title: Association between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.
abstract: OBJECTIVE
  Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited.
  
  
  OBJECTIVE
  To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment.
  
  
  METHODS
  Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana.
  
  
  METHODS
  The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis.
  
  
  RESULTS
  With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses.
  
  
  CONCLUSIONS
  Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.
authors: Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. lowenthale@email.chop.edu
authors: Elizabeth D
authors: ED
authors: Lowenthal
authors: Jonas H
authors: JH
authors: Ellenberg
authors: Edwin
authors: E
authors: Machine
authors: Aditi
authors: A
authors: Sagdeo
authors: Sefelani
authors: S
authors: Boiditswe
authors: Andrew P
authors: AP
authors: Steenhoff
authors: Richard
authors: R
authors: Rutstein
authors: Gabriel
authors: G
authors: Anabwani
authors: Robert
authors: R
authors: Gross
mesh_terms: D000293:Adolescent; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D001902:Botswana; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D012044:Regression Analysis; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D019829:Nevirapine; C098320:efavirenz
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