title: A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children.
  
  
  METHODS
  HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated.
  
  
  RESULTS
  At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy.
  
  
  CONCLUSIONS
  Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.
authors: Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
authors: M W
authors: MW
authors: Kline
authors: S
authors: S
authors: Blanchard
authors: C V
authors: CV
authors: Fletcher
authors: J L
authors: JL
authors: Shenep
authors: R E
authors: RE
authors: McKinney
authors: R C
authors: RC
authors: Brundage
authors: M
authors: M
authors: Culnane
authors: R B
authors: RB
authors: Van Dyke
authors: W M
authors: WM
authors: Dankner
authors: A
authors: A
authors: Kovacs
authors: J A
authors: JA
authors: McDowell
authors: S
authors: S
authors: Hetherington
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D012367:RNA, Viral / Q000097:blood; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D000099227:Abacavir