TY - JOUR
T1 - In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation
AU - Jensen, Björn Erik Ole
AU - Knops, Elena
AU - Cords, Leon
AU - Lübke, Nadine
AU - Salgado, Maria
AU - Busman-Sahay, Kathleen
AU - Estes, Jacob D.
AU - Huyveneers, Laura E.P.
AU - Perdomo-Celis, Federico
AU - Wittner, Melanie
AU - Gálvez, Cristina
AU - Mummert, Christiane
AU - Passaes, Caroline
AU - Eberhard, Johanna M.
AU - Münk, Carsten
AU - Hauber, Ilona
AU - Hauber, Joachim
AU - Heger, Eva
AU - De Clercq, Jozefien
AU - Vandekerckhove, Linos
AU - Bergmann, Silke
AU - Dunay, Gábor A.
AU - Klein, Florian
AU - Häussinger, Dieter
AU - Fischer, Johannes C.
AU - Nachtkamp, Kathrin
AU - Timm, Joerg
AU - Kaiser, Rolf
AU - Harrer, Thomas
AU - Luedde, Tom
AU - Nijhuis, Monique
AU - Sáez-Cirión, Asier
AU - Schulze zur Wiesch, Julian
AU - Wensing, Annemarie M.J.
AU - Martinez-Picado, Javier
AU - Kobbe, Guido
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
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U2 - 10.1038/s41591-023-02213-x
DO - 10.1038/s41591-023-02213-x
M3 - Article
C2 - 36807684
AN - SCOPUS:85148470784
SN - 1078-8956
VL - 29
SP - 583
EP - 587
JO - Nature medicine
JF - Nature medicine
IS - 3
ER -