Table of Contents
International Journal of Computational Mathematics
Volume 2014, Article ID 659675, 17 pages
http://dx.doi.org/10.1155/2014/659675
Research Article

Modelling Hepatotoxicity of Antiretroviral Therapy in the Liver during HIV Monoinfection

1Department of Mathematics, Faculty of Science Education, Busitema University, P.O. Box 236, Tororo, Uganda
2Department of Mathematics, School of Physical Sciences, College of Natural Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda
3Department of Pharmacology and Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda

Received 13 May 2014; Revised 10 September 2014; Accepted 17 September 2014; Published 19 October 2014

Academic Editor: Baojun Song

Copyright © 2014 Hasifa Nampala et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Babu, K. Suwansrinon, G. Bren, A. Badley, and S. Rizza, “HIV induces TRAIL sensitivity in hepatocytes,” PLoS ONE, vol. 4, no. 2, Article ID e4623, 2009. View at Publisher · View at Google Scholar
  2. J. McKoy, C. Bennett, M. Scheetz et al., “Hepatotoxicity associated with long-versus short-course HIV prophylactic nevirapine use: a systematic review and meta-analysis from the research on adverse drug events and reports (RADAR) project,” Journal of Viral Hepatitis, vol. 32, no. 2, pp. 147–158, 2009. View at Google Scholar
  3. E. H. Gisolf, C. Dreezen, S. A. Danner, J. L. F. Weel, and G. J. Weverling, “Risk factors for hepatotoxicity in HIV-1-infected patients receiving ritonavir and saquinavir with or without stavudine,” Clinical Infectious Diseases, vol. 31, no. 5, pp. 1234–1239, 2000. View at Publisher · View at Google Scholar · View at Scopus
  4. D. Iser and S. Lewin, “The pathogenesis of liver disease in the setting of HIV-hepatitis B virus coinfection,” Antiviral Therapy, vol. 14, no. 2, pp. 155–164, 2009. View at Google Scholar · View at Scopus
  5. M. K. Jain, C. K. Opio, C. C. Osuagwu, R. Pillai, P. Keiser, and W. M. Lee, “Do HIV care providers appropriately manage hepatitis B in coinfected patients treated with antiretroviral therapy?” Clinical Infectious Diseases, vol. 44, no. 7, pp. 996–1000, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. M. L. Landrum, A. M. Fieberg, H. M. Chun et al., “The effect of human immunodeficiency virus on hepatitis B virus serologic status in co-infected adults,” PLoS ONE, vol. 5, no. 1, Article ID e8687, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Nampala, L. S. Luboobi, J. Y. Mugisha, and C. Obua, “Mathematical modeling of liver enzyme elevation in HIV mono-infection,” Mathematical Biosciences, vol. 242, no. 1, pp. 77–85, 2013. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  8. P. Xiao, O. Usami, Y. Suzuki et al., “Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4,” AIDS, vol. 22, no. 14, pp. 1749–1757, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. J. T. Blackard and K. E. Sherman, “HCV/HIV co-infection: time to re-evaluate the role of HIV in the liver?” Journal of Viral Hepatitis, vol. 15, no. 5, pp. 323–330, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Crane, K. Visvanathan, and S. R. Lewin, “HIV infection and TLR signalling in the liver,” Gastroenterology Research and Practice, vol. 2012, Article ID 473925, 8 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Balagopal, S. C. Ray, R. M. de Oca et al., “Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution,” AIDS, vol. 23, no. 18, pp. 2397–2404, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. C. Liddle and C. Stedman, Hepatic Metabolism of Drugs, Wiley-Blackwell, 2007.
  13. N. J. Hewitt, M. J. G. Lechón, J. B. Houston et al., “Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies,” Drug Metabolism Reviews, vol. 39, no. 1, pp. 159–234, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Malhi, M. E. Guicciardi, and G. J. Gores, “Hepatocyte death: a clear and present danger,” Physiological Reviews, vol. 90, no. 3, pp. 1165–1194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Griffin, Interactions of antiretroviral protease inhibitors with hepatic transport proteins: mechanisms of drug-induced liver injury [Ph.D. thesis], University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2012.
  16. Y. Cao, A. E. Friedman-Kien, Y. Huang et al., “CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro,” Journal of Virology, vol. 64, no. 6, pp. 2553–2559, 1990. View at Google Scholar · View at Scopus
  17. S. R. Vlahakis, A. Villasis-Keever, T. S. Gomez, G. D. Bren, and C. V. Paya, “Human immunodeficiency virus-induced apoptosis of human hepatocytes via CXCR4,” Journal of Infectious Diseases, vol. 188, no. 10, pp. 1455–1460, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Núñez, “Clinical syndromes and consequences of antiretroviral-related hepatotoxicity,” Hepatology, vol. 52, no. 3, pp. 1143–1155, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Crane, D. Iser, and S. Lewin, “Human immunodeficiency virus infection and the liver,” World Journal of Hepatology, vol. 4, no. 3, pp. 91–98, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. L. Kong, W. C. Maya, M. E. Moreno-Fernandez et al., “Low-level HIV infection of hepatocytes,” Virology Journal, vol. 9, article 157, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. R. A. Arnaout, M. A. Nowak, and D. Wodarz, “HIV-1 dynamics revisited: biphasic decay by cytotoxic T lymphocyte killing?” Proceedings of the Royal Society B: Biological Sciences, vol. 267, no. 1450, pp. 1347–1354, 2000. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Rong, M. A. Gilchrist, Z. Feng, and A. S. Perelson, “Modeling within-host {HIV}-1 dynamics and the evolution of drug resistance: trade-offs between viral enzyme function and drug susceptibility,” Journal of Theoretical Biology, vol. 247, no. 4, pp. 804–818, 2007. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  23. A. B. Gumel, X.-W. Zhang, P. N. Shivakumar, M. L. Garba, and B. M. Sahai, “A new mathematical model for assessing therapeutic strategies for HIV infection,” Journal of Theoretical Medicine, vol. 4, no. 2, pp. 147–155, 2002. View at Publisher · View at Google Scholar · View at Zentralblatt MATH · View at Scopus
  24. AIDSinfo, “Side effects of anti-hiv medications, health information for patients,” U.S. Department of Health and Human Services, http://aidsinfo.nih.gov/contentfiles/sideeffectanithivmeds_cbrochure_en.pdf.
  25. B. Sharma, “Anti-HIV-1 drug toxicity and management strategies,” Neurobehavioral HIV Medicine, vol. 3, no. 1, pp. 27–40, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. A. S. Perelson and S. G. Deeks, “Drug effectiveness explained: the mathematics of antiviral agents for HIV,” Science Translational Medicine, vol. 3, no. 91, Article ID 91ps30, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. W. Lin, G. Wu, S. Li et al., “HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NF κB,” The Journal of Biological Chemistry, vol. 286, no. 4, pp. 2665–2674, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Shen, S. A. Rabi, A. R. Sedaghat et al., “A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs,” Science Translational Medicine, vol. 3, no. 91, Article ID 91ra63, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. O. Krakovska and L. M. Wahl, “Optimal drug treatment regimens for HIV depend on adherence,” Journal of Theoretical Biology, vol. 246, no. 3, pp. 499–509, 2007. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  30. L. Shen, S. Peterson, A. R. Sedaghat et al., “Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs,” Nature Medicine, vol. 14, no. 7, pp. 762–766, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. J. van der Lugt and A. Avihingsanon, “Clinical pharmacology and pharmacokinetics of antiretrovirals in Asia,” Asian Biomedicine, vol. 3, no. 1, pp. 53–62, 2009. View at Google Scholar · View at Scopus
  32. Bristol-Myers, “The electronic Medicines Compendium (eMC), Bristol-Myers Squibb Pharmaceutical Limited,” http://www.medicines.org.uk/emc/medicine/21122.
  33. L. R. Bisset, H. Lutz, J. Böni, R. Hofmann-Lehmann, R. Lüthy, and J. Schüpbach, “Combined effect of zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) antiretroviral therapy in suppressing in vitro FIV replication,” Antiviral Research, vol. 53, no. 1, pp. 35–45, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. Bristol-Myers Squibb & Gilead Sciences, “Sciences, Product monograph: Atripla (efavirenz/emtricitabine/tenofov ir disoproxil fumarate tablets) 600 mg/200 mg/300 mg antiretroviral agent,” http://www.gilead.ca/.
  35. AIDSinfo, Aidsinfo drug database, http://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/213/nel_navir-viracept-nfv.
  36. M. A. Nowak, S. Bonhoeffer, G. M. Shaw, and R. M. May, “Anti-viral drug treatment: dynamics of resistance in free virus and infected cell populations,” Journal of Theoretical Biology, vol. 184, no. 2, pp. 203–217, 1997. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Srivastava and P. Chandara, “Modeling the dynamics of HIV and CD4+ T cells during primary infection,” Nonlinear Analysis: Real World Applications, vol. 11, no. 2, pp. 612–618, 2008. View at Publisher · View at Google Scholar
  38. R. J. Smith and E. J. Schwartz, “Predicting the potential impact of a cytotoxic T-lymphocyte HIV vaccine: how often should you vaccinate and how strong should the vaccine be?” Mathematical Biosciences, vol. 212, no. 2, pp. 180–187, 2008. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  39. L. Rong and A. S. Perelson, “Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy,” PLoS Computational Biology, vol. 5, no. 10, Article ID e1000533, 18 pages, 2009. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  40. D. Wodarz and M. Nowak, “Immune responses and viral phenotype: do replication rate and cytopathogenicity inuence virus load?” Journal of Theorerical Medicine, vol. 2, pp. 113–127, 1999. View at Google Scholar
  41. S. M. Ciupe, R. M. Ribeiro, P. W. Nelson, and A. S. Perelson, “Modeling the mechanisms of acute hepatitis B virus infection,” Journal of Theoretical Biology, vol. 247, no. 1, pp. 23–35, 2007. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  42. C. Long, H. Qi, and S.-H. Huang, “Mathematical modeling of cytotoxic lymphocyte-mediated immune response to hepatitis B virus infection,” Journal of Biomedicine and Biotechnology, vol. 2008, Article ID 743690, 9 pages, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. R. J. De Boer, R. M. Ribeiro, and A. S. Perelson, “Current estimates for HIV-1 production imply rapid viral clearance in lymphoid tissues,” PLoS Computational Biology, vol. 6, no. 9, Article ID e1000906, 2010. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  44. Y. Su, Y. Wen, and L. Min, “Analysis of a HBV infection model with ALT,” in Proceedings of the IEEE 6th International Conference on Systems Biology, pp. 97–100, Xi'an, China, August 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. Z. A. Elsady, “On the solution of an HIV-immune dynamic system,” International Journal of Physical Sciences, vol. 3, no. 1, pp. 12–17, 2008. View at Google Scholar · View at Scopus
  46. R. W. King, R. M. Klabe, C. D. Reid, and S. K. Erickson-Viitanen, “Potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other human immunodeficiency virus NNRTIs, NRTIs, or protease inhibitors,” Antimicrobial Agents and Chemotherapy, vol. 46, no. 6, pp. 1640–1646, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. P. van den Driessche and J. Watmough, “Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission,” Mathematical Biosciences, vol. 180, pp. 29–48, 2002. View at Publisher · View at Google Scholar · View at Zentralblatt MATH · View at MathSciNet · View at Scopus
  48. T. B. Campbell, L. M. Smeaton, N. Kumarasamy et al., “Efficacy and safety of three antiretroviral regimen s for initial treatment of hiv- 1: a randomized clinical trial in diverse multinational settings,” PLoS Medicine, vol. 9, no. 8, Article ID e1001290, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. S.-F. Hsu Schmitz, “Effects of treatment or/and vaccination on HIV transmission in homosexuals with genetic heterogeneity,” Mathematical Biosciences, vol. 167, no. 1, pp. 1–18, 2000. View at Publisher · View at Google Scholar · View at Zentralblatt MATH · View at Scopus
  50. R. V. Culshaw, S. Ruan, and G. Webb, “A mathematical model of cell-to-cell spread of HIV-1 that includes a time delay,” Journal of Mathematical Biology, vol. 46, no. 5, pp. 425–444, 2003. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  51. B. Anderson, J. Jackson, and M. Sitharam, “Descartes' rule of signs revisited,” The American Mathematical Monthly, vol. 105, no. 5, pp. 447–451, 1998. View at Publisher · View at Google Scholar · View at Zentralblatt MATH · View at MathSciNet · View at Scopus
  52. L. Rong and A. S. Perelson, “Asymmetric division of activated latently infected cells may explain the decay kinetics of the HIV-1 latent reservoir and intermittent viral blips,” Mathematical Biosciences, vol. 217, no. 1, pp. 77–87, 2009. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  53. N. Nasr, S. Maddocks, S. G. Turville et al., “HIV-1 infection of human macrophages directly induces viperin which inhibits viral production,” Blood, vol. 120, no. 4, pp. 778–788, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. D. S. Callaway and A. S. Perelson, “HIV-1 infection and low steady state viral loads,” Bulletin of Mathematical Biology, vol. 64, no. 1, pp. 29–64, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. AIDSinfo, “Guidelines for the use of antiretroviral agents in hiv-1-infected adults and adolescents,” Department of Health and Human Services, http://aidsinfo.nih.gov/ContentFiles/Adultand AdolescentGL.pdf.
  56. W. Powderly, “Antiretroviral therapy in patients with hepatitis and HIV: weighing risks and benefits,” Clinical Infectious Diseases, vol. 38, supplement 2, pp. S109–S113, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Fisher, “Hepatotoxicity of antiretroviral therapy,” in Proceedings of the International Conference on Viral Hepatitis, New York, NY, USA, March 2013.
  58. V. Montessori, N. Press, M. Harris, L. Akagi, and J. Montaner, “Adverse e ff ects of antiretroviral therapy for hiv infection,” Canadian Medical Association or Its Licensors, vol. 170, no. 2, pp. 229–238, 2004. View at Google Scholar