title: CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy.
abstract: BACKGROUND
  CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course.
  
  
  METHODS
  In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment.
  
  
  CONCLUSIONS
  CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up.
  
  
  CONCLUSIONS
  These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Killian
authors.forename: Jeremy
authors.initials: J
authors.lastname: Roop
authors.forename: Sharon
authors.initials: S
authors.lastname: Ng
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Jay A
authors.initials: JA
authors.lastname: Levy
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002452:Cell Count; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015415:Biomarkers; D004279:DNA, Viral