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Clin Infect Dis ; 61(1): 120-8, 2015 Jul 01.
Article in English | MEDLINE | ID: mdl-25778749

ABSTRACT

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.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , HIV-1/immunology , HIV-1/physiology , Virus Activation/immunology , Antibodies, Neutralizing/blood , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , Cytokines/analysis , Enzyme-Linked Immunospot Assay , HIV Antibodies/blood , HIV Infections/complications , Humans , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology , Melphalan/adverse effects , Melphalan/therapeutic use , Middle Aged , Models, Theoretical , Multiple Myeloma/drug therapy , Myeloablative Agonists/adverse effects , Myeloablative Agonists/therapeutic use , Stem Cell Transplantation/adverse effects , T-Lymphocyte Subsets/immunology , Transplantation, Autologous
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