title: Changes in levels of T cell subpopulations to monitor the response to antiretroviral therapy among HIV-1-infected patients during two years of HIV-1 replication suppression.
abstract: OBJECTIVE
  The aim of this study was to compare the effect of 2 y of antiretroviral therapy (ART) on the percentage of activated CD38⁺CD8⁺ T cells and human leukocyte antigen (HLA)-DR⁺CD8⁺ T cells, and the expression of the co-stimulatory molecule CD28 on CD4⁺ and CD8⁺ T cells in the peripheral blood of HIV-infected adults, and to assess the use of immune activation markers to predict the virological response to ART in a cohort of HIV-1-infected patients in the north-western part of China.
  
  
  METHODS
  We analyzed changes in the CD4⁺ T cell count, viral load, and the percentages of CD38⁺CD8⁺ T cells, HLA-DR⁺CD8⁺ T cells, CD28⁺CD4⁺ T cells, and CD28⁺CD8⁺ T cells in 48 patients with HIV diseases during 2 y of suppressive highly active antiretroviral therapy (HAART). Good virological responders (n = 20) were defined as those who had suppressed and maintained a plasma viral load below the detection limit of the assay for at least 12 months. Poor virological responders (n = 28) were defined as those with a detectable viral load at 6 and 12 months after beginning HAART.
  
  
  RESULTS
  Among the 20 good responders, baseline median levels of CD38⁺CD8⁺ T cells were elevated, but had decreased significantly at 24 months of therapy (p < 0.0001). Median levels of HLA-DR⁺CD8⁺ T cells also decreased at 24 months of therapy (p < 0.0001). Levels of expression of CD28⁺CD4⁺ T cells rose steadily to 6 months (p = 0.03), and smoothly reached levels observed among HIV-negative blood donors during the 24 months of therapy (p > 0.05). Levels of expression of CD28⁺CD8⁺ T cells increased at 24 months (p = 0.04). Among the 28 poor responders, median levels of CD38⁺CD8⁺ T cells decreased significantly at 24 months (p < 0.0001). Levels of HLA-DR⁺CD8⁺ T cells also decreased at 24 months (p < 0.001). Levels of CD28⁺CD8⁺ T cells and levels of CD28⁺CD4⁺ T cells increased at 24 months remained unchanged. The percentage of CD38⁺CD8⁺ T cells appeared to provide a sensitive estimate of the overall immune recovery in comparison with the percentage of HLA-DR⁺CD8⁺ T cells, although this lacked specificity for the determination of early virological drug failure and did not appear to be a reliable surrogate for RNA viral load.
  
  
  CONCLUSIONS
  We show that HAART can be used successfully in Chinese populations with elevated baseline immune activation markers and that the percentage of CD38⁺CD8⁺ T cells may be an additional parameter to the current criteria for estimating the antiretroviral response with HAART.
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jiu-Cong
authors.initials: JC
authors.lastname: Zhang
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Jing
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Kang
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Sun
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D012372:ROC Curve; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D019562:Viral Load / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D018106:CD28 Antigens; D051997:ADP-ribosyl Cyclase 1