The biggest hurdle to curing HIV lies in the virus’s ability to hide in reservoirs through out the body. Researchers have long feared that those reservoirs could include brain tissue, but this has been difficult to prove. As HIV researcher Dr. David Margolis once joked, people living with HIV haven’t been lining up to have their brains biopsied. Scientists have had to rely on autopsies, but even that route of exploration has been hampered because they couldn’t determine if the HIV particles found were actually in brain cells themselves or in the blood and other fluids surrounding them.
A new study, published in the journal AIDS has shown that HIV can indeed hide within brain cells—and that raises concern about how treatments can safely identify and fight the disease within our most sensitive organ.
"The potential for the brain to harbor significant HIV reservoirs that could pose a danger if activated hasn't received much attention in the HIV eradication field," Janice Clements, Ph.D., of the Johns Hopkins University School of Medicine said in a statement. "Our study sounds a major cautionary note about the potential for unintended consequences of the shock-and-kill treatment strategy."
To eradicate the disease from the body entirely, HIV curative therapies will have to attack the virus in the vital organs — and do so without harming those organs themselves.
In the current study, nonhuman primates with SIV (the monkey version of HIV) were given antiretroviral therapy until the virus was suppressed. After 400 days of viral suppression, the monkeys remained on ART but were then given ingenol-B, an unsuccessful attempt to "wake up" the virus in reservoirs.
"We didn't really see any significant effect," noted lead author Lucio Gama, "So we coupled ingenol-B with another latency-reversing agent, vorinostat, which is used in some cancer treatments to make cancer cells more vulnerable to the immune system."
Following a 10-day course of the combined treatment reactivated latent virus was detected in the animals’ plasma and tissues, including the brain. One monkey became sick with encephalitis, (inflammation of the brain) and was euthanized. The researchers drained the animal’s blood prior to vivisection, and then examined the brain, where they did find HIV.
Gama acknowledge that there was so little HIV in the brain that the researchers “almost missed it,” and they weren’t sure what caused the encephalitis; or whether it would have "resolved on its own."
One possibility (not addressed in the paper) is that the drug spurred the monkey’s immune system into attacking the monkey’s brain, and the resulting inflammatory response caused the encephalitis. This kind of unexpected, and potentially deadly side effect of drugs like is being seen in cancer patients treated with these drugs (read more here).
Gama emphasized the need for caution in adopting kick and kill strategies until we understand the side effects of waking up and eradicating HIV in reservoirs.