Online Extra: London case appears to be second HIV cure
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A London man who still has undetectable virus 30 months after stopping antiretroviral treatment is likely the second person ever cured of HIV, according to a report presented this week at the Conference on Retroviruses and Opportunistic Infections.
Two days before the conference was set to open in Boston, organizers decided to make the meeting virtual due to concerns about the coronavirus. Researchers gave their presentations via webcasts.
At last year's CROI, Dr. Ravindra Gupta of University College London reported that the so-called London Patient, who received a bone marrow transplant using stem cells from a donor with natural resistance to HIV, had no detectable virus in his blood plasma or T cells 18 months after stopping treatment.
At this week's meeting, Gupta said that an additional year of more extensive testing had found no functional HIV in the man's blood, lymph nodes, semen, gut tissue or cerebrospinal fluid.
"After 2.5 years off antiretrovirals and lack of evidence for any active virus, this almost certainly represents cure," Gupta told the Bay Area Reporter.
A day before Gupta's presentation, the New York Times revealed that the man, Adam Castillejo, 40, had decided to go public as the London Patient. Castillejo, who grew up in Venezuela, moved to London in 2002 and was diagnosed with HIV a year later. He is now leading a healthy and active life.
"My message to everyone out there living and coping with HIV is to not give up hope," Castillejo told the B.A.R. "I do hope that me going public will give some encouragement and empower people to keep breaking the stigma associated with HIV."
Resistant T cells
Like former San Francisco resident Timothy Ray Brown, known as the Berlin Patient — the only other person known to be cured of HIV — Castillejo underwent a bone marrow transplant to treat advanced cancer. According to the Times story, he spoke with Brown repeatedly before deciding to reveal his identity.
In both cases, doctors searched an international registry to find donors with double copies of an uncommon genetic mutation known as CCR5-delta-32, which makes T cells resistant to most types of HIV.
Brown received two stem cell transplants to treat leukemia in 2006, first undergoing strong chemotherapy and radiation to kill off his cancerous immune cells. He stopped antiretroviral therapy at the time of his first transplant, but his viral load did not rebound as expected. Over years of testing, researchers have found no functional virus anywhere in his body. Brown has now been free of HIV for more than 13 years.
Castillejo was diagnosed with lymphoma in 2011. After five years of grueling treatment, he underwent a bone marrow transplant in May 2016. But he received less aggressive chemotherapy than Brown and was able to stay on antiretroviral therapy.
The transplant led to complete remission of his lymphoma. Post-transplant tests showed that most of his T cells now lacked the CCR5 receptors HIV uses to enter the cells. In September 2017, with no evidence of viable HIV in his blood, he stopped his antiretrovirals in a closely monitored analytic treatment interruption.
When Castillejo was last tested on March 4, his plasma viral load remained undetectable using an ultrasensitive assay. Viral load was also undetectable in his semen and cerebrospinal fluid surrounding the brain and spinal cord. Biopsies showed no evidence of functional HIV in a lymph node or in his large or small intestine. Some bits of HIV genetic material were detected in long-lived memory T cells, but Gupta said these are probably "fossils" that cannot trigger active viral replication.
If this does prove to be a second cure, experts caution that the high-risk procedure will not be an option for people with HIV who do not need the treatment for cancer. But researchers are working on ways to mimic the same effect using gene therapy to delete CCR5 receptors from T cells or stem cells that give rise to all immune cells.