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http://hdl.handle.net/123456789/1355
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| 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 |
| Authors: | Nakanjako, Damalie
Ssewanyana, Isaac
Mayanja-Kizza, Harriet
Kiragga, Agnes
Colebunders, Robert
Manabe, Yukari C.
Nabatanzi, Rose
Kamya, Moses R.
Cao, Huyen |
| Keywords: | Antiretroviral therapy (ART)
HIV/AIDS
CD4 Count
T-cell immune activation
HIV Infection |
| Issue Date: | 2011 |
| Publisher: | BioMed Central |
| Citation: | Nakanjako, D., Ssewanyana, I., Mayanja-Kizza, H., Kiragga, A., Colebunders, R., Manabe, Y.C., Nabatanzi, R., Kamya, M.R., Cao, H. (2011). 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, 11(43). |
| 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/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. |
| URI: | http://www.biomedcentral.com/1471-2334/11/43
http://hdl.handle.net/123456789/1355 |
| ISSN: | 1471-2334 |
| Appears in Collections: | Research Articles (Health-Sciences)
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| nakanjako-damalie-chs-res.pdf | | 635Kb | Adobe PDF | View/Open |
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