title: Safety of zidovudine/lamivudine scored tablets in children with HIV infection in Europe and Thailand.
abstract: BACKGROUND
  Zidovudine (ZDV) has been associated with risk of haematological toxicity. Safety data from clinical trials is generally limited to 48 weeks. We assessed the short- and mid-term toxicity of ZDV/lamivudine (3TC) fixed-dose combination scored tablets in HIV-infected children followed in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) network.
  
  
  METHODS
  Fourteen cohorts provided data on patients <18 years of age taking ZDV/3TC scored tablets between 2008 and 2012. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory adverse events (AEs) for hepatobiliary and haematological disorders were estimated by duration on drug (<12, 12-24, >24 months). Clinical adverse events and reasons for tablet discontinuation were described.
  
  
  RESULTS
  Of 541 patients on ZDV/3TC, 388 (72%) had weight and dose data available, of whom 350 (90%) weighed ≥14 kg and were eligible for tablet use; 161 (41%) were aged <10 years on an approved dose, 189 (49%) aged ≥10 years on an approved dose, and 30 (8%) were on an unapproved dose. Median age at ZDV/3TC start was 10 years, and 79% had taken ART previously (60% had prior exposure to ZDV/3TC). Overall rates of grade ≥3 AEs for absolute neutrophil counts, bilirubin, haemoglobin, platelet counts, white blood cell counts (WBC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were ≤2/100 person years (PY) for patients taking approved doses. Two hundred thirty-three (43%) patients were not on ZDV/3TC tablets at most recent follow-up; a small number (17 (7%)) discontinued due to AEs (17 (7%)), and the most common reason for discontinuation was treatment simplification (73 (31%)).
  
  
  CONCLUSIONS
  Scored ZDV/3TC tablets, both approved and taken off-label, appear to be well tolerated with few side effects. Few patients discontinued treatment due to toxicity. As ZDV/3TC tablets are taken with other antiretrovirals, it is difficult to infer association between toxicities and specific agents, highlighting the importance of widening long-term pharmacovigilance to a broader spectrum of drug combinations.
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D005060:Europe; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D013607:Tablets; D013785:Thailand; D015215:Zidovudine / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D013607:Tablets; D019259:Lamivudine; D015215:Zidovudine
keywords: Antiretroviral therapy; Children; HIV; NRTIs; Pharmacovigilance