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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

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dc.contributor.author Nakanjako, D.
dc.contributor.author Ssewanyana, I.
dc.contributor.author Mayanja-Kizza, H.
dc.contributor.author Kiragga, A.
dc.contributor.author Colebunders, R.
dc.contributor.author Manabe, Y. C.
dc.contributor.author Nabatanzi, R.
dc.contributor.author Kamya, M. R.
dc.contributor.author Cao, H.
dc.date.accessioned 2011-02-22T15:01:44Z
dc.date.available 2011-02-22T15:01:44Z
dc.date.issued 2011
dc.identifier.issn 1471-2334
dc.identifier.doi http://dx.doi.org/10.1186/1471-2334-11-43
dc.identifier.other ITG-C5A
dc.identifier.other CLINIC
dc.identifier.other U-HIVCLI
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other Electronic
dc.identifier.other Abstract
dc.identifier.other UPD31
dc.identifier.uri http://hdl.handle.net/10390/6480
dc.description.abstract 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/mul], N=34 ], optimal [282 (200-415) cells/mul, N=64] and super-optimal [528 (416-878) cells/mul, 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. en
dc.language English en
dc.subject Viral diseases en
dc.subject HIV en
dc.subject AIDS en
dc.subject HAART en
dc.subject Antiretrovirals en
dc.subject T-cells en
dc.subject CD4 lymphocyte count en
dc.subject Immune activation en
dc.subject CD38 en
dc.subject HLA en
dc.subject Viral suppression en
dc.subject Adults en
dc.subject Uganda en
dc.subject Africa, East en
dc.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 en
dc.type Article-E en
dc.citation.issue 43 en
dc.citation.jtitle BMC Infectious Diseases en
dc.citation.volume 11 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/21299909
dc.citation.jabbreviation BMC Infect Dis en


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