title: Frequency of stavudine substitution due to toxicity in children receiving antiretroviral treatment in sub-Saharan Africa.
abstract: BACKGROUND
  Stavudine is a commonly used drug in paediatric antiretroviral treatment (ART) regimens. Due to toxicity concerns, however, the drug abacavir has replaced stavudine in first-line paediatric regimens in many countries. We describe the frequency of stavudine toxicity in children receiving ART at a treatment clinic in Soweto, South Africa.
  
  
  METHODS
  Data on patient characteristics and outcomes of ART were collected from a cohort of 2222 HIV-infected children initiating ART between 2004 and 2008 when stavudine-containing regimens were routinely recommended. At several time-points after treatment initiation, we estimate the proportion of children where an attending clinician discontinued stavudine due to lipodystrophy, pancreatitis, lactic acidosis or peripheral neuropathy. Factors associated with stavudine-related toxicities were identified.
  
  
  RESULTS
  At ART initiation, most children had advanced disease. The majority initiated an efavirenz/lamivudine/stavudine regimen (n = 1422), and 76% of children remained on their initial ART regimen after a median 19.9 months of ART. Replacement of stavudine due to drug toxicity occurred at a rate of 28.8 per 1000 child years on treatment (95% confidence interval = 23.6-35.2). Rates of toxicity increased with treatment duration (in their first year of ART stavudine was replaced in 0.5% of children, but after 3 years stavudine had been changed to abacavir in 12.6% of children). Toxicity was more common in older children and in girls. Lipodystrophy accounted for 87 of 96 toxic events.
  
  
  CONCLUSIONS
  Stavudine-associated toxicity resulting in single-drug substitution was uncommon in this cohort, though its frequency increased steadily with ART duration, especially with lipodystrophy. Where drug options are limited, stavudine remains a relatively well tolerated and effective option for children.
authors.affiliation: Department of Paediatrics, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
authors.forename: Megan
authors.initials: M
authors.lastname: Palmer
authors.forename: Matthew
authors.initials: M
authors.lastname: Chersich
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.forename: Lee
authors.initials: L
authors.lastname: Fairlie
authors.forename: Tammy
authors.initials: T
authors.lastname: Meyers
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D013019:South Africa; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019259:Lamivudine; D018119:Stavudine; D000099227:Abacavir; C098320:efavirenz