A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection

Objectives. To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretr oviral agents, in symptomatic human immunodeficiency virus (HIV)-infected c hildren. Methods. HIV-infected children discontinued prior antiretroviral therapy an d 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 f or 12 weeks (n = 8). Children then were randomized to receive a second nucl eoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudi ne), 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 concent ration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice dail y. One case each of hypersensitivity reaction and peripheral neuropathy occ urred during abacavir monotherapy. Three children experienced neutropenia w hile receiving abacavir in combination with another antiretroviral agent. M ean 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 a ssess the antiviral activity of abacavir in children and adults.