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High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort

BACKGROUND: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohort...

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Autores principales: Nakanjako, Damalie, Ssewanyana, Isaac, Mayanja-Kizza, Harriet, Kiragga, Agnes, Colebunders , Robert, Manabe, Yukari C, Nabatanzi , Rose, Kamya, Moses R, Cao, Huyen
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065409/
https://www.ncbi.nlm.nih.gov/pubmed/21299909
http://dx.doi.org/10.1186/1471-2334-11-43
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author Nakanjako, Damalie
Ssewanyana, Isaac
Mayanja-Kizza, Harriet
Kiragga, Agnes
Colebunders , Robert
Manabe, Yukari C
Nabatanzi , Rose
Kamya, Moses R
Cao, Huyen
author_facet Nakanjako, Damalie
Ssewanyana, Isaac
Mayanja-Kizza, Harriet
Kiragga, Agnes
Colebunders , Robert
Manabe, Yukari C
Nabatanzi , Rose
Kamya, Moses R
Cao, Huyen
author_sort Nakanjako, Damalie
collection PubMed
description BACKGROUND: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. METHODS: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. RESULTS: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. CONCLUSION: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
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spelling pubmed-30654092011-03-29 High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort Nakanjako, Damalie Ssewanyana, Isaac Mayanja-Kizza, Harriet Kiragga, Agnes Colebunders , Robert Manabe, Yukari C Nabatanzi , Rose Kamya, Moses R Cao, Huyen BMC Infect Dis Research Article BACKGROUND: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. METHODS: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. RESULTS: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. CONCLUSION: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART. BioMed Central 2011-02-08 /pmc/articles/PMC3065409/ /pubmed/21299909 http://dx.doi.org/10.1186/1471-2334-11-43 Text en Copyright ©2011 Nakanjako et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nakanjako, Damalie
Ssewanyana, Isaac
Mayanja-Kizza, Harriet
Kiragga, Agnes
Colebunders , Robert
Manabe, Yukari C
Nabatanzi , Rose
Kamya, Moses R
Cao, Huyen
High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title_full High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title_fullStr High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title_full_unstemmed High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title_short High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
title_sort high t-cell immune activation and immune exhaustion among individuals with suboptimal cd4 recovery after 4 years of antiretroviral therapy in an african cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065409/
https://www.ncbi.nlm.nih.gov/pubmed/21299909
http://dx.doi.org/10.1186/1471-2334-11-43
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