March 6, 2019 / 2:49 PM / 7 months ago

World's second man cleared of AIDS virus invigorates quest for cure

LONDON/CHICAGO (Reuters) - Scientific investigation into the world’s second man cleared of the AIDS virus is zooming in on a gene and a treatment side-effect, as newly-enthused researchers strive to find a cure for the disease that has killed millions.

FILE PHOTO: A nurse (L) hands out a red ribbon to a woman, to mark World Aids Day, at the entrance of Emilio Ribas Hospital, in Sao Paulo December 1, 2014. REUTERS/Nacho Doce/File Photo

Known as the “London Patient”, the man had HIV and a type of blood cancer called Hodgkin’s lymphoma. He responded successfully to a bone marrow transplant from a donor with rare genetic resistance to HIV infection.

The transplant cleared the man’s cancer and his HIV, but the resistant genes may not be the sole cause of his HIV remission.

Since the pandemic began in the 1980s, more than 70 million people have been infected with HIV and about 35 million have died, most in Africa. Medical advances mean tests can detect HIV early, new drugs can control it, and there are ways to stop it spreading - but 37 million people still live with the virus.

The London Patient’s case gives fresh hope to scientists and pharmaceutical researchers who have spent decades looking for ways to end AIDS. HIV expert Sharon Lewin said two factors were probably at play in his success story: the genetic resistance and a transplant side-effect that attacks immune cells.

“The new bone marrow is resistant to HIV, and also the new bone marrow is actively eliminating any HIV-infected cells through something called ‘graft versus host’ disease,” said Lewin, co-chair of the International AIDS Society’s cure research advisory board and a researcher at Australia’s Doherty Institute.

The London Patient joins the first case of this kind, Timothy Ray Brown - or the “Berlin Patient” - whose HIV was eradicated by a similar transplant treatment in 2007. It involved the destruction of his immune system and transplanted stem cells with a gene mutation called CCR5 that resists HIV.

The AIDS virus uses CCR5 to enter cells, but if the gene is mutated, HIV cannot latch onto cells and infect them.

This “graft versus host” effect is akin to a deadly battle of two immune systems, explained Steven Deeks, an HIV expert at the University of California. The incoming transplanted donor-immune cells seek out and destroy all the host’s immune cells - including those in which HIV can hide out, he said.

“The transplant resulted in the complete destruction of the old immune system and the construction of a new immune system in which the (HIV) virus can’t replicate (because of the genetic mutation). That is the cure,” Deeks told Reuters.

“LONG WAY TO GO”

But such transplants are complex, expensive and highly risky to the patients, who would run a risk of dying in the process.

“So the key is that someone has to come up with a way to deliver (CCR5) gene-editing capability to all the (immune system) T-cells - and that’s what people are working on right now,” Deeks added.

Teams in labs around the world, as well as drug companies including Gilead Sciences, Johnson & Johnson and GSK’s ViiV Healthcare, have very early-stage cure studies in the works, said Rowena Johnston, director of research at U.S. AIDS research foundation amfAR.

“Companies dip their toes in and out of cure research.”

But the idea of looking for a cure involving bone marrow transplants to destroy and replace the immune systems of all those infected with HIV is a non-starter.

Many patients currently have good control of their disease with treatments such as Gilead’s anti-retroviral drug Biktarvy, which combines three HIV medicines in a single daily tablet.

“I’d rather be on the single pill a day with very little toxicities than risk something as draconian as a transplant,” said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases.

He and others said the London Patient’s case does, however, underline that in this approach, two factors combined are crucial - the CCR5 genetic resistance, plus its delivery to all cells, including immune cells.

Some research teams in the United States and elsewhere are developing gene-editing techniques to edit CCR5 cells outside of the body and reintroduce the edited cells back to patients.

Specialists said this method has its limits, because it only edits some cells and leaves native wild type cells untouched in the body where HIV can still hide.

Other avenues are also being explored.

Dan Barouch, a vaccine researcher at the Harvard-affiliated Beth Israel Deaconess Medical Center in Boston, is working with Gilead to develop what’s known as a “kick and kill” treatment.

FILE PHOTO: Buddhist monks light candles during an HIV/AIDS awareness campaign on the occasion of World AIDS Day in Kolkata, India, December 1, 2018. REUTERS/Rupak De Chowdhuri -/File Photo

The idea is to use an initial drug to flush out HIV that is hiding from the immune system and then use standard antiretrovirals to kill the newly-exposed virus. Animal studies have shown hope, but it has not yet been proven in people.

“All HIV cure approaches in general are in their infancy,” he said in a telephone interview.

Rare cases of remission, such as the London and Berlin patients “provide a lot of enthusiasm and motivation” for research teams and show that a cure can be achieved, he said, “but we still have a long way to go”.

Writing by Kate Kelland; Editing by Andrew Cawthorne

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