HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial

Objectives Immune factors determining clinical progression following HIV-1 infection remain unclear. The SPARTAC trial randomised 366 participants in primary HIV infection (PHI) to different short course therapies. The aim of this study was to investigate how early immune responses in PHI impacted c...

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मुख्य लेखकों: Frater, A, Ewings, F, Hurst, J, Brown, H, Robinson, N, Fidler, S, Babiker, A, Weber, J, Porter, K, Phillips, R
स्वरूप: Journal article
भाषा:English
प्रकाशित: Wolters Kluwer 2013
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author Frater, A
Ewings, F
Hurst, J
Brown, H
Robinson, N
Fidler, S
Babiker, A
Weber, J
Porter, K
Phillips, R
author_facet Frater, A
Ewings, F
Hurst, J
Brown, H
Robinson, N
Fidler, S
Babiker, A
Weber, J
Porter, K
Phillips, R
author_sort Frater, A
collection OXFORD
description Objectives Immune factors determining clinical progression following HIV-1 infection remain unclear. The SPARTAC trial randomised 366 participants in primary HIV infection (PHI) to different short course therapies. The aim of this study was to investigate how early immune responses in PHI impacted clinical progression in SPARTAC. Design and Methods Participants with PHI recruited to the SPARTAC trial were sampled at enrolment, prior to commencing any therapy. HIV-1 specific CD4 and CD8 ELISpot responses were measured by gamma interferon ELISPOT. Immunological data were associated with baseline covariates and times to clinical progression using logistic regression, Kaplan-Meier plots, and Cox models. Results Making a CD4 T cell ELISpot response (n=119) at enrolment was associated with higher CD4 counts (p=0.02) and to some extent lower plasma HIV RNA (p=0.07). There was no correlation between the number of overlapping Gag CD8 T cell ELISpot responses (n=138) and plasma HIV-1 RNA viral load. Over a median follow-up of 2.9 years, baseline CD4 cell ELISpot responses (n=119) were associated with slower clinical progression (p=0.01; log-rank). Over a median of 3.1 years, there was no evidence for a survival advantage imposed by CD8 T cell immunity (p=0.82). Conclusions These data support a dominant protective role for CD4 T cell immunity in PHI compared with CD8 T cell responses, and are highly pertinent to HIV pathogenesis and vaccines, indicating that vaccine-induced CD4 responses may confer sustained benefit.
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spelling oxford-uuid:7d8c6e16-c850-46f4-871b-53e64b0640022022-03-26T21:04:32ZHIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC TrialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7d8c6e16-c850-46f4-871b-53e64b064002EnglishSymplectic Elements at OxfordWolters Kluwer2013Frater, AEwings, FHurst, JBrown, HRobinson, NFidler, SBabiker, AWeber, JPorter, KPhillips, RObjectives Immune factors determining clinical progression following HIV-1 infection remain unclear. The SPARTAC trial randomised 366 participants in primary HIV infection (PHI) to different short course therapies. The aim of this study was to investigate how early immune responses in PHI impacted clinical progression in SPARTAC. Design and Methods Participants with PHI recruited to the SPARTAC trial were sampled at enrolment, prior to commencing any therapy. HIV-1 specific CD4 and CD8 ELISpot responses were measured by gamma interferon ELISPOT. Immunological data were associated with baseline covariates and times to clinical progression using logistic regression, Kaplan-Meier plots, and Cox models. Results Making a CD4 T cell ELISpot response (n=119) at enrolment was associated with higher CD4 counts (p=0.02) and to some extent lower plasma HIV RNA (p=0.07). There was no correlation between the number of overlapping Gag CD8 T cell ELISpot responses (n=138) and plasma HIV-1 RNA viral load. Over a median follow-up of 2.9 years, baseline CD4 cell ELISpot responses (n=119) were associated with slower clinical progression (p=0.01; log-rank). Over a median of 3.1 years, there was no evidence for a survival advantage imposed by CD8 T cell immunity (p=0.82). Conclusions These data support a dominant protective role for CD4 T cell immunity in PHI compared with CD8 T cell responses, and are highly pertinent to HIV pathogenesis and vaccines, indicating that vaccine-induced CD4 responses may confer sustained benefit.
spellingShingle Frater, A
Ewings, F
Hurst, J
Brown, H
Robinson, N
Fidler, S
Babiker, A
Weber, J
Porter, K
Phillips, R
HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title_full HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title_fullStr HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title_full_unstemmed HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title_short HIV-1 Specific CD4 Responses in Primary HIV-1 Infection predict disease progression in the SPARTAC Trial
title_sort hiv 1 specific cd4 responses in primary hiv 1 infection predict disease progression in the spartac trial
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