Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338) Public Deposited

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Creator
  • Petch, Leslie A
    • Affiliation: School of Medicine, UNC Center for AIDS Research
  • Mofenson, Lynne M
    • Other Affiliation: Pediatric, Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA
  • Fiscus, Susan
    • Affiliation: School of Medicine, Department of Microbiology and Immunology, UNC Center for AIDS Research
  • Nachman, Sharon A
    • Other Affiliation: Department of Pediatrics, SUNY Health Science Center at Stony Brook, Stony Brook, NY, USA
  • McIntosh, Kenneth
    • Other Affiliation: Division of Infectious Diseases, Children's Hospital and Harvard Medical School, Boston, MA, USA
  • Napravnik, Sonia
    • Affiliation: School of Medicine, UNC Center for AIDS Research
  • Pelton, Stephen I
    • Other Affiliation: Department of Pediatrics, Boston Medical Center, Boston, MA, USA
  • Wiznia, Andrew A
    • Other Affiliation: Department of Pediatrics, Jacobi Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA
  • Yogev, Ram
    • Other Affiliation: Division of Infectious Diseases, Children's Memorial Hospital and Northwestern University School of Medicine, Chicago, IL, USA
  • Stanley, Kenneth
    • Other Affiliation: Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
  • Kovacs, Andrea
    • Other Affiliation: Maternal, Child and Adolescent Program, University of Southern California Medical Center, Los Angeles, CA, USA
  • Hu, Chengcheng
    • Other Affiliation: Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
Abstract
  • Abstract Background The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. Results There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.
Date of publication
Identifier
  • doi:10.1186/1742-6405-4-2
  • 17280617
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Susan A Fiscus et al.; licensee BioMed Central Ltd.
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Journal title
  • AIDS Research and Therapy
Journal volume
  • 4
Journal issue
  • 1
Page start
  • 2
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1742-6405
Bibliographic citation
  • AIDS Research and Therapy. 2007 Feb 06;4(1):2
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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