World first: Researchers completely remove HIV from mice
Could a cure for HIV be in sight? New research has revealed how a sequence of two treatments could completely remove the virus in mice.
The first treatment is a long-acting slow-effective release (LASER) form of antiretroviral therapy.
The second treatment involves the removal of viral DNA using a gene editing tool called CRISPR-Cas9.
In a recent Nature Communications paper, the researchers describe how they tested the two-step approach in a mouse model of human HIV.
Of the mice that received LASER antiretroviral therapy followed by gene editing, the "virus was eliminated from cell and tissue reservoirs in up to a third of infected animals," note the authors.
In contrast, treating mice with either LASER antiretroviral therapy or gene editing — but not both — "resulted in viral rebound in 100% of treated infected animals."
"The big message of this work," says co-senior study author Kamel Khalili, Ph.D., of the Lewis Katz School of Medicine (LKSOM) at Temple University in Philadelphia, PA, "is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER [antiretroviral therapy], administered together, to produce a cure for HIV infection."
Khalili is a professor in LKSOM's department of neuroscience and its chair. He is also the director of LKSOM's Center for Neurovirology and of its Comprehensive NeuroAIDS Center.
HIV can hide in a dormant state
According to the most recent figures from UNAIDS, worldwide, 36.9 million people were living with HIV in 2017. In the same year, around 1.8 million contracted the virus.
HIV spreads when a person comes into contact with infected bodily fluids from another person. It progressively weakens the immune system by attacking cells that defend against infection and replicating inside them.
People with HIV who do not receive treatment have a high risk of developing AIDS, an advanced state of immune system damage. People with AIDS typically survive for no longer than 3 years without treatment.
HIV attacks CD4, or T helper, cells, which are a type of white blood cell that helps regulate immune responses to infection.
The virus fuses with the T helper cell, takes over its DNA, and forces the cell to make copies of HIV. When the copies are ready, the cell releases them into the bloodstream, from which point they can go on to infect more cells and start the process over again.
Antiretroviral therapy can halt, not kill, HIV
Antiretroviral therapy is a combination of drugs that stop the progress of HIV by targeting different stages of the virus's lifecycle.
Many people with HIV who receive antiretroviral therapy and adhere to their treatment regimen can expect to live a long life in good health. However, antiretroviral therapy does not rid the body of HIV, so people have to keep taking the drugs to prevent the development of AIDS.
If a person stops antiretroviral therapy, HIV can flare up again and continue its life cycle. This is because the virus inserts its genetic material into the genomes of the immune cells that it infects. This ability allows HIV to hide quietly in a place that antiretroviral therapy cannot reach.
In a 2017 study, Prof. Khalili and team described how they used CRISPR-Cas9 gene editing to remove HIV genetic material from the DNA of infected cells to massively reduce viral load. However, like antiretroviral therapy, gene editing by itself does not completely remove all traces of HIV.
Their new study describes how LASER antiretroviral therapy targets HIV in its "viral sanctuaries" and drip feeds it with drugs that suppress the virus's ability to replicate.
