title: Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions.
abstract: BACKGROUND
  Excess risks for death/opportunistic disease in adults randomized to CD4-driven planned treatment interruption (PTI) in the Strategies for Management of Antiretroviral Therapy (SMART) trial remained after antiretroviral therapy (ART) re-initiation. Risks for children following PTI were evaluated in long-term follow-up of children in the PENTA 11 trial.
  
  
  METHODS
  Children with HIV RNA below 50 copies/ml and CD4 at least 30% (2-6 years) or at least 500 cells/μl (7-15 years) were randomized to continuous ART (cART) or PTI in PENTA 11 (ISRCTN 36694210). After the end of the trial, all were recommended to resume ART. Data were collected annually and analysed up to the second year of visit.
  
  
  RESULTS
  One hundred and one (51 cART, 50 PTI; median baseline age 9.2 years) children had median overall follow-up 4.6 (range 3.7-5.0) years. During 2-year post-trial period, there were no deaths or new Centers for Disease Control and Prevention (CDC) stage B/C events. Rate of clinical grade of at least two events was similar between PTI and cART [relative risk (RR) 1.03; 95% confidence interval (CI) 0.43, 2.50; P = 0.94]. At 2 years, difference in absolute CD4% between PTI and cART was -1.6% (-4.5%; 1.3%; P = 0.27), and proportions with HIV RNA below 50 copies/ml were 82 versus 86% (P = 0.57), respectively; no differences in growth or fasting lipids were observed. Key predictors of greater CD4% recovery after re-initiating ART were higher CD4% at baseline (P < 0.001) and longer time since ART re-initiation (P < 0.001). During overall follow-up, 4 (8%) PTI versus 5 (10%) CT children switched ART for failure (P = 0.75) and 9 (18%) versus 1 (2%) (P = 0.008) substituted ART for simplification.
  
  
  CONCLUSIONS
  No adverse clinical, immunological or virological consequences of PTI were observed 2 years after the end of PENTA 11 trial. Although ART interruption is not generally recommended, it may be an acceptable option for children, particularly when there is high risk of unplanned treatment interruptions.
authors.affiliation: The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. torsak.b@hivnat.org
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.forename: Trinh
authors.initials: T
authors.lastname: Duong
authors.forename: Alexandra
authors.initials: A
authors.lastname: Compagnucci
authors.forename: Paddy
authors.initials: P
authors.lastname: McMaster
authors.forename: Stefania
authors.initials: S
authors.lastname: Bernardi
authors.forename: Suparat
authors.initials: S
authors.lastname: Kanjanavanit
authors.forename: Osvalda
authors.initials: O
authors.lastname: Rampon
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.forename: Yacine
authors.initials: Y
authors.lastname: Saïdi
authors.forename: Yoann
authors.initials: Y
authors.lastname: Riault
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Diana
authors.initials: D
authors.lastname: Gibb
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002648:Child; D004279:DNA, Viral; D018450:Disease Progression; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D008297:Male; D012367:RNA, Viral; D018570:Risk Assessment; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral