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Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine
K M Butler1, D Venzon, N Henry
1Pediatric Branch, National Cancer Institute, Bethesda, MD 20892.
Insights
High-dose dideoxyinosine (ddI) increases pancreatitis risk in children with HIV. Pancreatitis developed in 7% of patients, resolving upon ddI withdrawal, with higher doses linked to increased risk.
Area of Science:
- Pediatric Infectious Diseases
- Clinical Pharmacology
- Gastroenterology
Background:
- Human immunodeficiency virus (HIV)-infected children often receive nucleoside reverse transcriptase inhibitors.
- Dideoxyinosine (ddI) is one such antiretroviral medication with known toxicities.
- Pancreatitis is a serious potential adverse event associated with ddI therapy.
Purpose of the Study:
- To identify predictive or contributory risk factors for pancreatitis in pediatric HIV patients receiving ddI.
- To evaluate the relationship between ddI dosage and pancreatitis incidence.
Main Methods:
- Prospective evaluation of 95 HIV-infected children (3 months to 18 years) receiving ddI.
- Dose levels ranged from 60 to 540 mg/m2 per day for a mean of 56 weeks.
- Monitoring for pancreatitis and assessment of potential risk factors including age, sex, CD4 count, disease type, and ddI dose.
Main Results:
- Pancreatitis occurred in 7% of patients (7 of 95), resolving upon ddI discontinuation.
- Pancreatitis was associated with higher ddI doses (≥360 mg/m2/day) compared to lower doses (< or =270 mg/m2/day).
- Patients who developed pancreatitis received a higher mean daily ddI dose (348 mg/m2) than those without pancreatitis (282 mg/m2).
Conclusions:
- Higher doses of dideoxyinosine (ddI) are a significant risk factor for pancreatitis in HIV-infected children.
- Dose reduction or cessation of ddI is crucial for managing and preventing pancreatitis.
- Further research may be needed to confirm the relationship between ddI plasma concentration and pancreatitis risk.
Abstract:
To define predictive or contributory risk factors for pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine (ddI), the authors evaluated 95 children, 3 months to 18 years of age, who had received ddI at 60 to 540 mg/m2 per day for a mean of 56 weeks. Pancreatitis developed in 7 patients (7%) but resolved in all upon withdrawal of ddI. Neither age, sex, nor CD4 count at study entry was predictive of pancreatitis, but pancreatitis appeared more likely to develop in hemophiliacs than in other patients (4 of 23 vs 3 of 72). Pancreatitis developed only in patients who received ddI at the highest dose levels (7 of 60 patients who received ddI at a dose > or = 360 mg/m2 per day vs 0 of 35 patients who received < or = 270 mg/m2 per day). Patients in whom pancreatitis developed had received a higher mean daily dose of ddI than patients with normal amylase and lipase levels throughout the study (348 mg/m2 vs 282 mg/m2), but no relationship with the cumulative dose or the duration of ddI therapy was observed. Although a statistically significant relationship between ddI plasma concentration (area under the curve) and pancreatitis was not conclusively demonstrated, as the number of patients in whom pancreatitis actually developed was small, such a relationship may have been obscured.(ABSTRACT TRUNCATED AT 250 WORDS)