Stavudine (d4T) is a pyrimidine nucleoside analogue with potent in vitro anti-HIV activity. The drug has consistent and predictable pharmacokinetic properties. In children, total daily d4T doses of 1 and 2 mg/kg/day (in two divided doses) produce mean exposures equivalent to those achieved in adults receiving doses of 0.5 and 1 mg/kg/day,respectively. Appreciable d4T concentrations are found in cerebrospinal fluid. The drug is remarkably well-tolerated and safe. Dose-related clinical or laboratory adverse events were not observed in a recent pediatric phase I/II trial. Clinical and laboratory evidence of activity (improved growth and neurodevelopment; CD4+ lymphocyte count increases)was observed. An ongoing pilot study of combination therapy with d4T and didanosine (ddl) for children with advanced HIV disease shows absence of clinical pharmacokinetic interactions between the drugs, and excellent tolerance and safety. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. Marked increases in CD4+ lymphocyte counts have been observed in children with baseline counts greater than 50 cells/microliters. Other studies which are ongoing or in development include multicenter, randomized comparative trials of d4T and zidovudine (ZDV) for initial therapy of symptomatic HIV-infected children, and ddI alone, d4T alone, and d4T and ddI in combination for HIV-infected children who already have had long-term ZDV therapy.

Antiviral Agents/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE CD4 Lymphocyte Count Child HIV Infections/*DRUG THERAPY Human Stavudine/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE ABSTRACT

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