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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
BMC Infectious Diseases, Volume 11, Article 43, Year 2011
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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. © 2011 Nakanjako et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Nakanjako, Damalie
Uganda, Kampala
School of Medicine, Makerere University College of Health Sciences
Ssewanyana, Isaac
Uganda, Kampala
Joint Clinical Research Center Uganda
Mayanja-Kizza, Harriet
Uganda, Kampala
School of Medicine, Makerere University College of Health Sciences
Kiragga, Agnes N.
Uganda, Kampala
School of Medicine, Makerere University College of Health Sciences
Colebunders, Robert Leon
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Belgium, Antwerpen
Universiteit Antwerpen
Manabe, Yukari C.
Uganda, Kampala
School of Medicine, Makerere University College of Health Sciences
Nabatanzi, Rose
Uganda, Kampala
Joint Clinical Research Center Uganda
Kamya, Moses Robert K.
Uganda, Kampala
School of Medicine, Makerere University College of Health Sciences
Cao, Huyen L.
United States, Richmond
California Department of Public Health
Statistics
Citations: 111
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1186/1471-2334-11-43
e-ISSN:
14712334
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cohort Study