title: Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure.
  
  
  METHODS
  HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure.
  
  
  RESULTS
  A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001).
  
  
  CONCLUSIONS
  Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored.
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Bioinformatics Research Laboratory, Faculty of Science.
authors.forename: Rapeepan
authors.initials: R
authors.lastname: Suaysod
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ngo-Giang-Huong
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salvadori
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: Department of Pediatrics, Nakornping Hospital, Chiang Mai.
authors.forename: Suparat
authors.initials: S
authors.lastname: Kanjanavanit
authors.affiliation: Department of Pediatrics, Phayao Provincial Hospital.
authors.forename: Pornchai
authors.initials: P
authors.lastname: Techakunakorn
authors.affiliation: Department of Pediatrics, Samutsakhon Hospital.
authors.forename: Sawitree
authors.initials: S
authors.lastname: Krikajornkitti
authors.affiliation: Department of Pediatrics, Kalasin Hospital, Thailand.
authors.forename: Sakulrat
authors.initials: S
authors.lastname: Srirojana
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
authors.forename: Laddawan
authors.initials: L
authors.lastname: Laomanit
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
authors.forename: Suwalai
authors.initials: S
authors.lastname: Chalermpantmetagul
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Marc
authors.initials: M
authors.lastname: Lallemant
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Harvard T.H. Chan School of Public Health, Boston, Massachusetts Institut National d'Etudes Démographiques, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Cœur
authors.affiliation: Boston Children's Hospital and Harvard Medical School, Massachusetts.
authors.forename: Kenneth
authors.initials: K
authors.lastname: McIntosh
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Statistics, Faculty of Science Center of Excellence for Innovation in Analytical Science and Technology, Chiang Mai University, Thailand.
authors.forename: Patrinee
authors.initials: P
authors.lastname: Traisathit
authors.affiliation: Institut de Recherche pour le Développement, UMI 174-PHPT Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Gonzague
authors.initials: G
authors.lastname: Jourdain
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral
keywords: HIV-infected children; antiretroviral therapy failure; genotypic resistance; protease inhibitor; second-line ART