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Medline ® Abstract for Reference 51

of 'ERCP for pancreatic disease in children'

Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children.
Van Dyke RB, Wang L, Williams PL, Pediatric AIDS Clinical Trials Group 219C Team
J Infect Dis. 2008;198(11):1599.
BACKGROUND: Human immunodeficiency virus (HIV) therapy includes a backbone of nucleoside reverse-transcriptase inhibitors (NRTIs). Toxicities associated with NRTIs are not fully defined in children.
METHODS: We studied 2233 children<or =13 years of age who were perinatally infected with HIV and were receiving>or =2 NRTIs, to determine the relative toxicities of the 5 most common NRTI pairs: zidovudine (ZDV)/lamivudine (3TC), ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC. Incidence rates for clinical and laboratory toxicities were estimated, and NRTI pairs were compared with regard to the time to the first toxicity.
RESULTS: The most common clinical toxicities noted were hepatitis, peripheral neuropathy, lipodystrophy/lipoatrophy, and pancreatitis, whereas the most common laboratory toxicities were an elevated anion gap, an increased total amylase level, neutropenia, and thrombocytopenia. Overall, regimens containing ZDV were associated with a significantly lower rate of clinical toxicities than were those containingd4T (adjusted hazard ratio [HR], 0.49; P = .02) ); regimens containing ddI were associated with a significantly lower rate of laboratory toxicities than were those containing 3TC (adjusted HR, 0.78; P = .04). ZDV/3TC was associated with a lower rate of clinical toxicities than were d4T/ddI and ddI/3TC and with a higher rate of laboratory toxicities than was ZDV/ddI. ZDV/ddI was associated with a lower rate of clinical toxicities than was d4T/3TC.
CONCLUSIONS: In children, regimens containing ZDV have less toxicity than do those containing d4T, thereby supporting their use in first-line regimens. D4T/3TC, d4T/ddI, and ddI/3TC have similar toxicity rates and are appropriate for second-line therapy.
Department of Pediatrics, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. vandyke@tulane.edu