Smith, NMG;
Mlcochova, P;
Watters, SA;
Aasa-Chapman, MMI;
Rabin, N;
Moore, S;
Edwards, SG;
... Gupta, RK; + view all
(2015)
Proof of principle for immune control of 1 global HIV1 reactivation in vivo.
Clinical Infectious Diseases
10.1093/cid/civ219.
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Abstract
Background: Emerging data relating to HIV1 cure suggest vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clear reactivated, HIV1 infected cells. However, evidence for this approach in humans is lacking and parameters required for a vaccine are unknown because opportunities to study HIV1 reactivation are rare. Methods: We present observations from a HIV1 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. ELISpot, intracellular cytokine staining and tetramer staining were performed on PBMC; in vitro CD8 T cell mediated control of virion production by autologous CD4 T cells was quantified and neutralizing antibody titres were measured. Results: Viral rebound was measured at 28,000 copies/ml on day 13 posttransplant before rapid decay to <50 copies/ml in two 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 NK cells, recovered with virus rebound. However, most striking was expansion of highly functional HIV1 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 HIV1 reactivation, remarkably with potency equivalent to cART. These data will inform design of vaccines for use in HIV1 curative interventions.
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