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 2017

Journal of Virus Eradication 2017; 3 supplement 1

Abstract No : OA5-1

Author(s):

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

Abstract :

Background

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.

Methods

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).

Results

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.

Conclusions

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.