Display options
Cite
Kitchen CM, Kroll J, Kuritzkes DR, et al. Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment. Comput Stat Data Anal. 2009;53(3):766-775doi: 10.1016/j.csda.2008.06.007.
Kitchen, C. M., Kroll, J., Kuritzkes, D. R., Bloomquist, E., Deeks, S. G., & Suchard, M. A. (2009). Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment. Computational statistics & data analysis, 53(3), 766-775. https://doi.org/10.1016/j.csda.2008.06.007
Kitchen, Christina M R, et al. "Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment." Computational statistics & data analysis vol. 53,3 (2009): 766-775. doi: https://doi.org/10.1016/j.csda.2008.06.007
Kitchen CM, Kroll J, Kuritzkes DR, Bloomquist E, Deeks SG, Suchard MA. Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment. Comput Stat Data Anal. 2009 Jan 15;53(3):766-775. doi: 10.1016/j.csda.2008.06.007. PMID: 20442796; PMCID: PMC2862497.
Copy Download .nbib Format: NLM
Share it on

Comput Stat Data Anal. 2009 Jan 15;53(3):766-775. doi: 10.1016/j.csda.2008.06.007.

Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment.

Computational statistics & data analysis

Christina M R Kitchen, Jing Kroll, Daniel R Kuritzkes, Erik Bloomquist, Steven G Deeks, Marc A Suchard

Affiliations

  1. Department of Biostatistics, University of California, Los Angeles, CA, United States.

PMID: 20442796 PMCID: PMC2862497 DOI: 10.1016/j.csda.2008.06.007

Abstract

Enfuvirtide (ENF) is a fusion inhibitor that prevents the entry of HIV virions into target cells. Studying the characteristics of viral evolution during treatment and after a treatment interruption can lend insight into the mechanisms of viral evolution and fitness. Although interruption of anti-HIV therapy often results in rapid emergence of an archived "wild-type" virus population, previous work from our group indicates that when only ENF is interrupted, viral gp41 continues to evolve forward and resistance mutations are lost due to back-mutation and remodeling of the envelope protein. To examine the co-evolution of gp120 and gp41 during ENF interruption we extend the Bayesian Hierarchical Phylogenetic model (HPM). Current HPMs enforce conditional independence across all outcomes while biologically all gene regions within a patient should return the same tree unless recombination confers an evolutionary selective advantage. A two-way-interaction HPM is proposed that provides middle ground between these two extremes and allows us to test for differences in evolutionary pressures across gene regions in multiple patients simultaneously. When the model is applied to a well-characterized cohort of HIV-infected patients interrupting ENF we find that across patients, the virus continued to evolve forward in both gene regions. Overall, the hypothesis of independence over dependence between the gene regions is supported. Models that allow for the examination of co-evolution over time will be increasingly important as more therapeutic classes are developed, each of which may impact other through novel and complex mechanisms.

References

  1. AIDS. 2000 Dec 22;14(18):2857-67 - PubMed
  2. J Clin Virol. 2005 Dec;34(4):288-94 - PubMed
  3. Ann Intern Med. 1999 Jun 15;130(12):1005-13 - PubMed
  4. Syst Biol. 2003 Oct;52(5):649-64 - PubMed
  5. Science. 1998 Jun 19;280(5371):1884-8 - PubMed
  6. Bioinformatics. 2005 Jul 1;21(13):3034-42 - PubMed
  7. J Virol. 2002 Jul;76(14):7000-9 - PubMed
  8. J Virol. 2004 Oct;78(20):11296-302 - PubMed
  9. J Infect Dis. 2007 Feb 1;195(3):387-91 - PubMed
  10. J Clin Microbiol. 1995 Apr;33(4):906-11 - PubMed
  11. J Virol. 2007 Apr;81(7):3240-50 - PubMed
  12. AIDS. 2000 Dec 22;14(18):2937-9 - PubMed
  13. J Acquir Immune Defic Syndr. 2006 Sep;43(1):60-4 - PubMed
  14. J Virol. 2006 Sep;80(17):8807-19 - PubMed
  15. J Infect Dis. 2007 Feb 1;195(3):318-21 - PubMed
  16. AIDS Res Hum Retroviruses. 2006 Dec;22(12):1260-6 - PubMed
  17. J Virol. 2003 Dec;77(24):13376-88 - PubMed
  18. J Virol. 1992 Nov;66(11):6777-80 - PubMed
  19. Mol Biol Evol. 1993 May;10(3):512-26 - PubMed
  20. AIDS. 2003 Feb 14;17(3):361-70 - PubMed
  21. Comput Appl Biosci. 1997 Jun;13(3):235-8 - PubMed
  22. J Infect Dis. 2003 Oct 1;188(7):977-85 - PubMed
  23. J Infect Dis. 2006 Jul 15;194(2):238-46 - PubMed

Publication Types

Grant support