Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.

Autor: Varco-Merth B; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Chaunzwa M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Duell DM; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Marenco A; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Goodwin W; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Dannay R; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Nekorchuk M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Shao D; Fred Hutchinson Cancer Research Center, Seattle, Washington State, United States of America., Busman-Sahay K; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Fennessey CM; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Silipino L; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Hull M; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Bosche WJ; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Fast R; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Oswald K; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Shoemaker R; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Bochart R; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., MacAllister R; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Labriola CS; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Smedley JV; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Axthelm MK; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Davenport MP; Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia., Edlefsen PT; Fred Hutchinson Cancer Research Center, Seattle, Washington State, United States of America., Estes JD; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Keele BF; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Lifson JD; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Lewin SR; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Victorian Infectious Diseases Service, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia., Picker LJ; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America., Okoye AA; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Aug 22; Vol. 20 (8), pp. e1012496. Date of Electronic Publication: 2024 Aug 22 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012496
Abstrakt: Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes. However, treatment was followed by proliferation and reconstitution of CD4+ T cells in blood, and despite ongoing ART, levels of cell-associated SIV DNA in blood and lymphoid tissues were not substantially different between alemtuzumab-treated and control RM after immune cell reconstitution, irrespective of the time of alemtuzumab treatment. Upon ART cessation, 19 of 22 alemtuzumab-treated RM and 13 of 13 controls rebounded with no difference in the time to rebound between treatment groups. Time to rebound and reactivation rate was associated with plasma viral loads (pVLs) at time of ART initiation, suggesting lymphocyte depletion had no durable impact on the RCVR. However, 3 alemtuzumab-treated RM that had lowest levels of pre-ART viremia, failed to rebound after ART withdrawal, in contrast to controls with similar levels of SIV replication. These observations suggest that alemtuzumab therapy has little to no ability to reduce well-established RCVRs but may facilitate RCVR destabilization when pre-ART virus levels are particularly low.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Varco-Merth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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