Toxicities Associated with Dual Nucleoside Reverse‐Transcriptase Inhibitor Regimens in HIV‐Infected Children
Year: 2008
Type: article
Study design: Observational Study
Abstract: 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 containing d4T (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.
DOI: 10.1086/593022
Institutions: Tulane University, Harvard University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1306602114, NICHD INTERNATIONAL PEDIATRIC AND PERINATAL HIV STUDIES NETWORK COORDINATING CEN, G2063336705, Statistical and Data Management Center-Pediatric,Adolescent, and Maternal CTG, General Clinical Research Center, Integrated University of Puerto Rico Clinical Trials Unit, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, GENERAL CLINICAL RESEARCH CENTER, Statistical/Data Management Center-Pediatric AIDS CTG, G767300504, G9000141709
OpenAlex ID: W2107574856