Proof-of-Principle for Immune Control of Global HIV-1 Reactivation In Vivo

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
Nicola M G SmithRavindra K Gupta

Abstract

Emerging data relating to human immunodeficiency virus type 1 (HIV-1) cure suggest that vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clearing of reactivated HIV-1-infected cells. However, evidence for this approach in humans is lacking, and parameters required for a vaccine are unknown because opportunities to study HIV-1 reactivation are rare. We present observations from a HIV-1 elite controller, not treated with combination antiretroviral therapy, who experienced viral reactivation following treatment for myeloma with melphalan and autologous stem cell transplantation. Mathematical modeling was performed using a standard viral dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining were performed on peripheral blood mononuclear cells; in vitro CD8 T-cell-mediated control of virion production by autologous CD4 T cells was quantified; and neutralizing antibody titers were measured. Viral rebound was measured at 28,000 copies/mL on day 13 post-transplant before rapid decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days. These kinetics were consistent with an expansion of cytotoxic effector cells and killing ...Continue Reading

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Citations

Mar 8, 2016·Open Forum Infectious Diseases·Kim A ReissJoel N Blankson
Dec 10, 2015·Expert Review of Vaccines·Anna-Lise Williamson, Edward P Rybicki
Mar 6, 2019·Nature·Ravindra K GuptaEduardo Olavarria
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Mar 14, 2019·Frontiers in Immunology·Joanna A WarrenNilu Goonetilleke
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Oct 7, 2020·ELife·Joanna A WarrenNilu Goonetilleke
Nov 13, 2020·EBioMedicine·Bezawit A WoldemeskelJoel N Blankson
Aug 30, 2019·Current Opinion in Systems Biology·Jessica M Conway, Ruy M Ribeiro
Jun 2, 2021·The Journal of Clinical Investigation·Jonathan Z Li, Joel N Blankson

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Methods Mentioned

BETA
Assay
leukapheresis
flow cytometry
enzyme-linked immunosorbent assay

Software Mentioned

Berkeley Madonna

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