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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• 作者：Damalie Nakanjako (1) (2)
  Isaac Ssewanyana (3)
  Harriet Mayanja-Kizza (1)
  Agnes Kiragga (2)
  Robert Colebunders (5) (6)
  Yukari C Manabe (2)
  Rose Nabatanzi (3)
  Moses R Kamya (1)
  Huyen Cao (4)
  
• 刊名：BMC Infectious Diseases
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：11
• 期：1
• 全文大小：1136KB
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  38. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/11/43/prepub
  
• 作者单位：Damalie Nakanjako (1) (2)
  Isaac Ssewanyana (3)
  Harriet Mayanja-Kizza (1)
  Agnes Kiragga (2)
  Robert Colebunders (5) (6)
  Yukari C Manabe (2)
  Rose Nabatanzi (3)
  Moses R Kamya (1)
  Huyen Cao (4)
  
  1. Department of Medicine, Makerere University School of Medicine, Kampala, Uganda
  2. Infectious Diseases Institute, Makerere University School of Medicine, Kampala, Uganda
  3. Joint Clinical Research Center, Kampala, Uganda
  5. Department of Clinical sciences, HIV/STD Unit, Institute of Tropical Medicine, Antwerp, Belgium
  6. Department of Epidemiology and Social Sciences, University of Antwerp, Antwerp, Belgium
  4. California Department of Public Health, 94804, Richmond, California, USA
  

文摘

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.