HIV cure must offer big step forward to replace drugs, experts say

Scientists use cutting-edge genetic technique to remove virus from lab-grown cells

Scientists have used gene-editing technology called CRISPR-Cas to remove HIV from cells. AP

Efforts to rid the body of HIV using a cutting-edge genetic technique have a high hurdle to cross to be better than controlling the infection with drugs, a leading doctor has said.

Dr Andrew Freedman, a reader in infectious diseases at Cardiff University in the UK, said that existing treatments were so effective that an experimental approach using gene editing technology may struggle to offer an improvement.

His comments came after scientists from Amsterdam University Medical Centre said that they had used gene-editing technology called CRISPR-Cas to purge cells of HIV – the virus that causes Aids – in the laboratory.

Their findings are due to be presented next month in Barcelona at the European Congress of Clinical Microbiology and Infectious Diseases, which described the research as “a significant breakthrough in the search for an HIV cure”.

Any potential use on patients is likely to be years away.

Dr Freedman, who has more than three decades of experience as a researcher and clinician involved with HIV, said that if a “safe and affordable” cure were to be developed, it could be a step forward.

However, he said that HIV infections could currently be effectively controlled.

“The alternative [to any potential cure] is lifelong antiretroviral treatment. This treatment is well tolerated and simple, with one pill a day. It’s a high bar for a cure to clear before its going to replace treatment,” he said.

“Certainly it would be better than actual lifelong treatment if it was safe and effective and affordable.”

No longer a death sentence

While an HIV infection was once considered tantamount to a death sentence, drugs are now effective enough to mean that the virus can be controlled. The life expectancy of those with access to treatment, and who take the drugs as instructed, is similar to those who are not infected.

An estimated 76 per cent of people living with HIV are on antiretroviral therapy, with men less likely than women to have access to the drugs, according to the UN.

In 2022, according the UN figures, 1.3 million people were newly infected with HIV. Since HIV emerged about 85 million people have been infected, about 40 million of whom have died.

HIV infections had risen by 31 per cent in the past two decades in the Mena region, according to a report from pharmaceutical company AstraZeneca, also released in 2022.

CRISPR-Cas is a relatively new technology that uses what has been described as molecular scissors to enable precise changes to be made to an organism’s genetic material. Particular sections of DNA can be targeted for removal or alteration.

The development of CRISPR-Cas technology, which is derived from bacteria, resulted in two researchers, Emmanuelle Charpentier and Jennifer Doudna, being awarded the Nobel Prize in Chemistry in 2020.

They had discovered “one of gene technology’s sharpest tools”, one that had “revolutionised the molecular life sciences” and created advances in fields such as plant breeding and cancer therapy, Nobel said.

For cancer, it has been employed experimentally to cut out genes that are overactive in cancer cells, causing tumours to die.

For HIV, CRISPR-Cas technology appears able to rid cells of the virus even though it incorporates its own genetic material into that of its host.

The virus may remain dormant if a person is on antiretroviral treatment but can re-emerge from T cells, a type of immune system cell, if drugs are stopped.

After trying various methods involving different CRISPR-Cas systems, the researchers behind the new study removed the viral DNA from the genetic material in laboratory-grown T cells, curing the cells of the infection.

“We have developed an efficient combinatorial CRISPR-attack on the HIV in various cells and the locations where it can be hidden in reservoirs, and demonstrated that therapeutics can be specifically delivered to the cells of interest,” they said.

“These findings represent a pivotal advancement towards designing a cure strategy.”

Challenges ahead

Dr Freedman described efforts to develop an HIV cure as “very challenging”, with only a small number of people cured so far after receiving a bone-marrow transplant from individuals carrying a mutation that made them resistant to the virus.

Given the risks involved, an approach to achieve a cure is not considered suitable for HIV patients who do not already require a bone-marrow transplant.

Before the latest CRISPR-Cas research, other scientists had used the technology to remove HIV from cells, with the new study “just trying out different delivery methods”, Dr Freedman said.

“It’s good work but we’re nowhere close to this being applied to humans,” he said of the new study, which has not yet been peer reviewed.

A San Francisco company called Excision Biotherapeutics has started clinical trials of its own therapy using CRISPR-Cas in the hope of achieving what is described as a functional cure for HIV infections.

While praising the technology as “the most accurate way to currently modify a genome”, Ian Jones, a professor of virology at the University of Reading in the UK, said that it would be “a tall order” for HIV to be removed from all cells of infected individuals.

Also, he said that it would be difficult to roll out any potential cure based on CRISPR-Cas technology on a sufficient scale, especially in regions like sub-Saharan Africa, which is home to around two-thirds of the estimated 39 million currently living with HIV.

“CRISPR technology would be something that might be applied to a handful of people in a very expensive American clinic. The idea this would be a mass treatment would be a non-starter. You just cannot deal with these numbers,” he said.