HIV Cure Could Cause Dangerous Adverse Events

Combination treatments have become especially popular for diseases, such as hepatitis C virus, cancer, and more. For HIV, combination treatments have been successful in achieving long-term disease control, despite not having an effective cure.

The goal of creating a cure for HIV has been hindered by the virus’ ability to hide in reservoir pools, which allows it to evade drugs. A new study published by AIDS suggests that a potential cure for HIV could damage the brain.

In the study, investigators tested the “shock and kill” proposed treatment strategy in macaques with simian immunodeficiency virus (SIV). This method uses latency-reversing agents that activate dormant viruses, which then makes them susceptible to the effects of the immune system.

It is hypothesized that by “waking up” these viruses, antiretroviral drugs would be able to kill a majority of HIV-infected cells, and potentially cure the patient. However, new findings suggest that this method could cause severe brain damage.

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

HIV research efforts in the past have mainly focused on creating prevention programs, and creating novel antiretroviral therapies that can transform the disease into a manageable chronic condition, according to the study.

In 2009, another team of researchers discovered that a patient was cured of HIV through a bone marrow transplant. The patient with HIV was given bone marrow from a donor whose genetics were naturally resistant to the disease.

Those recent findings sparked numerous research efforts to find a cure for HIV, with the shock and kill strategy created during this time.

Current researchers said that this method could pose serious health effects if HIV reservoirs exist in the brain. Prior to the creation of current antiretrovirals, numerous patients developed AIDS-related dementia, which suggests that HIV reservoirs do occur in the brain although it has not been proven.

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

However, no studies have definitively shown whether HIV reservoirs exist in the brains of patients undergoing long-term antiretroviral therapy, since autopsies do not indicate if the virus originated from brain cells or in the blood surrounding the brain, according to the current study.

Investigators analyzed the use of the shock and kill method in 3 pig-tailed macaque monkeys infected with SIV that had been receiving treatment with antiretrovirals for more than 12 months. The macaques remained on antiretroviral treatment throughout the study.

The researchers administered ingenol-B to 2 of the macaques to activate their virus, according to the study.

“We didn’t really see any significant effect,” Dr 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.”

After 10 days of this treatment, 1 macaque remained healthy, while the other developed encephalitis. In the macaque who displayed symptoms of encephalitis, a blood test revealed that it had an active HIV infection, according to the study.

Unfortunately, this macaque experienced disease worsening, and had to be euthanized by the scientists. Investigators then removed the macaque’s blood so they could examine the brain without any contamination from surrounding blood.

Interestingly, when tested, the brain only contained SIV in the occipital cortex, which processes visual information. Researchers said that the area containing SIV was so small they nearly missed it, according to the study.

Despite these findings, researchers caution that the results may not translate to humans with HIV, and may just be an occurrence in macaques with SIV. It could also be that the encephalitis could have resolved by itself.

The investigators concluded that their findings may indicate the need for additional precautions taken when looking for ways to completely eradicate HIV.