The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation

Objectives. Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels...

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Main Authors: Brunt, S., Lee, S., D'Orsogna, L., Bundell, C., Burrows, S., Price, Patricia
Format: Journal Article
Published: Hindawi Publishing Corporation 2014
Online Access:http://hdl.handle.net/20.500.11937/6038
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author Brunt, S.
Lee, S.
D'Orsogna, L.
Bundell, C.
Burrows, S.
Price, Patricia
author_facet Brunt, S.
Lee, S.
D'Orsogna, L.
Bundell, C.
Burrows, S.
Price, Patricia
author_sort Brunt, S.
building Curtin Institutional Repository
collection Online Access
description Objectives. Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART. Design. We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14. Results. Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV and EBV-VCA peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF , EBV-VCA , and CMV antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years and verified in a second cohort. Conclusions. CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden.
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spelling curtin-20.500.11937-60382017-09-13T14:38:34Z The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation Brunt, S. Lee, S. D'Orsogna, L. Bundell, C. Burrows, S. Price, Patricia Objectives. Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART. Design. We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14. Results. Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV and EBV-VCA peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF , EBV-VCA , and CMV antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years and verified in a second cohort. Conclusions. CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden. 2014 Journal Article http://hdl.handle.net/20.500.11937/6038 10.1155/2014/947432 Hindawi Publishing Corporation restricted
spellingShingle Brunt, S.
Lee, S.
D'Orsogna, L.
Bundell, C.
Burrows, S.
Price, Patricia
The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title_full The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title_fullStr The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title_full_unstemmed The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title_short The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
title_sort use of humoral responses as a marker of cmv burden in hiv patients on art requires consideration of t-cell recovery and persistent b-cell activation
url http://hdl.handle.net/20.500.11937/6038