Therapy developed at UNC targets HIV hidden in cells

03/16/2014 12:00 AM

03/12/2014 5:43 PM

HIV – the virus responsible for AIDS – is difficult if not impossible to kill. A major reason? It knows how to hide.

Conventional medicines can attack HIV, but remnants often remain hidden in patients’ cells, ready to re-emerge and further drive the progression of AIDS.

In a paper published in the January edition of PLOS Pathogens, J. Victor Garcia-Martinez and colleagues from the UNC School of Medicine demonstrate a new and effective way to attack the hidden HIV. Eventually, their method could one day be used in conjunction with treatments already available to better treat AIDS.

Currently, treatments consisting of up to three drugs are used to prevent the growth of HIV in patients suffering from AIDS. However, these treatments don’t eliminate the HIV virus, but only reduce its ability to reproduce.

“Antiretroviral therapies do not kill either virus or infected cells. They only affect the ability of the virus to grow,” Garcia-Martinez said.

Instead of relying on traditional therapies, Garcia-Martinez and his colleagues have taken a different approach: They devised a way for the body to detect cells with hidden HIV, so the immune system can identify and kill the cells.

“The immunotherapy that we used does kill the cells that are infected by HIV,” Garcia-Martinez said. “This is a key difference.”

In the paper, Garcia-Martinez and his team studied what are known as “BLT mice,” which have human immune systems. Using these mice allows researchers to better understand how new treatments might affect human cells and tissues.

“The BLT mouse is the most advanced model of its kind, and whereas other ‘humanized’ mice have been used for HIV studies, no other model has been used for this purpose,” Garcia-Martinez said.

The researchers tested what they call the “kick and kill” strategy to attack HIV in the mice. They used a compound that “kicks” the virus into an “on” state in cells where it is hidden in an “off” state. Once the hidden virus is turned on, the immune system can identify it, and then kill the cells where it is hiding.

“This is a very important concept,” Garcia-Martinez said.

“In patients, there are cells infected with HIV that do not express any virus. These are usually resting cells. In these cells, the virus lies dormant. Therefore, the infected cells themselves (and the virus they contain) remain invisible to the immune system.”

In the paper, Garcia-Martinez and his team show this method can reduce the amount of hidden HIV by up to six times normal levels. Eventually, said Garcia-Martinez, they hope to develop treatments that can destroy hidden HIV virus, and dramatically reduce patients’ future risk of AIDs.

“The goal for interventions like the immunotoxin used in our manuscript is to eventually eradicate the virus in infected cells from the body. How long it would take to accomplish this is yet to be determined,” Garcia-Martinez said.

“Our experiments were not designed to demonstrate eradication but rather efficient killing of HIV infected cells in human tissues. This effect was beyond what antiretroviral therapy is able to do on its own. Future experiments planned will address the issue of how long and under what circumstances can we completely eradicate the virus from the body.”

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