Imperial College London
Alternate

DrNesrinaImami

Faculty of Medicine, Department of Infectious Disease

Reader in Immunology
 
 
 
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Contact

 

+44 (0)20 3315 5987n.imami Website

 
 
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Location

 

I.2.8Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Herasimtschuk:2014:10.1016/j.vaccine.2014.09.072,
author = {Herasimtschuk, A and Downey, J and Nelson, M and Moyle, G and Mandalia, S and Sikut, R and Adojaan, M and Stanescu, I and Gotch, F and Imami, N},
doi = {10.1016/j.vaccine.2014.09.072},
journal = {VACCINE},
pages = {7005--7013},
title = {Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection},
url = {http://dx.doi.org/10.1016/j.vaccine.2014.09.072},
volume = {32},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundThis randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.MethodsTwelve HIV-1+ patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm3 blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n = 3); (2) vaccine alone (n = 4); or (3) IL-2, GM-CSF and rhGH (n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.ResultsMedian baseline CD4 T-cell count was 757 cells/mm3 (interquartile range [IQR] 567–886 cells/mm3), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p = 0.0083) and improved CD4/CD8 T-cell ratios (p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p = 0.0122) and elevated IFN-γ production in response to Tat (p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.ConclusionsMultifarious immunotherapeutic approaches in the context of fully s
AU  - Herasimtschuk,A
AU  - Downey,J
AU  - Nelson,M
AU  - Moyle,G
AU  - Mandalia,S
AU  - Sikut,R
AU  - Adojaan,M
AU  - Stanescu,I
AU  - Gotch,F
AU  - Imami,N
DO  - 10.1016/j.vaccine.2014.09.072
EP  - 7013
PY  - 2014///
SN  - 0264-410X
SP  - 7005
TI  - Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection
T2  - VACCINE
UR  - http://dx.doi.org/10.1016/j.vaccine.2014.09.072
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000346222000019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/61508
VL  - 32
ER  -
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