The safety and antiviral effect of protease inhibitors in children

Study Objective. To determine the safety and antiviral effect of protease i nhibitors (PIs) over 36 months in pediatric patients infected with the huma n immunodeficiency virus (HIV). Design. Observational study. Setting. Pediatric immunodeficiency clinic. Patients. Twenty-one children. Intervention. Demographics, dosage regimens, genotype data, viral RNA and C D4(+) lymphocyte counts, adverse drug events (ADEs), laboratory tests, and compliance were evaluated over 3 years. Data were analyzed by chi (2) repea ted measures analysis of variance, and paired t tests. Measurements and Main Results. Twenty-one pediatric patients (aged 3 mo-15 yrs) received PIs over the study period. Average daily doses were ritonavir 26 mg/kg in 12 patients, nelfinavir 94 mg/kg in 16, indinavir 49 mg/kg in 5, and saquinavir 43 mg/kg in 4. Five patients developed resistance to an e xisting PI. Overall compliance was 70%. Baseline HIV-1 RNA plasma concentra tions were significantly higher than average follow-up concentrations durin g 3-36 months in patients taking ritonavir (p<0.001) and nelfinavir (p<0.00 1). Sample size was insufficient for indinavir or saquinavir. Sixty ADEs oc curred, diarrhea being most common. Of patients with ADEs, 55% required inc reased monitoring and 43% treatment. Ritonavir was associated with the most ADEs (28), followed by nelfinavir (16), indinavir (11), and saquinavir (5) . Significant increases between baseline and follow-up cholesterol levels w ere found with ritonavir (p=0.02) and nelfinavir (p=0.001), and for serum c reatinine (p=0.02) and triglycerides (p=0.02) with ritonavir. Follow-up tri glycerides were significantly higher than baseline for indinavir (p=0.003). Conclusion. Nelfinavir and ritonavir were effective in decreasing HIV-1 vir al loads and improving CD4(+) lymphocyte counts. Ritonavir was associated w ith more ADEs than other PIs. Changes in cholesterol, serum creatinine, and triglycerides were noted with some PIs.