title: Clinical significance of transient HIV type-1 viraemia and treatment interruptions during suppressive antiretroviral treatment.
abstract: BACKGROUND
  Transient episodes of HIV type-1 viraemia are frequently observed in patients on suppressive combination antiretroviral therapy (cART). We studied the effect of such episodes and of treatment interruptions on clinical outcome and immunological response.
  
  
  METHODS
  A total of 3,321 patients from the ATHENA cohort had virological suppression (HIV type-1 RNA<50 copies/ml) after 24 weeks of cART. The association between subsequent episodes of treatment interruptions, viral suppression, low-level (50-400 copies/ml) and high-level (>400 copies/ml) viraemia and the outcomes death, AIDS or immunological response (CD4(+) T-cell count increase > or =50% from 24 weeks) was studied with Poisson regression models, including either time-updated cumulative follow-up, time spent per type of episode or modelling episodes as binary status indicators.
  
  
  RESULTS
  During 11,165 person-years of follow-up, 88 patients died, 111 developed AIDS and 2,019 had an immunological response. Longer follow-up time in treatment interruptions increased the risk of AIDS (relative risk [RR] 8.07, 95% confidence interval [CI] 3.98-16.4 per year longer) and impaired immunological response (RR 0.22, 95% CI 0.12-0.41). High-level viraemia was only associated with immunological response (RR 0.55, 95% CI 0.40-0.74), whereas low-level viraemia was not associated with any of the three outcomes. Status indicator models gave similar results. When also including time-updated CD4(+) T-cell counts, the observed associations diminished.
  
  
  CONCLUSIONS
  Treatment interruptions and high-level, but not low-level, viraemia are strongly associated with clinical outcome, mainly via their effect on CD4(+) T-cell counts.
authors.affiliation: Stichting HIV Monitoring, Amsterdam, the Netherlands.
authors.forename: Shuangjie
authors.initials: S
authors.lastname: Zhang
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Colette
authors.initials: C
authors.lastname: Smit
authors.forename: Frank
authors.initials: F
authors.lastname: Kroon
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: Jan
authors.initials: J
authors.lastname: Prins
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors