But, despite the highly active anti-retroviral therapy (HAART) treatment, elements of the virus can still evade the drug. The virus has an in-built survival mechanism, allowing it to create reservoirs of latent, inactive virus that are invisible to the body's immune system and drugs used to treat the disease.
Now, researchers at University of California, Davis, have identified a compound that activates latent HIV, offering the tantilising prospect that the disease can be 'flushed out' of the silent reservoirs where it lurks. If successful, scientists believe their discovery could take them one step closer to a cure for the disease.
Lead author of the study, Dr Satya Dandekar, said: 'We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is already approved and is being used in patients. This molecule has great potential to advance into translational and clinical studies.'
HAART has been relatively successful, reducing HIV infection in newborns, restoring patients' immune systems and lowering viral loads to virtually undetectable levels. But these drugs cannot cure the disease alone. Once treatment is stopped, when a patient's viral load reduces, pools of latent virus reactivate, and the infection comes roaring back. As a result, patients must remain on treatment indefinitely, increasing their risk of long-term toxicity.
Dr Dandekar said: 'We've made great progress, but at the end of the day you still have more than 30 million people walking around with HIV. Without drugs, the virus can come back at the same threat level for patients. Eradicating HIV is extremely critical.'
Elimination of the virus can only be achieved if these latent pools are reactivated and destroyed - a strategy called 'shock and kill'. Researchers across the world have been working on this approach, but finding the right compounds has proved challenging. A successful molecule must be able to target the proteins associated with HIV latency, without overstimulating the immune system for fear of triggering severe side effects.
But the UC Davis team believe their compound PEP005 - the active ingredient in a Food and Drugs Administration already approved anti-cancer drug PICATO - increases HIV activation in patient's blood samples. And, they noted, the molecule showed low toxicity.
However, HIV is a complicated virus and, as clinicians have discovered with HAART, it must be treated through multiple means. In addition to PEP005, the researchers tested other compounds capable of reactivating HIV through different pathways.
This painstaking process identified another molecule, JQ1, which works with PEP005 to maximise HIV activation. PEP005 when combined with JQ1 increased HIV activation up to 15-fold.
While these results are promising, researchers are mindful that 'shock' only works when it's followed by 'kill.'
'First, we need to identify the best combination of latency-activating agents. Then we must help patients clear these reactivated cells. Just reactivating the HIV from latency won't be enough.' said Dr Dandekar.
Dr Dandekar notes that many HIV patients receiving HAART regimens have robust immune responses, which will go a long way towards clearing the virus. She also believes HIV vaccines in development could give patients an extra edge.
Even a vaccine that isn't 100 per cent effective at preventing transmission could boost a patient's ability to destroy reactivated virus, she said.
However, identifying PEP005 and JQ1 as potent HIV-activators is a key step in the right direction.
'It is really exciting is that the molecule in PICATO is already approved and being used by patients. In addition to being very effective in reactivating HIV, it also works beautifully with other latency reactivating agents, is less cytotoxic and doesn't cause a major immune response.'
The study was published in the journal PLOS Pathogens.
Source: MailOnline
Now, researchers at University of California, Davis, have identified a compound that activates latent HIV, offering the tantilising prospect that the disease can be 'flushed out' of the silent reservoirs where it lurks. If successful, scientists believe their discovery could take them one step closer to a cure for the disease.
Lead author of the study, Dr Satya Dandekar, said: 'We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is already approved and is being used in patients. This molecule has great potential to advance into translational and clinical studies.'
HAART has been relatively successful, reducing HIV infection in newborns, restoring patients' immune systems and lowering viral loads to virtually undetectable levels. But these drugs cannot cure the disease alone. Once treatment is stopped, when a patient's viral load reduces, pools of latent virus reactivate, and the infection comes roaring back. As a result, patients must remain on treatment indefinitely, increasing their risk of long-term toxicity.
Dr Dandekar said: 'We've made great progress, but at the end of the day you still have more than 30 million people walking around with HIV. Without drugs, the virus can come back at the same threat level for patients. Eradicating HIV is extremely critical.'
Elimination of the virus can only be achieved if these latent pools are reactivated and destroyed - a strategy called 'shock and kill'. Researchers across the world have been working on this approach, but finding the right compounds has proved challenging. A successful molecule must be able to target the proteins associated with HIV latency, without overstimulating the immune system for fear of triggering severe side effects.
But the UC Davis team believe their compound PEP005 - the active ingredient in a Food and Drugs Administration already approved anti-cancer drug PICATO - increases HIV activation in patient's blood samples. And, they noted, the molecule showed low toxicity.
However, HIV is a complicated virus and, as clinicians have discovered with HAART, it must be treated through multiple means. In addition to PEP005, the researchers tested other compounds capable of reactivating HIV through different pathways.
This painstaking process identified another molecule, JQ1, which works with PEP005 to maximise HIV activation. PEP005 when combined with JQ1 increased HIV activation up to 15-fold.
While these results are promising, researchers are mindful that 'shock' only works when it's followed by 'kill.'
'First, we need to identify the best combination of latency-activating agents. Then we must help patients clear these reactivated cells. Just reactivating the HIV from latency won't be enough.' said Dr Dandekar.
Dr Dandekar notes that many HIV patients receiving HAART regimens have robust immune responses, which will go a long way towards clearing the virus. She also believes HIV vaccines in development could give patients an extra edge.
Even a vaccine that isn't 100 per cent effective at preventing transmission could boost a patient's ability to destroy reactivated virus, she said.
However, identifying PEP005 and JQ1 as potent HIV-activators is a key step in the right direction.
'It is really exciting is that the molecule in PICATO is already approved and being used by patients. In addition to being very effective in reactivating HIV, it also works beautifully with other latency reactivating agents, is less cytotoxic and doesn't cause a major immune response.'
The study was published in the journal PLOS Pathogens.
Source: MailOnline
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