title: Outcomes after viral load rebound on first-line antiretroviraltreatment in children with HIV in the UK and Ireland: an observational cohort study.
abstract: BACKGROUND
  About a third of children with HIV have virological failure within 2 years of beginning antiretroviral treatment (ART). We assessed the probability of switch to second-line ART or virological re-suppression without switch in children who had virological rebound on first-line ART in the UK and Ireland.
  
  
  METHODS
  In this study, we used data reported to the Collaborative HIV Paediatric Study (CHIPS), a national multicentre observational cohort. We included children with virological rebound (confirmed viral load>400 copies per mL after suppression<400 copies per mL) on first-line ART. We did a competing-risk analysis to estimate the probability of switch to second-line treatment, confirmed resuppression (two consecutive viral load measurments<400 copies per mL) without switch, and continued viral load above 400 copies per mL without switch. We also assessed factors that predicted a faster time to switch.
  
  
  RESULTS
  Of the 900 children starting first-line ART who had a viral load below 400 copies per mL within a year of starting treatment, 170 (19%) had virological rebound by a median of 20·6 months (IQR 9·7–40·5). At rebound, median age was 10·6 years (5·6–13·4), median viral load was 3·6 log10 copies per mL (3·1–4·2), and median CD4% was 24% (17–32). 89 patients (52%) switched to second-line ART at a median of 4·9 months (1·7–13·4) after virological rebound, 53 (31%) resuppressed without switch (19 [61%] of 31 patients on a first-line regimen that included a protease inhibitor and 31 [24%] of 127 patients on a first-line regimen that included a non-nucleoside reverse transcriptase inhibitor; NNRTI), and 28 (16%) neither resuppressed nor switched. At 12 months after rebound, the estimated probability of switch was 38% (95% CI 30–45) and of resuppression was 27% (21–34). Faster time to switch was associated with a higher viral load (p<0·0001), later calendar year at virological rebound (p=0·02), and being on an NNRTI-based or triple nucleoside reverse transcriptase inhibitor-based versus protease-inhibitor-based first-line regimen (p=0·001).
  
  
  CONCLUSIONS
  A third of children with virological rebound resuppressed without switch. Clinicians should consider the possibility of resuppression with adherence support before switching treatment in children with HIV.
  
  
  BACKGROUND
  NHS England (London Specialised Commissioning Group).
authors.forename: Tristan
authors.initials: T
authors.lastname: Childs
authors.forename: Delane
authors.initials: D
authors.lastname: Shingadia
authors.forename: Ruth
authors.initials: R
authors.lastname: Goodall
authors.affiliation: Lyall
authors.forename: Katja
authors.initials: K
authors.lastname: Doerholt
authors.forename: Hermione
authors.initials: H
authors.lastname: Lyall
authors.forename: Trinh
authors.initials: T
authors.lastname: Duong
authors.forename: Ali
authors.initials: A
authors.lastname: Judd
authors.forename: Di M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Intira Jeannie
authors.initials: IJ
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004334:Drug Administration Schedule; D004739:England / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D017410:Practice Guidelines as Topic; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors