title: Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.
abstract: The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.
authors.affiliation: Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Lewis
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: J
authors.initials: J
authors.lastname: Church
authors.forename: M
authors.initials: M
authors.lastname: Farley
authors.forename: S
authors.initials: S
authors.lastname: Wheeler
authors.forename: A
authors.initials: A
authors.lastname: Keller
authors.forename: M
authors.initials: M
authors.lastname: Rubin
authors.forename: G
authors.initials: G
authors.lastname: Yuen
authors.forename: B
authors.initials: B
authors.lastname: Mueller
authors.forename: M
authors.initials: M
authors.lastname: Sloas
authors.forename: L
authors.initials: L
authors.lastname: Wood
authors.forename: F
authors.initials: F
authors.lastname: Balis
authors.forename: G M
authors.initials: GM
authors.lastname: Shearer
authors.forename: P
authors.initials: P
authors.lastname: Brouwers
authors.forename: J
authors.initials: J
authors.lastname: Goldsmith
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D016655:HIV Core Protein p24 / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D019259:Lamivudine; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced; D012367:RNA, Viral / Q000187:drug effects; D012307:Risk Factors; D016896:Treatment Outcome; D016047:Zalcitabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D016655:HIV Core Protein p24; D012367:RNA, Viral; D019259:Lamivudine; D016047:Zalcitabine