London Patient Cured of HIV! It may even seem that way. But, despite continuing to have no detectable HIV, this fact hasura of HIV? After all, thirty months after stopping antiretroviral therapy, according to a report by the Conference on Retroviruses and Opportunistic Infections (CROI 2020).
The research is being presented virtually this week after the Boston meeting was canceled due to the coronavirus crisis.
Healing HIV in this case
In 2016, the man underwent a bone marrow transplant to treat lymphoma using stem cells from a donor with natural resistance to HIV. Since he stopped treatment, researchers have been unable to find functional HIV in his blood, semen, lymph nodes, intestinal tissue or cerebrospinal fluid.
Professor Ravindra Gupta, from University College London, presented the case for the first time at CROI last year. At that point, the man was free of detectable viruses for 18 months after stopping treatment.
With or without HIV Cure I, Cláudio affirm: Not losing hope is fundamental
Yesterday, o New York Times revealed that the man, Adam Castillejo, had decided to make the “London patient” public.
"My message to everyone living and dealing with HIV is not to lose hope," Castillejo told aidsmap.com. "I hope that I will go public and give some encouragement and enable people to continue breaking the stigma associated with HIV."
Last year, Gupta said that after two or three years without a detectable virus, it would be appropriate to talk about a cure, adding that he was "highly confident that this will be achieved". And, in fact, he told aidsmap.com this week: “After 2,5 years without antiretrovirals and a lack of evidence of any active viruses, this almost certainly represents healing".
The latest findings strongly suggest that Castillejo joined Timothy Ray Brown, formerly known as Berlin patient, as the second person to permanently defeat HIV.
HIV Cure can go through the lack of CCR5 co-receptors
Brown received two stem cell transplants to treat leukemia in 2006. The donor had double copies of an unusual genetic mutation known as CCR5-delta-32, which results lack of CCR5 co-receptors on T cells, the gateway most types of HIV use to enter cells. He underwent intensive chemotherapy and radiation to kill his cancerous immune cells, allowing donor stem cells to rebuild a new HIV-resistant immune system.
As described in the 2007 CROI, Brown stopped antiretroviral therapy at the time of his first transplant, but his viral load did not recover. The researchers extensively tested their blood, gut, brain and other tissues, finding no evidence of HIV capable of replication anywhere in the body. Brown has been HIV-free for more than 13 years.
Castillejo was diagnosed with Hodgkin's lymphoma in 2011. After five years of exhausting but futile treatment, he underwent a bone marrow transplant in May 2016. Like Brown, he received stem cells from donors with a double mutation in CCR5 -delta-32. However, he underwent less aggressive conditioning chemotherapy and was able to remain on his antiretroviral regimen of dolutegravir, rilpivirine and lamivudine.
The transplant led to remission of lymphoma, but there were adverse reactions
Fortunately, the transplant led to complete remission of his lymphoma. About ten weeks after the transplant, he developed a mild graft-versus-host disease, a condition in which newly transplanted immune cells attack the recipient's body.
Post-transplant tests showed that most of her CD4 T cells now lacked CCR5 receivers. Extensive tests of blood plasma and T cells have failed to detect functional viruses. In September 2017, still without evidence of Viable HIV, Castillejo discontinued antiretroviral therapy in a closely monitored analytical treatment interruption.
When last tested on March 4, 2020 - 30 months after stopping antiretrovirals - its plasma viral load remained undetectable using an assay with a detection limit of 1 copy / ml of HIV RNA, Gupta reported on a poster at CROI and in March 10, 2020 edition of Lancet HIV.
In addition, the viral load was undetectable in the semen and cerebrospinal fluid around the brain and spinal cord. Intestinal biopsies showed that HIV DNA was not found in samples from the rectum, sigmoid colon or ileum (part of the small intestine). Tissue from an armpit lymph node negative for intact proviral DNA, the genetic model that HIV inserts into host cells.
Very low level of HIV remnants (irrelevant)
The tests showed "a very low positive signal" for HIV DNA in T cells of peripheral CD4 memory at 28 months, but these fragments of genetic material are believed to be essentially "fossils" that cannot trigger viral replication active.
HIV-specific CD4 and CD8 T cell responses remained absent at 27 months. Levels of HIV-specific antibodies are low and continue to fall, suggesting that the remaining fragments of the virus are not stimulating an immune response.
Castillejo CD4 cell recovery has been a little slow, the last step in 430 cells / mm3, which may be due to the persistent effects of chemotherapy or a long duration of untreated HIV before starting antiretroviral therapy.
Based on mathematical modeling, Gupta and colleagues calculated that the probability of “lifetime remission” is 99% if at least 90% of HIV-susceptible cells retain the donor's CCR5-delta-32 mutation, known as chimerism. When last tested, chimerism was maintained in 99% of Castillejo's peripheral T cells, suggesting that the cure is "Almost certain".
However, in an editorial accompanying Dr. Jennifer Zerbato and Professor Sharon Lewin, from the Doherty Institute in Melbourne, they took a more cautious stance, writing: “The additional data provided in this follow-up case the report is certainly exciting and encouraging, but in the end, only time will tell. ”
O Transplanting stem cells CCR5-delta-32 involves too high a risk. Not acceptable
Experts warn that even if the CCR5-delta-32 stem cell transplant leads to a functional cure, this high-risk procedure will not be an option for people with HIV who do not need cancer treatment.
Maybe genetic editing
However, researchers are working on several approaches to mimic the same effect, using the gene therapy to exclude CCR5 receptors of an individual's T cells or stem cells that give rise to immune cells.
March 10, 2020
Gupta RK et al. Sustained HIV remission in London patient: the case for HIV cure. Conference on Retroviruses and Opportunistic Infections, summary 346LB, March 2020.
Gupta RK et al. Evidence for the cure of HIV-1 after transplantation of allogeneic hemopoietic stem cells CCR5Δ32 / Δ32 30 months after stopping the analytical treatment: case report. The Lancet HIV, online before printing, March 2020.