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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Original publication

DOI

10.1093/cid/civ219

Type

Journal article

Journal

Clin Infect Dis

Publication Date

01/07/2015

Volume

61

Pages

120 - 128

Keywords

CD8, HIV, cure, elite control, myeloablation, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Enzyme-Linked Immunospot Assay, HIV Antibodies, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Melphalan, Middle Aged, Models, Theoretical, Multiple Myeloma, Myeloablative Agonists, Stem Cell Transplantation, T-Lymphocyte Subsets, Transplantation, Autologous, Virus Activation