Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group

J Infect Dis. 1996 Jul;174(1):16-25. doi: 10.1093/infdis/174.1.16.


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 As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died.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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • HIV Core Protein p24 / drug effects
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • Humans
  • Infant
  • Lamivudine
  • Male
  • Pancreatitis / chemically induced
  • RNA, Viral / drug effects
  • Risk Factors
  • Treatment Outcome
  • Zalcitabine / adverse effects
  • Zalcitabine / analogs & derivatives*
  • Zalcitabine / pharmacokinetics
  • Zalcitabine / therapeutic use


  • Antiviral Agents
  • HIV Core Protein p24
  • RNA, Viral
  • Lamivudine
  • Zalcitabine