Temple Research Team Claims Success in HIV Removal

Researchers at Temple University believe they have found a way to help remove any traces of HIV-1 from a person’s body as work continues toward a cure for the virus.

In a study published in Proceedings of the National Academy of Sciences, Kamel Khalili, PhD, a professor at the school and chairman of the Department of Neurosciences, announced the findings of his work with Wenhui Hu, MD, PhD, an associate professor of neuroscience and a team of researchers. The work focused on finding ways for doctors to physically remove HIV-1 genes from a patient’s body.

“It’s an exciting discovery, but it’s not yet ready to go into the clinic,” Khalili said in a statement released by Temple University School of Medicine. “It’s a proof of concept that we’re moving in the right direction.”

Khalili, who also serves as the Director of the Center for Neurovirology and Director of the Comprehensive NeuroAIDS Center at the university, and Hu used molecular tools to cut out the HIV-1 proviral DNA.

The statement from the school said the research team used a combination of a DNA-snipping enzyme called a nuclease and a strand of guide RNA (gRNA). The end result allows cells to fix themselves and remove the virus to help improve the patient’s health.

“Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease,” Khalili noted.

Up until this point many HIV-1 patients have seen success with highly active antiretroviral therapy (HAART). Even with this success, because the virus lingers in the body, it can come back strong with any break in treatment, the statement said.

“The low-level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with aging,” Khalili said.

Potential problems cited by Khalili include cardiomyopathy, bone and kidney diseases, as well as neurocognitive disorders. “These problems are often exacerbated by the toxic drugs that must be taken to control the virus.”

As part of the study, Khalili’s team developed a 20-nucleotide strand of gRNA to pair with Cas9. The goal was then to attack the long terminal repeat (LTR) portions of a gene. Using Cas9, the researchers were able to remove the 9,709 nucleotides of the HIV-1 genome. Special attention was paid to not use nucleotide sequences that appear in the coding of a human DNA strand.

Khalili said the virus was removed in microglia, macrophages, and T-lymphocytes. “T-cells and monocytic cells are the main cell types infected by HIV-1, so they are the most important targets for this technology.”

In the statement, the team said there is still a lot more work to be done, including working to ensure that all infected cells are targeted by the treatment and studying the impact of gene mutations on its success.

“We are working on a number of strategies so we can take that construct into preclinical studies,” Khalili said. “We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it.”

The professor also said he believes the work could be a first step in helping patients with other viruses as well as the combination used in this study was able to work through the difficulties of tackling the HIV-1 strands.