title: Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy.
abstract: BACKGROUND
  Approximately 20% of human immunodeficiency virus type 1 (HIV-1)--infected adults do not normalize their CD4(+) T lymphocytes after long-term effective highly active antiretroviral therapy (HAART). The mechanistic basis for this failure is unclear.
  
  
  METHODS
  Seventy-four patients were followed up regularly for 3-7 years. Patients with undetectable plasma viral load (<50 copies/mL) for over 12 months were further classified into 2 groups: (1) immunological nonresponders, whose CD4(+) T-cell count was < 200/μL or <20% compared with baseline; and (2) immunological responders, whose CD4(+) T-cell count was > 300/μL or >30% compared with baseline.
  
  
  RESULTS
  Compared with 17 immunological responders, 13 immunological nonresponders had a lower magnitude of naive CD4(+) T-cell increase, a lower percentage of recent thymic immigrants (CD31(+)%), and a higher percentage of activated CD8(+) T cells. Furthermore, unlike CD4(+) T cells, which increased along with the decrease of viral load, the percentage of recent thymic immigrants (CD31(+)%) had little change in the majority of patients. These data were fit into a mathematical model, , from which we deduced that the initial rate of CD4(+) T-cell restoration is associated significantly with the percentage of recent thymic immigrants (CD31(+)%).
  
  
  CONCLUSIONS
  Our data indicate that the failure to restore CD4(+) T-cell count following HAART was associated primarily with a defect in recent thymic immigrants, which suggests the existence of thymus exhaustion.
authors.affiliation: Department of Infectious Disease, Peking Union Medical College Hospital, and Chinese Academy of Medical Sciences, Beijing, China. litsh@263.net
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Qiu
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents