The HIV “Shock and Kill” Method Could Backfire

Although antiretroviral therapy (ART) has been widely successful in keeping patients with the human immunodeficiency virus (HIV) alive long with better quality of life, finding a cure for the disease remains challenging. Researchers have been exploring the “shock and kill” method to get rid of the virus for good, but a new study warns that the strategy could make things even worse.

HIV has the ability to hide in cells and become dormant for long periods of time. Therefore, it’s been the goal to find a way to wake up those dormant viruses and wipe them out. The shock and kill method is a potential way to do just that. The problem, however, is that a team from the Johns Hopkins University of Medicine found that it could backfire in the brain, and studies have already highlighted cognitive decline as an HIV complication.

“Our study sounds a major cautionary note about the potential for unintended consequences of the shock-and-kill treatment strategy,” Janice Clements, PhD, professor of molecular and comparative pathobiology at Johns Hopkins, said in a news release.

Using simian immunodeficiency virus (SIV) — referred to as HIV’s close cousin – in macaques, the researchers looked deeper into the potentially dangerous outcomes in the brain associated with the treatment.

When it comes to patients with HIV on long-term treatment, no study has confirmed whether significant reservoirs of dormant viruses are hiding in the brain. This is partly because autopsies haven’t been able to determine if the virus in the brain comes from brain cells or surrounding blood.

“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,” Clements said.

Two of the three SIV-infected pig-tailed macaque monkeys were given 0.4 mg/kg ingenol-B — an agent believed to wake up the virus – per day for 30 days. But when no significant effect occurred, “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,” explained Lucio Gama, PhD, assistant professor of molecule and comparative pathobiology at Johns Hopkins.

After 10 days, mne monkey stayed healthy on the combination treatment. However, the other monkey developed encephalitis (brain inflammation) symptoms. The sick monkey continued to worsen, so after it was put down, the blood was removed from its body so it wouldn’t contaminate the analysis of its brain.

SIV was found to still be in the brain, but only in the occipital cortex — the section which processes visual information. But it was so small that the researchers almost missed it.

Gama warned that this evidence may not directly relate to HIV in humans. But regardless, it shows the importance of being extra careful when exploring ways to eradicate dormant viruses.

The full study, “Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques” can be found in the journal AIDS.

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