Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study
Por:
Salgado, M, Gálvez, C, Nijhuis, M, Kwon, M, Cardozo-Ojeda, EF, Badiola, J, Gorman, MJ, Huyveneers, LEP, Urrea, V, Bandera, A, Jensen, BEO, Vandekerckhove, L, Jurado, M, Raj, K, Wiesch, JSZ, Bailen, R, Eberhard, JM, Nabergoj, M, Hütter, G, Saldaña-Moreno, R, Oldford, S, Barrett, L, Ramirez, MLM, Garba, S, Gupta, RK, Revollo, B, Ferra-Coll, C, Kuball, J, Alter, G, Sáez-Cirión, A, Diez-Martin, JL, Duke, ER, Schiffer, JT, Wensing, A and Martinez-Picado, J
Publicada:
1 jun 2024
Ahead of Print:
1 may 2024
Resumen:
Background Allogeneic haematopoietic stem -cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. Methods In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5 Delta 32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV -specific antibodies were measured in plasma. We used the Wilcoxon signed -rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann -Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. Findings We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV -DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV -specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 15 months). Interpretation Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T -cell immune responses might be a more reliable marker than antibody decline after allo-HSCT.
Filiaciones:
:
IrsiCaixa, Badalona 08916, Spain
Germans Trias & Pujol Res Inst, Badalona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas, Madrid, Spain
Gálvez, C:
IrsiCaixa, Badalona 08916, Spain
Nijhuis, M:
Univ Med Ctr Utrecht, Dept Med Microbiol, Translat Virol, Utrecht, Netherlands
Univ Witwatersrand, HIV Pathogenesis Res Unit, Johannesburg, South Africa
Kwon, M:
Hosp Univ Gregorio Maranon, Inst Hlth Res Gregorio Maranon, Dept Hematol, Madrid, Spain
Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Cardozo-Ojeda, EF:
Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA
Xencor, Pasadena, CA USA
Badiola, J:
Univ Hosp Virgen de las Nieves, Granada, Spain
Gorman, MJ:
Ragon Inst Mass Gen MIT & Harvard, Cambridge, MA USA
Moderna Therapeut, Cambridge, MA USA
Huyveneers, LEP:
Univ Med Ctr Utrecht, Dept Med Microbiol, Translat Virol, Utrecht, Netherlands
:
IrsiCaixa, Badalona 08916, Spain
Bandera, A:
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Infect Dis Unit, Milan, Italy
Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy
Jensen, BEO:
Heinrich Heine Univ, Dept Gastroenterol Hepatol & Infect Dis, Med Fac, Dusseldorf, Germany
Heinrich Heine Univ, Univ Hosp Dusseldorf, Dusseldorf, Germany
Vandekerckhove, L:
Univ Ghent, Ghent Univ Hosp, Dept Internal Med & Pediat, HIV Cure Res Ctr, Ghent, Belgium
Jurado, M:
Univ Hosp Virgen de las Nieves, Granada, Spain
Raj, K:
Kings Coll Hosp London, London, England
Wiesch, JSZ:
Univ Med Ctr Hamburg Eppendorf, Dept Med, Infect Dis Unit, Hamburg, Germany
German Ctr Infect Res, Partner Site Hamburg Lubeck Borstel Riems, Hamburg, Germany
Bailen, R:
Hosp Univ Gregorio Maranon, Inst Hlth Res Gregorio Maranon, Dept Hematol, Madrid, Spain
Eberhard, JM:
Univ Med Ctr Hamburg Eppendorf, Dept Med, Infect Dis Unit, Hamburg, Germany
German Ctr Infect Res, Partner Site Hamburg Lubeck Borstel Riems, Hamburg, Germany
Helmholtz Inst One Hlth, Greifswald, Germany
Nabergoj, M:
Hop Univ Geneve, Div Hematol, Geneva, Switzerland
Inst Cent Hop, Hematol Serv, Sion, Switzerland
Hütter, G:
DKMS Collect Ctr, Dresden, Germany
Saldaña-Moreno, R:
Hosp Gen Jerez de la Frontera, Cadiz, Spain
Oldford, S:
Dalhousie Univ, Nova Scotia Hlth, Halifax, NS, Canada
Barrett, L:
Dalhousie Univ, Nova Scotia Hlth, Halifax, NS, Canada
Ramirez, MLM:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas, Madrid, Spain
Univ Hosp La Paz, IdiPAZ, Madrid, Spain
Garba, S:
Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA
Merck, Rahway, NJ USA
Gupta, RK:
Univ Cambridge, Dept Med, Cambridge, England
Revollo, B:
Univ Hosp Germans Trias I Pujol, Inst Catala Oncol, Dept Infect Dis, Badalona, Spain
:
Univ Hosp Germans Trias I Pujol, Inst Catala Oncol, Dept Hematol, Badalona, Spain
Univ Vic, Cent Univ Catalonia, Catalonia, Vic, Spain
Kuball, J:
Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands
Univ Med Ctr Utrecht, Ctr Translat Immunol, Utrecht, Netherlands
Alter, G:
Ragon Inst Mass Gen MIT & Harvard, Cambridge, MA USA
Moderna Therapeut, Cambridge, MA USA
Sáez-Cirión, A:
Univ Paris Cite, Inst Pasteur, Viral Reservoirs & Immune Control Unit, Paris, France
Diez-Martin, JL:
Hosp Univ Gregorio Maranon, Inst Hlth Res Gregorio Maranon, Dept Hematol, Madrid, Spain
Duke, ER:
Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA
Univ Washington, Dept Med, Allergy & Infect Dis Div, Seattle, WA USA
Schiffer, JT:
Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA
Fred Hutchinson Canc Ctr, Clin Res Div, Seattle, WA USA
Univ Washington, Dept Med, Allergy & Infect Dis Div, Seattle, WA USA
Wensing, A:
Univ Med Ctr Utrecht, Dept Med Microbiol, Translat Virol, Utrecht, Netherlands
Univ Witwatersrand, Fac Hlth Sci, Ezintsha, Johannesburg, South Africa
:
IrsiCaixa, Badalona 08916, Spain
Germans Trias & Pujol Res Inst, Badalona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas, Madrid, Spain
Univ Vic, Cent Univ Catalonia, Catalonia, Vic, Spain
Catalan Inst Res & Adv Studies, Barcelona, Spain
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