Development and significance of zidovudine resistance in children infected with human immunodeficiency virus.

Decreasing susceptibility to zidovudine (ZDV) has been described in persons infected with human immunodeficiency virus (HIV) type 1 who are receiving ZDV therapy. However, the clinical significance of decreased ZDV susceptibility remains unclear. In this study, HIV isolates obtained from children with symptomatic HIV infection treated with ZDV were monitored for their susceptibility to the antiretroviral agent and correlated with disease progression. Using a peripheral blood mononuclear cell-based assay to measure ZDV susceptibility, we evaluated HIV isolates from 19 children (mean age, 6.8 years; range, 5 months to 12 years) during ZDV therapy for susceptibility to ZDV. Of the 19 children studied, 10 continued to have susceptible HIV strains during ZDV treatment, and 9 acquired resistant viruses. All eight isolates from children without previous exposure to ZDV were initially susceptible. After a median of 11 months of ZDV therapy, three (38%) of these eight children had acquired resistant HIV strains (defined as ZDV susceptibility > or = 10 mumol/L). Children with resistant strains had worse clinical outcomes than children whose viruses remained susceptible, as determined by a 50% decline in absolute CD4+ cell counts after 1 year of treatment, failure to thrive, or death. Children with resistant viruses who were given alternative antiretroviral therapy frequently responded to the new treatment with improved growth and stabilization of their HIV-related disease. These data suggest that, in HIV-infected children, ZDV-resistant HIV strains are associated with diminished drug efficacy and more rapid disease progression.