Mary Wilson
Well-known member
Published 20 February 2023
DOI https://doi.org/10.1038/s41591-023-02213-x
Björn-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Lübke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Gálvez, Christiane Mummert, Caroline Passaes, Johanna M. Eberhard, Carsten Münk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gábor A. Dunay, Florian Klein, Dieter Häussinger, Johannes C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Sáez-Cirión, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado & Guido Kobbe
Abstract
Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
https://www.nature.com/articles/s41591-023-02213-x
DOI https://doi.org/10.1038/s41591-023-02213-x
Björn-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Lübke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Gálvez, Christiane Mummert, Caroline Passaes, Johanna M. Eberhard, Carsten Münk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gábor A. Dunay, Florian Klein, Dieter Häussinger, Johannes C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Sáez-Cirión, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado & Guido Kobbe
Abstract
Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
https://www.nature.com/articles/s41591-023-02213-x