London patient becomes second known man cleared of HIV

Desiree Burns
March 10, 2019

Several patients who have received such transplants since Brown's successful treatment have died of the underlying cancer, several HIV researchers noted.

A team of researchers led by Ravindra Gupta, an infectious diseases physician at the University of Cambridge, UK, picked a donor who had two copies of a mutation in the CCR5 gene, which gives people resistance to HIV infection. His donor had a genetic mutation called CCR5 delta 2, which is resistant to HIV infection.

The researchers say it is too early to say the patient is "cured" of HIV.

More than 20 years after scientists announced that we had the medical resources to treat HIV effectively, around 40 percent of people living with HIV globally are still unable to access this life-saving treatment. When the cancers failed to respond to chemotherapy, doctors arranged for a bone-marrow transplant.

The first sustained remission survivor, announced in 2009 as "the Berlin patient" and later named as American Timothy Brown, was given two transplants and underwent total body irradiation to treat leukaemia - a process that almost killed him. This case may in time lead to the development of therapies that have less risk and a greater chance of successfully leading to HIV remission. That patient had a leukemia that could be treated with a blood stem-cell transplant, and his transplant team used cells that carried a mutation that eliminates one of the proteins that HIV uses to attach to cells.

This receptor was recently in the news after Chinese scientist He Jiankui claimed he'd edited the genes of embryos to include a protective version of CCR5.

The man continued on his antiretroviral regimen of dolutegravir (Tivicay), rilpivirine (Edurant) and lamivudine. In both cases, the donors' stem cells immediately began to attack the patients' immune cells.

The mutation is also rare in itself, meaning finding an exact match for every HIV patient may not be entirely possible. About 10 weeks post-transplant he developed mild graft-versus-host disease, which resolved on its own. This means that when populations are treated effectively we can also stop new infections.

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The man stopped antiretroviral therapy in an analytic treatment interruption 17 months after the transplant.

Reuters reports that the man, whose identity has not been revealed, has tested negative for the virus nearly three years after he received a bone marrow transplant from a donor with an HIV-resistant genetic mutation.

Brown said he would like to meet the London patient and would encourage him to go public because "it's been very useful for science and for giving hope to HIV-positive people, to people living with HIV", he told The Associated Press Monday. What's more, this current case shows that remission can happen without harsh conditioning chemotherapy or radiation.

What Gupta can confirm is that a stem cell transplant from a CCR5-negative donor can wipe out HIV and prevent the virus from rebounding.

Regular testing has confirmed that the patient's viral load remained undetectable since then.

The CCR5 gene was thrust into the global spotlight recently by the revelation that a Chinese scientist had attempted to edit human embryos to create the same deletion, with the hopes of creating babies that were immune to HIV.

Sixteen months after the treatment, he was taken off antiretrovirals. The transplant destroyed the cancer without harmful side effects, while the transplanted immune cells, which are now resistant to H.I.V., seem to have fully replaced his vulnerable cells, according to the paper. One possibility would be to alter the CCR5 gene, and thus compromise one of HIV's most prominent entry points into human cells.

Dr Anthony Fauci, head of the HIV/AIDS division at the National Institutes of Health, told the Daily Mail, we shouldn't expect this type of treatment to become the stock standard for people wanting a cure. "The hope is that lessons can be learned to help develop more widely applicable therapeutic approaches for attaining HIV remissions or cures".

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