Achievement of full donor chimerism with episodes of alloreactivity contributes to reduce the HIV reservoir after allogeneic stem cell transplantation
Supplement : Abstracts of the IAS HIV Cure and Cancer Forum 2017Journal of Virus Eradication 2017; 3 supplement 1
Abstract No : OA5-1
M. Salgado1, M. Kwon2, C. Gálvez1, M. Nijhuis3, J. Schulze zur Wiesch4, A. Bandera5, E. Knops6, J. Badiola7, B. Jensen8, A. Saez-Cirión9, M. Jurado7, Rolf Kaiser8, G. Hutter10, V. Rocha11, G. Kobbe12, A. Wensing3, J.L. Diez2, J. Martinez-Picado1
1AIDS Research Institute, IrsiCaixa,Badalona,Spain, 2Hospital Gregorio Marañón,Madrid,Spain, 3University Medical Center Utrecht,Utrecht,Netherlands, 4University Medical Center Hamburg-Eppendorf,Hamburg,Germany, 5San Gerardo Hospital, University of Milano-Bicocca,Monza,Italy, 6Institut für Virologie,Köln,Germany, 7University Hospital Virgen de las Nieves,Granada,Spain, 8Department for Gastroenterology, Hepatology and Infectious Diseases, Universitätsklinikum Düsseldorf,Germany, 9Pasteur Institute,Paris,France, 10Cellex,Dresden,Germany, 11Churchill Hospital, Oxford University,UK, 12Department of Haematology, Oncology and Clinical Immunology, Universitätsklinikum Düsseldorf,Germany
To date, the only evidence of a medical intervention that has been able to cure HIV-1 infection (the ‘Berlin patient’), involved an allogeneic stem cell transplantation (SCT) from a donor who was homozygous for CCR5Δ32. The multifactorial mechanisms that led to such unique outcome are not clear yet, mainly due to the scarce number of HIV+ transplanted subjects that have been reported. The IciStem Consortium has compiled the first cohort of HIV+ individuals that have gone through an allogeneic SCT with a comprehensive clinical, virological and immunological follow up.
The IciStem Cohort includes 23 HIV+ transplanted subjects under cART. Analysis of the HIV-1 reservoir was performed pre- and post-transplantation by using qVOA from CD4+ T cells obtained from leukapheresis. HIV-DNA was also measured by ddPCR in CD4+ T cells from peripheral blood, ileum, and bone marrow. SCA was performed in plasma and CSF. Chimerism was performed by short tandem repeat PCR (STR-PCR).
Twenty-three HIV+ subjects have been followed within the IciStem Cohort: 17 transplanted with CCR5wt donor's cells and 6 with CCR5Δ32/Δ32 donor's cells. Twenty transplants involved bone marrow, and 3 involved cord blood units. The most prevalent disease was lymphoma (48%), followed by acute leukemia (30%), and myelodysplastic syndrome (9%). All the individuals experienced a decrease of HIV viral reservoir, mainly measured as HIV-RNA in plasma, and cell-associated HIV-DNA in CD4+ T cells. Up to date, 7 subjects are beyond the second year post-transplantation and clinically stable: 6/7 are undetectable for qVOA, HIV-DNA in blood, ileum and bone marrow, and ultrasensitive HIV-RNA in plasma and CSF. The detectable individual is the only one that did not reach full chimera measured by ultrasensitive chimerism. All subjects with undetectable HIV reservoir experienced mild graft versus host immune responses during the first months after transplantation.
The allogeneic stem cell transplantation is the only clinical intervention that has shown a dramatic reduction of the HIV reservoir in antiretroviral treated subjects. It seems that the achievement of full donor chimerism with episodes of alloreactivity that can lead to graft vs. HIV response might contribute to major reductions on the HIV reservoir during cART.