8 July 2019

Africa: Hope for HIV Cure As New Drug is Successful in Mice

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Could a cure for HIV be on the horizon? This is the question many are asking following new research that shows 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 referred to simply as Laser ART. The second treatment involves the removal of viral DNA using a gene editing tool called CRISPR-Cas9. A combination of the two methods eliminated the virus from nine mice.

EXPERIMENT

Using 29 mice, a team of research combined gene-editing technology (CRISPR) and Laser ART to erase HIV DNA from the genomes of the animals in what they call an unprecedented study that was published Tuesday in the journal Nature Communications.

"This is the first step towards showing, to my knowledge, that HIV is a curable disease," said one of the study's lead authors, Kamel Khalili, and the director of the Centre for Neurovirology and the Comprehensive NeuroAIDS Centre at Temple University's Lewis Katz School of Medicine.

In the first stage involving Laser ART, traditional anti-HIV drugs are tweaked so they develop a crystal structure, and are then encased in fat-soluble particles. This helps the drugs slip through the membranes of cells in places where HIV tends to hide, including the liver, lymph tissue and spleen. The cells' enzymes start to release the drug. This not only targets viral sanctuaries but also maintains HIV replication at low levels for extended periods of time, reducing the frequency of ART administration.

The crystal structure releases the drugs more slowly, allowing them to continue killing off dormant viruses as they start to emerge and replicate for months rather than days or weeks, like the conventional forms of the medicines. After the Laser ART treatment, researchers then splice out HIV from any circulating cells that are infected with viral genes using the CRISPR-cas9.

The team involved 35 scientists (from two American universities -- University of Nebraska Medical Centre (UNMC) and the Lewis Katz School of Medicine. A Kenyan, Dr Benson Edagwa, an assistant professor of pharmacology at the UNMC was part of the team.

LASER ART

Laser ART is a "super" form of ART that keeps replication of the virus at low levels for longer time periods, according to co-author Howard Gendelman, chair of UNMC's pharmacology and experimental neuroscience department, and director of the Centre for Neurodegenerative Diseases.

"We are going to the root cause. We are going after the virus that's already integrated in the genome of the host cell," said Dr Gendelman.

The study authors said the findings are promising and they are now testing the CRISPR-Laser ART combination on primates. The breakthrough gives hope to some 37 million people worldwide living with HIV.

However, Dr Gendelman said there is still much work to be done before the method can be tested on humans.

"We are at the cusp of a scientific revolution in human genomes that can change the course, quality and longevity of life. Things that work in mice, may not work in men," he said. "The limitations of any mouse work have to do with the species, how the drug is administered, and the distribution, which is a lot easier than a man or a woman."

It is half a century since the first known HIV-related death occurred and two patients have since been declared "functionally cured" after the virus went into remission.

On March 4, a team of UK-based researchers announced they had successfully treated the "London patient," after he received a bone marrow transplant. He became the second man to be declared HIV-free. The first case in 2007 involved an American, Timothy Brown or the "Berlin patient" who underwent similar treatment in Germany. On March 5, a different group of researchers announced a possible third case -- the "Düsseldorf patient," who was declared HIV-free after receiving a bone marrow transplant.

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