Shock and Kill
Despite the relapse, experts still find the Boston cases exciting because, they say, they are another step in the long and so-far-fruitless search for a cure. Dr. Deeks says they offer encouragement to ambitious future projects to genetically re-engineer infected patients' cells to be infection-resistant. At least two teams are already experimenting with variants on this idea.
He adds, “The big barrier to a cure is that there are cells that lie dormant, survive for decades, and contain hidden within them the virus. That is the primary limitation, and the primary goal of cure research is to get rid of it. One approach that is quite attractive to many investigators is this concept of ‘shock and kill.’ One uses a drug to shock the cells to force the virus out and then one hopes the cell will die, or one modifies the immune system to make sure all virus-producing cells die.” But, he says, “We are at the beginning of that, and we are just now starting with the shock part.”
In the shock-and-kill approach, he explained, the idea is to use a drug to shock the cells to force the virus out and then one hopes the cell will die, or one modifies the immune system to make sure all virus-producing cells die.
Dr. Deeks notes that several groups have presented data showing that “certain drugs that alter the DNA, that modify the chromatin that increase the cell's capacity to transcribe DNA, can, in fact, force the virus out of its hiding place. Whether that leads to any meaningful outcome, no one knows, but it proves the concept. At least the shock part, shocking it out of its hiding place, is theoretically possible.”
Recent reports suggested for example that histone deacetylase inhibitors (HDAC inhibitors) including vorinostat, belinostat, and givinostat, may be effective inducers of latent HIV expression. These inhibitors, scientists say, may offer a “unique opportunity to deplete the latent reservoir. An additional benefit is the anti-inflammatory properties of HDAC inhibitors including downregulation of HIV-1 coreceptor expression.”
But Anthony Fauci and colleagues at NIAID, in 2012, published studies demonstrating that HDACs do not induce HIV production in the latent viral reservoir of aviremic individuals suggesting that alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir.
The ultimate goal is, says Dr. Deeks, is finding a cure for HIV infection and AIDS disease. “We don't really want to have a handful of Berlin patients,” he says. “That's not going to change the world. We all want to cure people in a big way with drugs that could be given for a few months everywhere in the world. And the best prevention is to cure someone. If you are cured, you're not going to infect others.”