In what could be a potential cure for HIV, scientists have revealed how a sequence of two treatments could completely remove the virus causing HIV from the body of 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.

Researchers at Temple University in Philadelphia in the US claim they have successfully tested the treatment on a mouse model of human HIV. Of the mice that received LASER antiretroviral therapy followed by gene editing, the virus was found to have been eliminated from cell and tissue reservoirs in up to a third of infected animals. In contrast, treating mice with either LASER antiretroviral therapy or gene editing — but not both — resulted in viral rebound in 100 percent of treated infected animals.

The big message from this research is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER administered together, to produce a cure for HIV infection.

According to the most recent figures from UNAIDS, worldwide, 36.9 million people were living with HIV in 2017, even as 1.8 million new cases of HIV were added to the growing number of HIV patients in the world. 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 three 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 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 lifelong 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.

Researchers 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. LASER antiretroviral therapy differs from conventional antiretroviral therapy in that its drugs take the form of nanocrystals that can quickly make their way into tissues harboring dormant HIV. Once inside HIV-affected cells, the nanocrystals can slowly release their payload over several weeks.

They tested the approach in mice with human T cells that could easily contract HIV and in which the virus became dormant following interrupted antiretroviral therapy treatment. The team treated the mice with LASER antiretroviral therapy followed by CRISPR-Cas9 and then examined their HIV viral load. various tests detected no trace of HIV DNA in around one-third of the animals.

We now have a clear path to move ahead to trials in nonhuman primates and possibly clinical trials in human patients within the year, said a lead researcher.


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