Format

Send to

Choose Destination
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.

Author information

1
Nuffield Department of Medicine, University of Oxford.
2
Department of Infection, Division of Infection and Immunity, University College London.
3
University College London Hospitals National Health Service (NHS) Foundation Trust.
4
Mortimer Market Centre, Central and North West London NHS Foundation Trust, United Kingdom.
5
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
6
Anthony Nolan Research Institute, Royal Free Hospital Cancer Institute, University College London, United Kingdom.
7
Los Alamos National Laboratory, New Mexico.
8
Department of Infection, Division of Infection and Immunity, University College London Africa Centre for Health and Population Sciences, University of KwaZulu Natal, South Africa.
9
Nuffield Department of Medicine, University of Oxford Department of Microbiology & Immunology, University of North Carolina at Chapel Hill.

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.

KEYWORDS:

CD8; HIV; cure; elite control; myeloablation

PMID:
25778749
PMCID:
PMC4463006
DOI:
10.1093/cid/civ219
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center