title: Antiretroviral treatment failure, drug resistance, and subtype diversity in the only pediatric HIV clinic in Rhode Island.
abstract: BACKGROUND
  Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART.
  
  
  METHODS
  We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests.
  
  
  RESULTS
  Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated.
  
  
  CONCLUSIONS
  We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.
authors: Department of Pediatrics.
authors: Tanya
authors: T
authors: Rogo
authors: Center for Statistical Sciences.
authors: Allison K
authors: AK
authors: DeLong
authors: Division of Infectious Diseases, Brown University, Providence, Rhode Island.
authors: Philip
authors: P
authors: Chan
authors: Division of Infectious Diseases, Brown University, Providence, Rhode Island.
authors: Rami
authors: R
authors: Kantor
mesh_terms: D000293:Adolescent; D000553:Ambulatory Care; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010372:Pediatrics; D010802:Phylogeny; D012237:Rhode Island / Q000453:epidemiology; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
keywords: HIV; antiretroviral resistance; pediatrics; subtype
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