The conditioning regimen used as part of the Berlin patient’s hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus–infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4+ and CD8+ T cells and CD20+ B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs. The disrupted T cell homeostasis and markers of microbial translocation positively correlated with an increased viral rebound after cART interruption. Quantitative viral outgrowth and Tat/rev–induced limiting dilution assays showed that the size of the latent SHIV reservoir did not correlate with viral rebound. These findings identify perturbations of the immune system as a mechanism for the failure of autologous transplantation to eradicate HIV. Thus, transplantation strategies may be improved by incorporating immune modulators to prevent disrupted homeostasis, and gene therapy to protect transplanted cells.
Christopher W. Peterson, Clarisse Benne, Patricia Polacino, Jasbir Kaur, Cristina E. McAllister, Abdelali Filali-Mouhim, Willi Obenza, Tiffany A. Pecor, Meei-Li Huang, Audrey Baldessari, Robert D. Murnane, Ann E. Woolfrey, Keith R. Jerome, Shiu-Lok Hu, Nichole R. Klatt, Stephen DeRosa, Rafick P. Sékaly, Hans-Peter Kiem
Title and authors | Publication | Year |
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Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?
Harper J, Betts MR, Lichterfeld M, Müller-Trutwin M, Margolis D, Bar KJ, Li JZ, McCune JM, Lewin SR, Kulpa D, Diallo DD, Lederman MM, Paiardini M |
Pathogens and Immunity | 2024 |
Erratum to: Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?
Harper J, Betts MR, Lichterfeld M, Müller-Trutwin M, Margolis D, Bar KJ, Li JZ, McCune JM, Lewin SR, Kulpa D, Ávila-Ríos S, Diallo DD, Lederman MM, Paiardini M |
Pathogens & immunity | 2024 |
CD20 CAR T cells safely and reversibly ablate B cell follicles in a non-human primate model of HIV persistence.
Bui JK, Starke CE, Poole NH, Rust BJ, Jerome KR, Kiem HP, Peterson CW |
Molecular Therapy | 2024 |
Stem cell-derived CAR T cells show greater persistence, trafficking, and viral control compared to ex vivo transduced CAR T cells
Carrillo MA, Zhen A, Mu W, Rezek V, Martin H, Peterson CW, Kiem HP, Kitchen SG |
Molecular Therapy | 2024 |
Efficient ex vivo expansion of conserved element vaccine-specific CD8+ T-cells from SHIV-infected, ART-suppressed nonhuman primates
Dross S, Venkataraman R, Patel S, Huang ML, Bollard CM, Rosati M, Pavlakis GN, Felber BK, Bar KJ, Shaw GM, Jerome KR, Mullins JI, Kiem HP, Fuller DH, Peterson CW |
Frontiers in immunology | 2023 |
Efficient manufacturing and engraftment of CCR5 gene-edited HSPCs following busulfan conditioning in nonhuman primates
Murray J, Einhaus T, Venkataraman R, Radtke S, Zhen A, Carrillo MA, Kitchen SG, Peterson CW, Kiem HP |
2023 | |
Strategies for enhancing CAR T cell expansion and persistence in HIV infection
Rothemejer FH, Lauritsen NP, Søgaard OS, Tolstrup M |
Frontiers in immunology | 2023 |
Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected anti-retroviral therapy-suppressed macaques
Wu HL, Busman-Sahay K, Weber WC, Waytashek CM, Boyle CD, Bateman KB, Reed JS, Hwang JM, Shriver-Munsch C, Swanson T, Northrup M, Armantrout K, Price H, Robertson-LeVay M, Uttke S, Kumar MR, Fray EJ, Taylor-Brill S, Bondoc S, Agnor R, Junell SL, Legasse AW, Moats C, Bochart RM, Sciurba J, Bimber BN, Sullivan MN, Dozier B, MacAllister RP, Hobbs TR, Martin LD, Panoskaltsis-Mortari A, Colgin LM, Siliciano RF, Siliciano JD, Estes JD, Smedley JV, Axthelm MK, Meyers G, Maziarz RT, Burwitz BJ, Stanton JJ, Sacha JB |
Immunity | 2023 |
Stem cell-derived CAR-T cells traffic to HIV reservoirs in macaques
Isaac M. Barber-Axthelm, Valerie Barber-Axthelm, Kai Yin Sze, Anjie Zhen, Gajendra Suryawanshi, Irvin S. Chen, Jerome A. Zack, Scott Kitchen, Hans-Peter Kiem, Christopher W. Peterson |
JCI Insight | 2021 |
Genome editing in large animal models
LH Maynard, O Humbert, CW Peterson, HP Kiem |
Molecular Therapy | 2021 |
Thresholds for post-rebound SHIV control after CCR5 gene-edited autologous hematopoietic cell transplantation
EF Cardozo-Ojeda, ER Duke, CW Peterson, DB Reeves, BT Mayer, HP Kiem, JT Schiffer |
eLife | 2021 |
Robust expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates
BJ Rust, LS Kean, L Colonna, KE Brandenstein, NH Poole, W Obenza, MR Enstrom, CR Maldini, GI Ellis, CM Fennessey, ML Huang, BF Keele, KR Jerome, JL Riley, HP Kiem, CW Peterson |
Blood | 2020 |
The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
GW Suryawanshi, W Khamaikawin, J Wen, S Shimizu, H Arokium, Y Xie, E Wang, S Kim, H Choi, C Zhang, H Yu, AP Presson, N Kim, DS An, IS Chen, S Kim |
Science Advances | 2020 |
Autologous, Gene-Modified Hematopoietic Stem and Progenitor Cells Repopulate the Central Nervous System with Distinct Clonal Variants
CW Peterson, JE Adair, ME Wohlfahrt, C Deleage, S Radtke, B Rust, KK Norman, ZK Norgaard, LE Schefter, GM Sghia-Hughes, A Repetto, A Baldessari, RD Murnane, JD Estes, HP Kiem |
Stem Cell Reports | 2019 |
Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy
CW Peterson, J Wang, C Deleage, S Reddy, J Kaur, P Polacino, A Reik, ML Huang, KR Jerome, SL Hu, MC Holmes, JD Estes, HP Kiem, G Silvestri |
PLoS pathogens | 2018 |
Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
L Colonna, CW Peterson, JB Schell, JM Carlson, V Tkachev, M Brown, A Yu, S Reddy, WM Obenza, V Nelson, PS Polacino, H Mack, SL Hu, K Zeleski, M Hoffman, J Olvera, SN Furlan, H Zheng, A Taraseviciute, DJ Hunt, K Betz, JF Lane, K Vogel, CE Hotchkiss, C Moats, A Baldessari, RD Murnane, C English, CA Astley, S Wangari, B Agricola, J Ahrens, N Iwayama, A May, L Stensland, ML Huang, KR Jerome, HP Kiem, LS Kean |
Nature Communications | 2018 |
Long-Term Persistence of Anti-HIV Broadly Neutralizing Antibody-Secreting Hematopoietic Cells in Humanized Mice
AS Kuhlmann, KG Haworth, IM Barber-Axthelm, C Ironside, MA Giese, CW Peterson, HP Kiem |
Molecular Therapy | 2018 |
Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS
A Zhen, CW Peterson, MA Carrillo, SS Reddy, CS Youn, BB Lam, NY Chang, HA Martin, JW Rick, J Kim, NC Neel, VK Rezek, M Kamata, IS Chen, JA Zack, HP Kiem, SG Kitchen, RC Desrosiers |
PLoS pathogens | 2017 |
Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia
DB Reeves, CW Peterson, HP Kiem, JT Schiffer, G Silvestri |
Journal of virology | 2017 |