus at all. Even if trace amounts remain (it is impossible to test every cell), it no longer matters. Absent the CCR5 receptors, any HIV still present cannot take root. He is cured. [...] a clinical trial in San Francisco and Philadelphia is testing whether using the genetic scissors not on stem cells but on T-cells [...] to modify them with the CCR5 mutation can also yield HIV resistance. [...] While the pharmaceutical industry has sunk hundreds of millions of dollars into developing AIDS treatments, most drug companies are sitting out cure research. (One big exception is Merck, which is funding studies of some of its drugs’ possible uses in eradication; Gilead is also looking at its compounds for cure candidates.) It’s no mystery why. "The whole field suffers from the lack of a business model," says Jeff Sheehy, a San Francisco activist and CIRM board member. "A cure may make sense from a public-policy point of view, but not to a company." Unlike treatment, which must be taken daily for life, a cure would be a one-time intervention. "It’s not that it’s sinister and they don’t want a cure. But it doesn’t fit." Drugmakers’ indifference can doom promising potential cures, as compounds owned by a company can’t be used by anyone else. Many AIDS researchers are particularly excited about the eradication possibilities of a substance developed by Medarex. But Medarex was bought in 2009 by Bristol-Myers Squibb, which is testing the compound on cancer but doing nothing visible with it on HIV. (A spokeswoman says the company is "considering the use" of the drug in HIV research, but no trials are set.) Nor has the NIH’s National Institute of Allergy and Infectious Diseases, the world’s largest funder of AIDS research, made a priority of cure research. According to its own figures [...] the NIAID spent $40 million on cure research in 2009. That’s 3 percent of its total AIDS-research budget. (Fauci argues that this doesn’t take into account other research that may eventually apply to a cure.) Until recently, the NIAID did not even have an internal code for AIDS-cure work. [...]