title: Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection.
abstract: BACKGROUND
  Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood.
  
  
  METHODS
  We prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months.
  
  
  RESULTS
  Soon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies of Env-specific memory cytotoxic T lymphocytes had a median level of plasma HIV-1 RNA about one third that of the patients with lower frequencies, (median number of RNA copies per milliliter, 22,000 vs. 62,000; P=0.006). Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05).
  
  
  CONCLUSIONS
  In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
authors.affiliation: Department of Medicine, School of Medicine, University of Washington, Seattle, USA.
authors.forename: L
authors.initials: L
authors.lastname: Musey
authors.forename: J
authors.initials: J
authors.lastname: Hughes
authors.forename: T
authors.initials: T
authors.lastname: Schacker
authors.forename: T
authors.initials: T
authors.lastname: Shea
authors.forename: L
authors.initials: L
authors.lastname: Corey
authors.forename: M J
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D012367:RNA, Viral