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Clin Infect Dis. 2015 Jul 1;61(1):120-8. doi: 10.1093/cid/civ219. Epub 2015 Mar 16.

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

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Nuffield Department of Medicine, University of Oxford.
Department of Infection, Division of Infection and Immunity, University College London.
University College London Hospitals National Health Service (NHS) Foundation Trust.
Mortimer Market Centre, Central and North West London NHS Foundation Trust, United Kingdom.
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
Anthony Nolan Research Institute, Royal Free Hospital Cancer Institute, University College London, United Kingdom.
Los Alamos National Laboratory, New Mexico.
Department of Infection, Division of Infection and Immunity, University College London Africa Centre for Health and Population Sciences, University of KwaZulu Natal, South Africa.
Nuffield Department of Medicine, University of Oxford Department of Microbiology & Immunology, University of North Carolina at Chapel Hill.



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 of productively infected CD4 T cells. Following transplantation, innate immune cells, including natural killer cells, recovered with virus rebound. However, most striking was the expansion of highly functional HIV-1-specific cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as virus control was regained.


These observations provide evidence that the human immune response is capable of controlling coordinated global HIV-1 reactivation, remarkably with potency equivalent to combination antiretroviral therapy. These data will inform design of vaccines for use in HIV-1 curative interventions.


CD8; HIV; cure; elite control; myeloablation

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