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Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller

Authors :
Joseph W. Adelsberger
Milad Pooran
Danielle M. Rosenthal
Ven Natarajan
Susan F. Leitman
Noah V. Gavil
Siying Lin
Caryn G. Morse
David F. Stroncek
Robin L. Dewar
Stephen A. Migueles
Joseph A. Kovacs
Mark Connors
H. Clifford Lane
Tauseef Rehman
Brad T. Sherman
Cheryl Chairez
Adam Rupert
Source :
JCI insight. 4(18)
Publication Year :
2019

Abstract

BACKGROUND: HIV-infected patients with poor virologic control and multidrug-resistant virus have limited therapeutic options. The current study was undertaken to evaluate the safety, immunologic effects, and antiviral activity of peripheral lymphocytes transferred from an elite controller, whose immune system is able to control viral replication without antiretroviral medications, to an HLA-B*2705–matched progressor. METHODS: Approximately 22 billion cells were collected from an elite controller by lymphapheresis and infused within 6 hours into a recipient with a preinfusion CD4(+) T cell count of 10 cells/μL (1%) and HIV plasma viral load of 114,993 copies/mL. RESULTS: Donor cells were cleared from the recipient’s peripheral blood by day 8. A transient decrease in viral load to 58,421 (day 3) was followed by a rebound to 702,972 (day 6) before returning to baseline values by day 8. The decreased viral load was temporally associated with peak levels of donor T cells, including CD8(+) T cells that had high levels of expression of Ki67, perforin, and granzyme B. Notably, recipient CD8(+) T cells also showed increased expression of these markers, especially in HIV-specific tetramer–positive cells. CONCLUSION: These results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways. TRIAL REGISTRATION: ClinicalTrials.gov NCT00559416. FUNDING: Intramural Research Programs of the US NIH Clinical Center and the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute.

Details

ISSN :
23793708
Volume :
4
Issue :
18
Database :
OpenAIRE
Journal :
JCI insight
Accession number :
edsair.doi.dedup.....cb9fcc39e78fae4a411f7be8acd36b74