| Title | CYP2C19 Genetic Variants Affect Nelfinavir Pharmacokinetics and Virologic Response in HIV-1-Infected Children Receiving Highly Active Antiretroviral Therapy. | | Author(s) | Saitoh A, Capparelli E, Aweeka F, Sarles E, Singh KK, Kovacs A, Burchett SK, Wiznia A, Nachman S, Fenton T, Spector SA | | Institution | From the *Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, CA; daggerDepartment of Clinical Pharmacology, University of California, San Francisco, CA; double daggerMaternal, Child, and Adolescent Center for Infectious Diseases and Virology, University of Southern California Keck School of Medicine, Los Angeles, CA; section signDivision of Infectious Diseases, Harvard Medical School, Boston, MA, ||Department of Pediatrics, Jacobi Medical Center, Bronx, NY; paragraph signDepartment of Pediatrics, State University of New York at Stony Brook Health Science Center, NY; and #Harvard School of Public Health, Boston, MA. | | Source | J Acquir Immune Defic Syndr 2009 Nov 3. | | Abstract | BACKGROUND:: The objective of this research was to identify the impact of genetic variants of P-glycoprotein (ABCB1) and cytochrome P450 (CYP) on nelfinavir pharmacokinetics and response to highly active antiretroviral therapy (HAART) in HIV-1-infected children.
METHODS:: HIV-1-infected children (n = 152) from Pediatric AIDS Clinical Trial Group 366 or 377 receiving nelfinavir as a component of HAART were evaluated. Genomic DNA was assayed for ABCB1 and CYP genetic variants using real-time polymerase chain reaction Nelfinavir oral clearance (CL/F), M8 to nelfinavir ratios, CD4 T cells, and HIV-1-RNA were measured during HAART.
RESULTS:: Nelfinavir CL/F and M8 to nelfinavir ratios were significantly associated with the CYP2C19-G681A genotypes (P < 0.001). Furthermore, the CYP2C19-G681A genotype was related to virologic responses at week 24 (P = 0.01). A multivariate analysis demonstrated that age (P = 0.03), concomitant protease inhibitor use (P < 0.001), and the CYP2C19-G681A genotype (P < 0.001) remained significant covariates associated with nelfinavir CL/F.
CONCLUSIONS:: CYP2C19 genotypes altered nelfinavir pharmacokinetics and the virologic response to HAART in HIV-1-infected children. These findings suggest that CYP2C19 genotypes are important determinants of nelfinavir pharmacokinetics and virologic response in HIV-1-infected children. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19890215 |
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