Risks Associated with Shock and Kill HIV Treatment Strategy

The “shock and kill” strategy for treating HIV may cause more harm than good if the virus is hiding in the brain, according to a recent study.

Finding a cure for HIV is an ongoing issue because of the virus’ ability to hide in cells and remain dormant. But a new strategy, known as “shock and kill” involves latency-reversing agents that wake up the dormant viruses in the body, making them vulnerable to the immune system. The hope is that combining this method with antiretroviral treatment (ART) it could wipe out most of the infected cells.

However, in a study of SIV-infected macaques, investigators found that this strategy could cause potentially harmful brain inflammation. The findings were published in AIDS.

“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,” said investigator Janice Clements, PhD. “Our study sounds a major cautionary note about the potential for unintended consequences of the shock and kill treatment strategy.”

There is evidence that HIV reservoirs exist in the brain, as evidenced by the many cases of AIDS-related dementia that occurred before ART was developed.

“Research had also shown that HIV can infect monocytes in the blood, which we know cross into the brain,” said lead author Lucio Gama, PhD.

For the study, researchers used 3 pig-tailed macaque monkeys infected with SIV, and treated them with ART for more than a year. Two of the macaques were given the latency-reversing agent, ingenol-B, to wake up the dormant virus.

“We didn’t really see any significant effects,” Gama said. “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.”

Additionally, the macaques continued their course of ART throughout the experiment, according to the study.

The results showed that after a 10-day course of combined treatment, 1 of the macaques remained healthy, while the others developed symptoms of encephalitis. Blood tests revealed an active SIV infection.

Once the disease worsened, the investigators humanely killed the macaques and withdrew the blood from the body, according to the study. This was to ensure that the blood sources of the virus would not muddle their examination of the brain.

After testing, the investigators found that SIV was still present in the brain. However, it was only present in 1 of the regions analyzed, the occipital cortex, which processes visual information. The authors said that the infected area was so small that they almost missed it.

The investigators cautioned that the results of the study may not apply to HIV-infected humans. Furthermore, it’s also possible that the encephalitis was transient and could have been resolved by itself. However, the authors concluded that their findings indicate the need for extra caution when it comes to exploring ways to flush out HIV reservoirs to eradicate the virus from the body.