Dataset Information

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

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.

SUBMITTER: Smith NM

PROVIDER: S-EPMC4463006 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Smith Nicola M G NM Mlcochova Petra P Watters Sarah A SA Aasa-Chapman Marlene M I MM Rabin Neil N Moore Sally S Edwards Simon G SG Garson Jeremy A JA Grant Paul R PR Ferns R Bridget RB Kashuba Angela A Mayor Neema P NP Schellekens Jennifer J Marsh Steven G E SG McMichael Andrew J AJ Perelson Alan S AS Pillay Deenan D Goonetilleke Nilu N Gupta Ravindra K RK

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20150316 1

<h4>Background</h4>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.<h4>Methods</h4>We present observations from a HIV-1 elite controller, not treat ...[more]

PMID: 25778749

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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