Clinical and virologic response to combination treatment with indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 infection:A multicenter study in The Netherlands

Objective: To evaluate the clinical, immunologic, and virologic response to indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 (HIV-1) infection. Study design: Twenty-eight HIV-1 infected children (3 months to 16 years of age) with or without prior treatment with reverse-transcriptase inhibitors and a HIV-1 RNA >5000 copies/mL and/or a CD4 cell count less than the lower limit of the age- specific reference value were treated with indinavir, zidovudine, and lamivudine. Pharmacokinetics of indinavir were determined in each child. Results: The combination treatment was well tolerated in the majority of patients. Clinical improvement was seen in all patients. After 6 months of therapy, 70% of the patients had an HIV-1 RNA load below 500 copies/mL, whereas 48% of the children had a vital load below 40 copies/mL. Relative CD4 cell counts in relation to the lower limit of the age-specific reference value increased significantly from a median value of 79% at baseline to 106% after 6 months of therapy. The doses of indinavir necessary to achieve area under the curve values comparable to adult values varied from 1250 mg/m2/d to 2450 mg/m2/d. Conclusions: Highly active antiretroviral therapy consisting of indinavir, zidovudine, and lamivudine in children reduced HIV-1 RNA to less than 500 copies/mL in 70% of the children within 6 months. Improved CD4 cell counts were observed in most patients, as was a better clinical condition (no invasive or opportunistic infections, increased weight gain). Side effects of the triple therapy were mild. Highly active antiretroviral therapy can be used as successfully in children as in adults.