Today’s drugs have turned HIV from a quick death sentence into a chronic disease, albeit a terminal one. There are a number of problems with HIV therapies. The main one being that they don’t eliminate HIV because they can’t reach the two known pools of cells where the virus can hide and lie dormant. This means that eventually the drugs stop working as the body becomes resistant to them, requiring a change in combination therapies to combat the disease.
One pool is formed by so-called memory T cells. These are the cells that carry an imprint so if you get, for example, measles or mumps as a child, you will be forever immune. They live for years, even decades, making them a logical HIV hideout. Scientists have repeatedly sought to manipulate them, with little success.
The second pool is formed by macrophages, another type of blood cell involved in the immune system. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they usually commit suicide and die. Instead, HIV instead keeps them alive long past their normal lifespan, harbouring the genetic material and ensuring that the infection remains in the body. In theory, getting rid of the macrophage reservoirs would also clear some of the hidden HIV. Think of it like Star Trek where the Klingons switch their energy force on, hiding them from the Starship Enterprise. You can’t hit what you can’t see!
Like cancer, we can see that the HIV virus is very clever at ensuring it’s survival. Even more interesting, recent research has shown that some pathways that are being studied in cancer may also be crucial in the fight against HIV also. Scientists at the University of Rochester were trying to figure out how to kill the macrophages hiding the HIV virus. Eventually, the research team realised that HIV produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt, which in turn prevents cell suicide or apoptosis.
To test this hypothesis, in the latest issue of Retrovirology, they put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any of them killed the cells. Miltefosine and a related drug, perifosine, both rapidly killed the macrophages.
Perifosine is being studied as a potential cancer drug in clinical development. Miltefosine is an old drug known to be safe in leishmaniasis, as an anti-parasitic therapy. The researcher’s next goal is to study the already available miltefosine in animals, to see if it targets and kills infected macrophages well enough for them to then test in HIV patients.
If the concept of targeting Akt in the macrophages works, it would mean a major breakthrough in HIV/AIDS treatment because killing the infected macrophages would deprive the HIV of one of its hideouts, potentially improving the efficacy of current therapies and hopefully leading to improved long term survival for HIV patients.
As a logical extension, killing both pools where HIV hides dormant in the body may one day lead to a ‘cure’ and eradication of the HIV infection. But that a pipe dream in the future; at least today new research is offering hope that this may one day be possible.
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