title: Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis.
abstract: BACKGROUND
  Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug.
  
  
  METHODS
  We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0-18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models.
  
  
  RESULTS
  Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2·2% (95% CI 0·4-5·2); treatment switching or discontinuation (seven studies) pooled incidence was 10·9% (2·1-24·3); of grade 3-4 adverse events (six studies) pooled incidence was 9·9% (2·4-20·9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21·5% (2·8-48·4). Between-study inconsistency was significant for all outcomes (p<0·0001 for all inconsistencies). Incidence of death (four studies) was 3·3% (95% CI 1·5-5·6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1·08; 95% CI 0·19-6·15), grade 3 or 4 events (0·79 [0·44-1·42]), or death (1·72 [0·77-3·82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir.
  
  
  CONCLUSIONS
  Abacavir-related toxicity occurs early after ART initiation and is manageable. Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents, especially in sub-Saharan Africa were HLA B5701 genotype is rare.
  
  
  BACKGROUND
  WHO.
authors: Inserm, U897, University of Bordeaux, ISPED, Bordeaux, France.
authors: Julie
authors: J
authors: Jesson
authors: Centre de Recherche Internationale pour la Santé, Projet MONOD ANRS 12206, Ouagadougou, Burkina Faso.
authors: Désiré L
authors: DL
authors: Dahourou
authors: Department of HIV/AIDS, WHO, Geneva, Switzerland.
authors: Françoise
authors: F
authors: Renaud
authors: Department of HIV/AIDS, WHO, Geneva, Switzerland.
authors: Martina
authors: M
authors: Penazzato
authors: Inserm, U897, University of Bordeaux, ISPED, Bordeaux, France. Electronic address: valeriane.leroy@inserm.fr.
authors: Valériane
authors: V
authors: Leroy
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002662:Child Health Services; D002675:Child, Preschool; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D064887:Observational Studies as Topic; D017410:Practice Guidelines as Topic; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir