UK man the second to be cleared of the Aids virus

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An HIV-positive man in Britain has become the second known adult worldwide to be cleared of the Aids virus after he received a bone marrow transplant from an HIV resistant donor, his doctors are quoted in a Physicians Weekly report as saying. Almost three years after receiving bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection – and more than 18 months after coming off antiretroviral drugs – highly sensitive tests still show no trace of the man’s previous HIV infection.

“There is no virus there that we can measure. We can’t detect anything,” said Ravindra Gupta, a professor and HIV biologist who co-led a team of doctors treating the man.

The case is a proof of the concept that scientists will one day be able to end Aids, the doctors said, but does not mean a cure for HIV has been found. Gupta described his patient as “functionally cured” and “in remission”, but cautioned: “It’s too early to say he’s cured.”

The report says the man is being called “the London patient”, in part because his case is similar to the first known case of a functional cure of HIV – in a us man, Timothy Brown, who became known as the Berlin patient when he underwent similar treatment in Germany in 2007 which also cleared his HIV. Brown, who had been living in Berlin, has since moved to the US and, according to HIV experts, is still HIV-free.

The report says some 37m people worldwide are currently infected with HIV and the Aids pandemic has killed around 35m people worldwide since it began in the 1980s. Scientific research into the complex virus has in recent years led to the development of drug combinations that can keep it at bay in most patients.

The report says Gupta, now at Cambridge University, treated the London patient when he was working at University College London. The man had contracted HIV in 2003, Gupta said, and in 2012 was also diagnosed with a type of blood cancer called Hodgkin’s Lymphoma.

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him. “This was really his last chance of survival,” Gupta is quoted in an interview as saying. The donor – who was unrelated – had a genetic mutation known as ‘CCR5 delta 32’, which confers resistance to HIV.

The transplant went relatively smoothly, Gupta is quoted in the report as saying, but there were some side effects, including the patient suffering a period of “graft-versus-host” disease – a condition in which donor immune cells attack the recipient’s immune cells.

Most experts say it is inconceivable such treatments could be a way of curing all patients. The report says the procedure is expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people – most of them of northern European descent – who have the CCR5 mutation that makes them resistant to the virus.

Specialists said it is also not yet clear whether the CCR5 resistance is the only key – or whether the graft versus host disease may have been just as important. Both the Berlin and London patients had this complication, which may have played a role in the loss of HIV-infected cells, Gupta said.

Sharon Lewin, an expert at Australia’s Doherty Institute and co-chair of the International AIDS Society’s cure research advisory board, is quoted in the report as saying London case points to new avenues for study. “We haven’t cured HIV, but (this) gives us hope that it’s going to be feasible one day to eliminate the virus,” she said.

Gupta said his team plans to use these findings to explore potential new HIV treatment strategies. “We need to understand if we could knock out this (CCR5) receptor in people with HIV, which may be possible with gene therapy,” he said.

The report says the London patient, whose case was set to be reported in the journal Nature and presented at a medical conference in Seattle, has asked his medical team not to reveal his name, age, nationality or other details.

Abstract
HIV-1 cure remains elusive with only one reported case a decade ago1,2. Termed the ‘Berlin patient’, the individual underwent two allogeneic haematopoietic stem-cell transplantation (allo-HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Critically, it is unclear which treatment or patient parameters contributed to this only documented case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An HIV-1-infected adult underwent allo-HSCT for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft versus host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained through a further 18 months. Plasma HIV-1 RNA has been undetectable at less than 1 copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assay from peripheral CD4 T lymphocytes shows no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic viruses were identified in HIV-1 DNA from CD4 T cells of the patient prior to transplant. CD4 T cells isolated from peripheral blood post-transplant did not express CCR5 and were only susceptible to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus (CMV)-specific responses were detectable. Likewise, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, these data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings further support the development of HIV remission strategies based on preventing CCR5 expression.

Authors
Ravindra K Gupta, Sultan Abdul-jawad, Laura E McCoy, Hoi Ping Mok, Dimitra Peppa, Maria Salgado, Javier Martinez-Picado, Monique Nijhuis, Annemarie MJ Wensing, Helen Lee, Paul Grant, Eleni Nastouli, Jonathan Lambert, Matthew Pace, Fanny Salasc, Christopher Monit, Andrew Innes, Luke Muir, Laura Waters, John Frater, Andrew ML Lever, SG Edwards, Ian H Gabriel, Eduardo Olavarria

Physicians Weekly report
Nature abstract


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