Highly active antiretroviral therapy (HAART) has been a game changer in the battle against HIV, the virus that causes AIDS.
It suppresses the deadly virus to virtually undetectable levels in the blood, so those being treated for HIV can live almost symptom-free for as long as they take the drugs.
However, if a patient stops therapy, there are silent reservoirs of HIV — undetected by the immune system — that spring to life and reignite the virus.
The latest avenue of research involves discovering drugs that flush out this silent reservoir, so the virus can be recognized and killed by the immune system.
One drug that shows particular promise at unmasking the virus, potentially offering a cure, is a compound called PEP005, which is used to treat precancerous skin lesions.
Satya Danekar, chair of medical microbiology and immunology at the University of California-Davis, is leading research into PEP005.
“You flush the virus out from those latently infected cells and pull them out," Danekar said. "And second, you have to depend on the ability of the immune system to now come and say, 'Whoa, there’s the infected cell,' and come and kill it.”
She called the strategy to awaken silent HIV “shock and kill.” Researchers report their findings in the journal PLoS Pathogens.
So far, PEP005 has been shown effective in awakening latent reservoirs of the AIDS virus in cells from infected individuals.
Dandekar said PEP005 would be given to patients at the same time they are on HAART to suppress active virus.
The compound has also been shown to protect other immune cells from becoming infected with HIV.
Dandekar said the success of HAART is that many HIV patients are now growing old, but it’s not known how well seniors are able to tolerate the toxicity and side effects of antiretroviral drugs.
In addition, Dandekar noted that combination therapy is a lifelong commitment, not only for patients but for countries that provide HAART to their citizens. She said that could be a hardship for many countries.
“You have all these people — you have to keep treating them, following, monitoring," she said. "So, again, human life and treatment is important. But there is this other side effect.”
Dandekar believes a compound like PEP005 that awakens and kills the AIDS virus has the potential to cure the disease.
Because it’s already approved by regulators for the treatment of skin conditions, the HIV activation agent could be used in human clinical trials very soon.