title: Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death.
abstract: BACKGROUND
  A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.
  
  
  METHODS
  Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models.
  
  
  RESULTS
  In groups A-C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection.
  
  
  CONCLUSIONS
  In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Switzerland.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Kaufmann
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Stefano
authors.initials: S
authors.lastname: Giulieri
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000517:prevention & control*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D012307:Risk Factors; D013995:Time; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents