title: Fixed duration interruptions are inferior to continuous treatment in African adults starting therapy with CD4 cell counts < 200 cells/microl.
abstract: BACKGROUND
  Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation.
  
  
  METHODS
  An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count < 200 cells/microl at ART initiation, 813 with > or = 300 cells/microl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405).
  
  
  RESULTS
  Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02).
  
  
  CONCLUSIONS
  Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count >/= 300 cells/microl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
authors: MRC Clinical Trials Unit, 222 Euston Rd, London, NW12DA, UK.
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000209:etiology; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D002177:Candidiasis / Q000209:etiology; D018450:Disease Progression; D004334:Drug Administration Schedule; D004935:Esophageal Diseases / Q000209:etiology; D005260:Female; D006678:HIV; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014454:Uganda; D015215:Zidovudine; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D015215:Zidovudine