In test-tube experiments, Italian researchers have managed to selectively stimulate and then destroy previously dormant HIV-infected immune cells using a combination of two drugs.
The experiment, by Dr Andrea Savarino and colleagues from Italy’s Istituto Superiore di Sanita, is the latest to use an idea that has been dubbed “shock and kill”. In this technique, quiescent HIV-infected cells are first genetically “woken up” by one chemical so that they start to produce HIV and then selectively destroyed by another one. If every infected HIV cell in the body could be enticed out of hiding and destroyed, this would amount to a cure of HIV infection.
HIV infection is lifelong because it can exist inside a reservoir of long-lived immune cells that are not actively dividing or producing virus and are therefore invisible to the immune system. During periods when such cells are active, they can be seen by the immune system, but they also recharge this reservoir.
Savarino and colleagues first used a drug called a class 1 histone deacetylase (HDAC) inhibitor to waken up cells. They then added a drug called buthionine sulphoximine which depleted cells of the vital antioxidant glutathione, making them more likely to self-destruct. The HIV-infected cells in the test tube died out while the non-infected cells stayed intact.
Dr Savarino commented that such molecular weapons “in combination with antiretroviral therapies, could hopefully allow people with HIV/AIDS to get rid of the virus”. However, he warned that cells may use many different ways of lying dormant and this specific technique might only work against certain ones.
Previous experiments using valproic acid, another HDAC inhibitor, found that activity in the test tube did not translate into reservoir depletion in humans.
With Thanks To NAM
