CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy

Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8+ T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths,...

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Main Authors: Jennifer Serwanga, Susan Mugaba, Auma Betty, Edward Pimego, Sarah Walker, Paula Munderi, Charles Gilks, Frances Gotch, Heiner Grosskurth, Pontiano Kaleebu
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:AIDS Research and Treatment
Online Access:http://dx.doi.org/10.1155/2011/875028
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author Jennifer Serwanga
Susan Mugaba
Auma Betty
Edward Pimego
Sarah Walker
Paula Munderi
Charles Gilks
Frances Gotch
Heiner Grosskurth
Pontiano Kaleebu
author_facet Jennifer Serwanga
Susan Mugaba
Auma Betty
Edward Pimego
Sarah Walker
Paula Munderi
Charles Gilks
Frances Gotch
Heiner Grosskurth
Pontiano Kaleebu
author_sort Jennifer Serwanga
collection DOAJ
description Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8+ T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n=42) and continuous treatment (CT) (n=46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants. Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8+IFNγ+ and CD8+Perforin+ responses. However, STI was associated with significant decline in breadth of bi-functional (CD8+IFNγ+Perforin+) responses; P=.02, Mann-Whitney test. Conclusions. STI in individuals initiated onto ART at <200 CD4+ T-cell counts/μl significantly reduced occurrence of bifunctional CD8+IFNγ+/Perforin+ responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.
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institution Kabale University
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spelling doaj-art-c1a6d59df54e466aba9361f3346494182025-02-03T01:07:00ZengWileyAIDS Research and Treatment2090-12402090-12592011-01-01201110.1155/2011/875028875028CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI SubstudyJennifer Serwanga0Susan Mugaba1Auma Betty2Edward Pimego3Sarah Walker4Paula Munderi5Charles Gilks6Frances Gotch7Heiner Grosskurth8Pontiano Kaleebu9MRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaMRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UKMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaImperial College London, South Kensington Campus, London SW7 2AZ, UKDepartment of Immunology, Imperial College, Chelsea and Westminster Hospital, London SW10 9NH, UKMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaMRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, UgandaObjective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8+ T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n=42) and continuous treatment (CT) (n=46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants. Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8+IFNγ+ and CD8+Perforin+ responses. However, STI was associated with significant decline in breadth of bi-functional (CD8+IFNγ+Perforin+) responses; P=.02, Mann-Whitney test. Conclusions. STI in individuals initiated onto ART at <200 CD4+ T-cell counts/μl significantly reduced occurrence of bifunctional CD8+IFNγ+/Perforin+ responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.http://dx.doi.org/10.1155/2011/875028
spellingShingle Jennifer Serwanga
Susan Mugaba
Auma Betty
Edward Pimego
Sarah Walker
Paula Munderi
Charles Gilks
Frances Gotch
Heiner Grosskurth
Pontiano Kaleebu
CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
AIDS Research and Treatment
title CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
title_full CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
title_fullStr CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
title_full_unstemmed CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
title_short CD8+ T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+ T Cells <200 Cell/μL: The DART Trial STI Substudy
title_sort cd8 t cell responses before and after structured treatment interruption in ugandan adults who initiated art with cd4 t cells 200 cell μl the dart trial sti substudy
url http://dx.doi.org/10.1155/2011/875028
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