title: Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy.
abstract: BACKGROUND
  HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.
  
  
  METHODS
  Children aged 18 months to 12 years initiated first-line cART and were followed every 1-3 months, for up to 5.5 years. Treatment was switched to second-line cART based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies per milliliter. Drug resistance was assessed during viral failure by population-based sequencing.
  
  
  RESULTS
  Among 100 children on first-line cART followed for a median of 49 months, 34% children experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multiclass resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred at a median of 12 months before switching to second line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated; however, only 1 (7%) of 14 children had persistent viremia during second-line treatment.
  
  
  CONCLUSIONS
  Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second line based on clinical/immunologic criteria occurred ∼1 year after viral failure, but the delay did not consistently compromise second-line treatment.
authors.affiliation: Department of Pediatrics, University of Nairobi, Nairobi, Kenya. dalton@africaonline.co.ke
authors.forename: Dalton C
authors.initials: DC
authors.lastname: Wamalwa
authors.forename: Dara A
authors.initials: DA
authors.lastname: Lehman
authors.forename: Sarah
authors.initials: S
authors.lastname: Benki-Nugent
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Gasper
authors.forename: Richard
authors.initials: R
authors.lastname: Gichohi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007223:Infant; D007630:Kenya; D008297:Male; D016016:Proportional Hazards Models; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents