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DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.
“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.
Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.
EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.
Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.
Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.
Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.
“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.
EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.
DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.
“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.
Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.
EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.
Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.
Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.
Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.
“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.
EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.
DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.
“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.
Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.
EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.
Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.
Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.
Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.
“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.
EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.
AT AIDS 2016
Key clinical point: It doesn’t appear to be necessary to use donor stem cells that are homozygous for the CCR5 delta32 mutation to achieve enormous sustained reductions in the viral reservoir in HIV-infected patients undergoing allogeneic stem cell transplantation for hematologic cancers.
Major finding: Two of three patients in a European series who have survived for longer than 3 years after stem-cell transplantation with undetectable or only trace HIV in their blood received donor cells lacking the rare CCR5 delta32 mutation.
Data source: EpiStem is an ongoing observational study of HIV-infected patients who undergo allogeneic stem cell transplantation for life-threatening hematologic cancers.
Disclosures: The EpiStem project is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. The presenter reported having no financial conflicts regarding her presentation.
