O Patient from London is in “long term remission” for HIV infection - This may seem like a cure. But scientists call for caution.A London man has remained undetectable to HIVLondon man has remained undetectable to HIV for a year and a half after undergoing a bone marrow stem cell transplant to treat lymphoma; Presearchers reportsRAM this week in Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle.
Ravindra Gupta, now at the University of Cambridge, will present the case on Tuesday, but after a premature embargo, many media outlets have released the results in advance, suggesting that the case represents a second cure for HIV, similar to that of Timothy Ray. Brown, known as the patient of Berlin.
Brown - The first and so far only person known to have been cured of HIV - has 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 (I, Claudio, have a person close to me who can not avoid the contagion) that results in the lack of co-CCR5, receptors on T cells, the gateway that most types of HIV used to infect cells. He underwent intensive chemotherapy and whole body radiation to kill his cancerous immune cells, allowing donor stem cells to rebuild a new HIV-resistant immune systema new immune system resistant to HIV.
As described in the 2007 CROI, Brown discontinued antiretroviral therapy at the time of his first transplant, but his viral load did not recover. Researchers have extensively tested their blood, gut, brain and other tissues, finding no evidence of competent HIV replication in any part of their body. This week, Brown celebrated 12 years without HIV in a community healing workshop before the conference.
Other attempts to discontinue antiretroviral therapy in HIV-positive bone marrow transplant recipients were less successful. Timothy Henrich, now at the University of California, San Francisco, and colleagues attempted to replicate Brown's cure in two Boston cancer patients, but in these cases donors had normal or wild-type stem cells that remained susceptible to HIV, they received less chemotherapy and remained on antiretroviral therapy.
After no HIV could be detected in their blood and tissues for years, the men underwent closely monitored treatment interruptions. Although his HIV remained in remission longer than expected - for three and eight months - eventually, the virus returned, showing that the process of stem cell transplantation itself is not enough to eradicate HIV. More recently, the researchers reported that a bone marrow transplant recipient in Minnesota had viral remission lasting almost 10 months after an interruption of the analytical treatment, but he also ended up experiencing viral recovery.
The so-called London patient, who remains anonymouswho remains anonymous, underwent stem cell transplantation to treat Hodgkin's lymphoma in May of 2016. Like Brown, his donor had a double mutation CCR5-delta-32.
The man continued his regimen of antiretroviral dolutegravir (Tivicay), ril
Transplantation led to complete remission of lymphoma and the tests showed that CD4 T cells from man now lack CCR5 receptors. Extensive tests of blood plasma and T cells revealed undetectable HIV and their level of HIV-specific antibodies also decreased. About 10 weeks after transplantation, he developed a mild graft-versus-host disease, which resolved on his own. He also experienced the reactivation of pre-existing Epstein-B (EBV) and cytomegalovirus (CMV), which were treated.
The man stopped antiretroviral therapy on an interruption of 17 analytical treatment months after transplantation. Its viral load in the blood remains undetectable 18 months later, no HIV DNA can be found in peripheral CD4 cells using a sensitive test with a limit of 1 copy / ml and tests have not shown “reactive” viruses on 24 million resting T cells. A blood sample revealed pieces of viral genetic material, which may reflect laboratory contamination or defective virus that is unable to replicate. Unlike Brown, the London patient has not yet been tested for residual HIV in his gut and other tissues.
These findings demonstrate that "the Berlin patient was not an anomaly," the researchers said. Moreover, this current case shows that remission can happen without chemotherapy or severe conditioning radiation.
Although this appears to be the second longest remission of adult HIV still observed, they recognize that "it is premature to conclude that this patient has been cured."
A poster presented at the CROI described another case of long-term HIV remission following a transplant of stem cells from oneowith a double mutation CCR5-delta-32. This patient, treated in Dusseldorf, was submitted to the February 2013 procedure for the treatment of leukemia myeloid acute The man remained on antiretroviral therapy with undetectable viral load until November of 2018. Extensive tests did not show viral DNA in their bone marrow, samples of intestinal tissue samples from rectal tissue or lymph nodes. The Düsseldorf patient stopped antiretroviral therapy in November of 2018, still has HIV undetectable and is being monitored continuously
Experts warn that even if CCR5-delta-32 stem cell transplantation can lead to a functional cure for HIV, this high risk procedure will not be an option for most people. Life-threatening stem cell transplant - Brown almost died during the process and was left with long lasting side effects. However, this new case increases the evidence that the use of gene therapy to exclude CCR5 receptors from T cells may be a viable approach.
"This is not an appropriate treatment for people with HIV who do not have cancer," the Treatment Action Group said in a statement. "The hope is that lessons can be learned to help develop more widely applicable therapeutic approaches to achieving remissions or cures for HIV."
Gupta RK et al. Sustained remission of HIV-1 after HSCT allogeneic CCR5 delt32 homozygous. Conference
Gupta RK et al. Remission of HIV-1 after transplantation of hematopoietic stem cells CCr532 / Δ32. Nature, 2019.
Jensen BO et al. Interruption of analytical treatment (ITA) after HSCT CCR-D32 allogeneic to LMA in 2013. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 394 LB, 2019