Pharmacogenomics of Viral Diseases

  • Shailendra Dwivedi
  • Suraj Singh Yadav
  • Manish Kumar Singh
  • Shailja Shukla
  • Sanjay Khattri
  • Kamlesh Kumar Pant


Viral diseases are leading cause of deaths worldwide as WHO report suggests that hepatitis A virus (HAV) infects more than 80 % of the population of many developing countries. Viral hepatitis B (HBV) affects an estimated 360 million people, whereas hepatitis C affects 123 million people worldwide, and last but not least, at current, India has an HIV/AIDS population of approximately 2.4 million people and more than 30 million in whole world and now it has become a reason for 1.8 million death globally; thus, millions of people still struggle for their lives.

The progress in medical science has made it possible in overcoming the various fatal diseases such as small pox, chicken pox, dengue, etc., but human immunodeficiency viruses, influenza, and hepatitis virus have renewed challenge surprisingly. The obstacles and challenges in therapy include existence of antibiotic resistance strains of common organisms due to overuse of antibiotics, lack of vaccines, adverse drug reaction, and last but not least the susceptibility concerns. Emergence of pharmacogenomics and pharmacogenetics has shown some promises to take challenges. The discovery of human genome project has opened new vistas to understand the behaviors of genetic makeup in development and progression of diseases and treatment in various viral diseases. Current and previous decade have been engaged in making repositories of polymorphisms (SNPs) of various genes including drug-metabolizing enzymes, receptors, inflammatory cells related with immunity, and antigen-presenting cells, along with the prediction of risks. The genetic makeup alone is most likely an adequate way to handle the therapeutic decision-making process for previous regimen failure. With the introduction of new antiviral therapeutic agents, a significant improvement in progression and overall survival has been achieved, but these drugs have shown several adverse responses in some individuals, so the success is not up to the expectations. Research and acquisition of new knowledge of pharmacogenomics may help in overcoming the prevailing burden of viral diseases. So it will definitely help in selecting the most effective therapeutic agents, effective doses, and drug response for the individuals. Thus, it will be able to transform the laboratory research into the clinical bench side and will also help in understanding the pathogenesis of viral diseases with drug action, so the patients will be managed more properly and finally become able to fulfill the promise of the future.


Cervical Cancer Viral Load Nucleoside Analogue Nonnucleoside Reverse Transcriptase Inhibitor Adefovir Dipivoxil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Authors are thankful to Prof. Kamlesh K Pant, head of the department Pharmacology and Therapeutics for their proper guidance and Capt. Sudhanshu Pandey for the language editing and Mrs Shashi Dwivedi, Miss Vinita Gupta, Mr. Shobhit Srivastava, Mahendra Dwivedi, Narendra Dwivedi, Dr. Sadashiv, Virendra Saini, Durgesh, and Ram Swarup for their hearty support.


  1. Abo R et al (2012) Merging pharmacometabolomics with pharmacogenomics using ‘1000 Genomes’ single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics. Pharmacogenet Genomics 22:247–253PubMedCentralPubMedGoogle Scholar
  2. Alter MJ, Kruszon-Moran D, Nainan OV et al (1999) The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 341:556–562PubMedGoogle Scholar
  3. Altman MD et al (2008) HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants. J Am Chem Soc 130(19):6099–6113PubMedCentralPubMedGoogle Scholar
  4. Ank N, Paludan SR (2009) Type III IFNs: new layers of complexity in innate antiviral immunity. Biofactors 35(1):82–87PubMedGoogle Scholar
  5. Ank N, West H, Bartholdy C et al (2006) Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80(9):4501–4509PubMedCentralPubMedGoogle Scholar
  6. Ank N, Iversen MB, Bartholdy C et al (2008) An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. J Immunol 180(4):2474–2485PubMedGoogle Scholar
  7. Arbuthnot P, Capovilla A, Kew M (2000) Putative role of hepatitis B virus X protein in hepatocarcinogenesis: effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. J Gastroenterol Hepatol 15:357–368PubMedGoogle Scholar
  8. Australian Census (2001) Total population.!OpenDocument#Census Counts. Accessed 25 July 25 2005Google Scholar
  9. Back NK, Nijhuis M, Keulen W et al (1996) Reduced replication of 3TC-resistant HIV-1variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J 15:4040–4049PubMedCentralPubMedGoogle Scholar
  10. Barbour JD, Wrin T, Grant RM et al (2002) Evolution of phenotypic drug susceptibility and viral replication capacity during long term virologic failure of protease inhibitor therapy in human immunodeficiency virus infected adults. J Virol 76:11104–11112PubMedCentralPubMedGoogle Scholar
  11. Bartlett JA et al (2001) Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS 15(11):1369–1377PubMedGoogle Scholar
  12. Bertoletti A, Ferrari C, Fiaccadori F et al (1991) HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci USA 88:10445–10449PubMedCentralPubMedGoogle Scholar
  13. Bleiber G, Munoz M, Ciuffi A, Meylan P, Telenti A (2001) Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1. J Virol 75:3291–3300PubMedCentralPubMedGoogle Scholar
  14. Blum RA (2005) HIV resistance testing in the USA – a model for the application of pharmacogenomics in the clinical setting. Pharmacogenomics 06: future medicine. Web.
  15. Borroto-Esoda K, Harris J, Waters J et al (2004) Baseline genotype as a predictor of virological failure in patients receiving emtricitabine once daily or stavudine twice daily in combination with didanosine and efavirenz [Abstract 672]. In: 11th conference on retroviruses and opportunistic infections, San FranciscoGoogle Scholar
  16. Boucher CA, Cammack N, Schipper P et al (1993) High-level resistance to (¡) enantiomeric2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 37:2231–2234PubMedCentralPubMedGoogle Scholar
  17. Brumme Z, Dong W, Chan K, Hogg R et al (2003) Influence of polymorphisms within the CX3CR1 and MDR-1 genes on initial antiretroviral therapy response. AIDS 17:201–208PubMedGoogle Scholar
  18. Campbell TB, Young RK, Johnson SC et al (2003) Antiviral activity of lamivudine in persons infected with HIV-1 that has M184V and multiple thymidine analogue mutations [Abstract 140]. In: 12th international HIV drug resistance workshop, Los CabosGoogle Scholar
  19. Carman WF (1996) Molecular variants of hepatitis B virus. Clin Lab Med 16:407–428PubMedGoogle Scholar
  20. Carman WF, Jacyna MR, Hadziyannis S et al (1989) Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 2:588–591PubMedGoogle Scholar
  21. Carman WF, Zanetti AR, Karayiannis P et al (1990) Vaccine-induced escape mutant of hepatitis B virus. Lancet 336:325–329PubMedGoogle Scholar
  22. Carrington M, Wang S, Martin MP, Gao X, Schiffman M et al (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med 201:1069–1075PubMedCentralPubMedGoogle Scholar
  23. Chamberlain PP, Ren J, Nichols CE et al (2002) Crystal structures of zidovudine- or lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215. J Virol 76:10015–10019PubMedCentralPubMedGoogle Scholar
  24. Chander G, Sulkowski MS, Jenckes MW et al (2002) Treatment of chronic hepatitis C: a systematic review. Hepatology 36(Suppl):S135–S144PubMedGoogle Scholar
  25. Chantarangsu S (2009) A CYP2B6 haplotype influences NVP plasma concentrations postpartum following a single intrapartum dose for the prevention of mother to child transmission of HIV in Thai women [Abstract O-02]. In: 10th international workshop on HIV clinical pharmacology, Amsterdam, 15–17 Apr 2009Google Scholar
  26. Chayama K, Suzuki Y, Kobayashi M et al (1998) Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy. Hepatology 27(6):1711–1716PubMedGoogle Scholar
  27. Chellappan S et al (2007) Design of mutation-resistant HIV protease inhibitors with the substrate envelope hypothesis. Chem Biol Drug Des 69(5):298–313PubMedGoogle Scholar
  28. Chowdhury A, Santra A, Chaudhuri S et al (2003) Hepatitis C virus infection in the general population: a community-based study in West Bengal, India. Hepatology 37:802–809PubMedGoogle Scholar
  29. Czene K, Lichtenstein P, Hemminki K (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer 99:260–266PubMedGoogle Scholar
  30. D’Arminio Monforte A, Lepri AC, Rezza G (2000) Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients. AIDS 14:499–507PubMedGoogle Scholar
  31. Daly AK (2010) Genome-wide association studies in pharmacogenomics. Nat Rev Genet 11:241–246PubMedGoogle Scholar
  32. De Clercq E (2004) Antivirals and antiviral strategies. Nat Rev Microbiol 2:704–720PubMedGoogle Scholar
  33. Deeks SG, Wrin T, Liegler T et al (2001) Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med 344:472–480PubMedGoogle Scholar
  34. Deeks SG, Martin JN, Hoh R et al (2003) Continued reverse transcriptase inhibitor therapy is sufficient to maintain short-term partial suppression of multi-drug resistant viremia [Abstract 640]. In: 10th conference on retroviruses and opportunistic infections, BostonGoogle Scholar
  35. Dellgren C, Gad HH, Hamming OJ, Melchjorsen J, Hartmann R (2009) Human interferon-lambda3 is a potent member of the type III interferon family. Genes Immun 10(2):125–131PubMedGoogle Scholar
  36. Derdeyn CA, Decker JM, Sfakianos JN et al (2001) Sensitivity of human immunodeficiency virus type 1 to fusion inhibitors targeted to the gp41 first heptad repeat involves distinct regions of gp41 and is consistently modulated by gp120 interactions with the coreceptor. J Virol 75:8605–8614PubMedCentralPubMedGoogle Scholar
  37. Desenclos JC (2000) Epidemiology of hepatitis C. Revue du Praticien 50:1066–1070PubMedGoogle Scholar
  38. Doyle SE, Schreckhise H, Khuu-Duong K et al (2006) Interleukin-29 uses a type 1 interferon- like program to promote antiviral responses in human hepatocytes. Hepatology 44:896–906PubMedGoogle Scholar
  39. Dragsted U, Fox Z, Mathiesen L et al (2004) Final week 48 analysis of a phase 4, randomised, open-label, multi-center trial to evaluate safety and efficacy of continued lamivudine twice daily versus discontinuation of lamivudine in HIV-1-infected adults with virological failure on ongoing combination treatments containing lamivudine: the COLATE trial [Abstract 549]. In: 11th conference on retroviruses and opportunistic infections, San FranciscoGoogle Scholar
  40. Dulioust A, Paulous S, Guillemot L, Delavalle AM, Boue F, Clavel F (1999) Constrained evolution of human immunodeficiency virus type 1 protease during sequential therapy with two distinct protease inhibitors. J Virol 73:850–854PubMedCentralPubMedGoogle Scholar
  41. Durbin RM et al (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061–1073PubMedGoogle Scholar
  42. Dykxhoorn DM, Lieberman J (2006) Silencing viral infection. PLoS Med 3:1000–1004Google Scholar
  43. Esnouf RM, Ren J, Hopkins AL et al (1997) Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP)U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc Natl Acad Sci USA 94:3984–3989PubMedCentralPubMedGoogle Scholar
  44. Farci P, Purcell RH (2000) Clinical significance of hepatitis C virus genotypes and quasispecies. Semin Liver Dis 20:103–126PubMedGoogle Scholar
  45. Feeney ME, Tang Y, Pfafferott K et al (2005) HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response. J Immunol 174(12):7524–7530PubMedGoogle Scholar
  46. Ferrantelli F, Rasmussen RA, Hofmann-Lehmann R et al (2002) Do not underestimate the power of antibodies—lessons from adoptive transfer of antibodies against HIV. Vaccine 20(suppl 4):A61–A65PubMedGoogle Scholar
  47. Fukuda R, Ishimura N, Kushiyama Y et al (1996) Hepatitis B virus with X gene mutation is associated with the majority of serologically silent non-B, non-C chronic hepatitis. Microbiol Immunol 40:481–488PubMedGoogle Scholar
  48. Gallant JE, Rodriguez AE, Weinberg W et al (2003) Early non-response to tenofovir DF (TDF) + abacavir (ABC) and lamivudine (3TC) in a randomized trial compared to efavirenz (EFV) + ABC and 3TC: ESS30009[Abstract 1722a]. In: 43rd interscience conference on antimicrobial agents and chemotherapy, ChicagoGoogle Scholar
  49. Gallo RC (2005) The end or the beginning of the drive to an HIV preventive vaccine: a view from over 20 years. Lancet 366(9500):1894–1898PubMedGoogle Scholar
  50. Ge D, Fellay J, Thompson AJ et al (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401PubMedGoogle Scholar
  51. Girard M, Meignier B, Barre-Sinoussi F et al (1995) Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1. J Virol 69(10):6239–6248PubMedCentralPubMedGoogle Scholar
  52. Haagmans BL, Andeweg AC, Osterhaus A (2009) The application of genomics to emerging zoonotic viral diseases. PLoS Pathog 5(10):e1000557PubMedCentralPubMedGoogle Scholar
  53. Haas D, Ribaudo H, Kim R et al (2004) Pharmacogenetics of efavirenz and central nervous system side effects. AIDS 18:2391–2400PubMedGoogle Scholar
  54. Hanna GJ, D’Aquila RT (2001) Clinical use of genotypic and phenotypic drug resistance testing to monitor antiretroviral chemotherapy. Clin Infect Dis 32:774–782PubMedGoogle Scholar
  55. Hanna GJ, Johnson VA, Kuritzkes DR et al (2000) Patterns of resistance mutations selected by treatment of human immunodeficiency virus type 1 infection with zidovudine, didanosine, and nevirapine. J Infect Dis 181:904–911PubMedGoogle Scholar
  56. Harro C et al (2009) Safety and immunogenicity of the Merck adenovirus serotype 5 (MRKAd5) and MRKAd6 human immunodeficiency virus type 1 trigene vaccines alone and in combination in healthy adults. Clin Vaccine Immunol 16:1285–1292PubMedCentralPubMedGoogle Scholar
  57. Havlir DV, Hellmann NS, Petropoulos CJ et al (2000) Drug susceptibility in HIV infection after viral rebound in patients receiving indinavir-containing regimens. JAMA 283:229–234PubMedGoogle Scholar
  58. Hemminki K, Chen B (1999) Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol Biomarkers Prev 15:1413–1414Google Scholar
  59. Hemminki K, Dong C, Vaittinen P (2006) Familial risks in cervical cancer: is there a hereditary component? Int J Cancer 82:775–781Google Scholar
  60. Hijikata M, Mishiro S, Miyamoto C et al (2001) Genetic polymorphism of the MxA gene promoter and interferon responsiveness of hepatitis C patients: revisited by analyzing two SNP sites (−123 and −88) in vivo and in vitro. Intervirology 44(6):379–382PubMedGoogle Scholar
  61. Hildesheim A, Wang SS (2002) Host and viral genetics and risk of cervical cancer: a review. Virus Res 89:229–240PubMedGoogle Scholar
  62. Hirsch MS et al (2000) Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA panel. J Am Med Assoc 283:2417–2426Google Scholar
  63. Hirsch MS, Günthard HF, Schapiro JM et al (2008) Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 47:266–285PubMedGoogle Scholar
  64. Höhler T, Kruger A, Gerken G et al (1998a) Tumor necrosis factor alpha promoter polymorphism at position –238 is associated with chronic active hepatitis C infection. J Med Virol 54:173–177PubMedGoogle Scholar
  65. Höhler T, Kruger A, Gerken G et al (1998b) A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis B infection. Clin Exp Immunol 111(3):579–582PubMedCentralPubMedGoogle Scholar
  66. Hong L et al (2000) Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: insights into the mechanisms of drug resistance. Protein Sci 9:1898–1904PubMedCentralPubMedGoogle Scholar
  67. Hoofnagle JH, di Bisceglie AM (1997) The treatment of chronic viral hepatitis. N Engl J Med 336(5):347–356PubMedGoogle Scholar
  68. Hsiou Y, Ding J, Das K et al (2001) The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. J Mol Biol 309:437–445PubMedGoogle Scholar
  69. Hsu HY, Chang MH, Ni Y-H, Lin HH, Wang SM, Chen DS (1997) Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis. Hepatology 26:786–791PubMedGoogle Scholar
  70. Hu ZX et al (2004) Fitness of T215Y vs T215F mutants in HIV-1 RT: comparison of specific thymidine analogue-resistance mutation patterns [Abstract 638]. In: 11th conference on retroviruses and opportunistic infections, San FranciscoGoogle Scholar
  71. Hussain SK, Sundquist J, Hemminki K (2008) Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database. Int J Cancer 122:1873–1878PubMedGoogle Scholar
  72. Hutnick NA et al (2010) Adenovirus-specific human T cells are pervasive, polyfunctional, and cross-reactive. Vaccine 28:1932–1941PubMedCentralPubMedGoogle Scholar
  73. International AIDS Society-USA (2002) HIV drug resistance mutations, San Francisco. Accessed 9 Feb 2004
  74. Iversen AK, Shafer RW, Wehrly K et al (1996) Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J Virol 70:1086–1090PubMedCentralPubMedGoogle Scholar
  75. Izzedine H, Hulot J, Villard E (2006) Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J Infect Dis 194:1481–1491PubMedGoogle Scholar
  76. Kahn JA (2009) HPV vaccination for the prevention of cervical intraepithelial neoplasia. N Engl J Med 361(3):271–278PubMedGoogle Scholar
  77. Kao JH, Wu NH, Chen PJ et al (2000) Hepatitis B genotypes and the response to interferon therapy. J Hepatol 33:998–1002PubMedGoogle Scholar
  78. Kao JH, Chen PJ, Lai MY et al (2002) Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 40:1207–1209PubMedCentralPubMedGoogle Scholar
  79. Kaufmann D, Pantaleo G, Sudre P, Telenti A (1998) CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART): Swiss HIV Cohort Study. Lancet 351:723–724PubMedGoogle Scholar
  80. Kilby JM, Eron JJ (2003) Novel therapies based on mechanisms of HIV-1 cell entry. N Engl J Med 348:2228–2238PubMedGoogle Scholar
  81. King JK, Yeh SH, Lin MW et al (2002) Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients: a pilot study. Hepatology 36:1416–1424PubMedGoogle Scholar
  82. Klein TE et al (2009) Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 360:753–764PubMedGoogle Scholar
  83. Kohl NE et al (1988) Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci USA 85(13):4686–4690PubMedCentralPubMedGoogle Scholar
  84. Kosalaraksa P, Kavlick MF, Maroun V, Le R, Mitsuya H (1999) Comparative fitness of multidideoxynucleoside-resistant human immunodeficiency virus type 1 (HIV-1) in an in vitro competitive HIV-1 replication assay. J Virol 73:5356–5363PubMedCentralPubMedGoogle Scholar
  85. Kramvis A, Kew MC (1999) The core promoter of hepatitis B virus. J Viral Hepat 6:415–427PubMedGoogle Scholar
  86. Kramvis A, Bukofzer S, Kew MC, Song E (1997) Nucleic acid sequence analysis of the precore region of the hepatitis B virus from sera of southern African black adult carriers of the virus. Hepatology 25:235–240PubMedGoogle Scholar
  87. Kuritzkes DR (2004) Quantification of human immunodeficiency virus type 1 by reverse transcriptase-coupled polymerase chain reaction. J Infect Dis 190(11):2047–2054Google Scholar
  88. Lankisch T, Moebius UM, Wehmeier M (2006) Gilbert’s disease and atazanavir: from phenotype to UDP glucuronosyltransferase haplotype. Hepatology 44:1324–1332PubMedGoogle Scholar
  89. Larder BA, Kemp SD (1989) Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246:1155–1158PubMedGoogle Scholar
  90. Larder BA, Kemp SD, Harrigan PR (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269:696–699PubMedGoogle Scholar
  91. Lau DT et al (1997) Long-term follow-up of patients with chronic hepatitis B treated with interferon alpha. Gastroenterology 113(5):1660–1667PubMedGoogle Scholar
  92. Law MG, Dore GJ, Bath N et al (2003) Modeling hepatitis C virus incidence, prevalence, and long-term sequelae in Australia. Int J Epidemiol 32:717–724PubMedGoogle Scholar
  93. Lee WM (1997) Hepatitis B virus infection. N Engl J Med 337(24):1733–1745PubMedGoogle Scholar
  94. Lee YI, Hur GM, Suh DJ, Kim SH (1996) Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants. J Gen Virol 77:1129–1138PubMedGoogle Scholar
  95. Lefebvre E, Schiffer CA (2008) Resilience to resistance of HIV-1 protease inhibitors: profile of darunavir. AIDS Rev 10(3):131–142PubMedCentralPubMedGoogle Scholar
  96. Lemon SM (1994) Hepatitis A virus. In: Webster RG, Granoff A (eds) Encyclopedia of virology. Academic Press Ltd., London, pp 546–554Google Scholar
  97. Liapakis A, Jacobson I (2010) Pharmacogenetics of hepatitis C therapy. Pharmacogenomics 11(2):135–139PubMedGoogle Scholar
  98. Liaw YF (2002) Therapy of chronic hepatitis B: current challenges and opportunities. J Viral Hepat 9:393–399PubMedGoogle Scholar
  99. Lin C (2006) HCV NS3-4A Serine Protease: Hepatitis C Viruses: Genomes and Molecular Biology. Norfolk (UK): Horizon Biosci. PMID: 21250386Google Scholar
  100. Ling R, Mutimer D, Ahmed M et al (1996) Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine. Hepatology 24:711–713PubMedGoogle Scholar
  101. Little SJ, KK Koelsch, Ignacio CC et al (2004) Persistence of transmitted drug-resistant virus among patients with primary HIV infection deferring antiretroviral therapy [Abstract 36LB]. In: 11th conference on retroviruses and opportunistic infections, San FranciscoGoogle Scholar
  102. Lok AS (2002) Chronic hepatitis B. N Engl J Med 346(22):1682–1683PubMedGoogle Scholar
  103. Mahoney FJ (1999) Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev 12(2):351–366PubMedCentralPubMedGoogle Scholar
  104. Malhotra U et al (2001) Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment. J Clin Invest 107:505–517PubMedCentralPubMedGoogle Scholar
  105. Mallal S, Phillips E, Carosi G, Workman C (2008) PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358:568–657PubMedGoogle Scholar
  106. Mammano F, Petit C, Clavel F (1998) Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 72:7632–7637PubMedCentralPubMedGoogle Scholar
  107. Mammano F, Trouplin V, Zennou V, Clavel F (2000) Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug. J Virol 74:8524–8531PubMedCentralPubMedGoogle Scholar
  108. Marcellin P, Castelnau C, Boyer N (2002) Treatment of hepatitis B. Rev Med Interne 23(S5):535s–536sPubMedGoogle Scholar
  109. Marcello T, Grakoui A, Barba-Spaeth G et al (2006) Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131:1887–1898PubMedGoogle Scholar
  110. Maruyama T, Kuwata S, Koike K et al (1998) Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: no association between genome conversion and seroconversion. Hepatology 27:245–253PubMedGoogle Scholar
  111. Mascola JR, Snyder SW, Weislow OS et al (1996) Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. J Infect Dis 173(2):340–348PubMedGoogle Scholar
  112. Mc Cutchan FE, Hoelscher M, Tovanabutra S et al (2005) In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months post infection. J Virol 79(18):11693–11704Google Scholar
  113. McHutchison JG, Gordon SC, Schiff ER et al (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 339:1485–1492PubMedGoogle Scholar
  114. McMichael A, Hanke T (2002) The quest for an AIDS vaccine: is the CD8+ T-cell approach feasible? Nat Rev Immunol 2(4):283–291PubMedGoogle Scholar
  115. McMichael AJ, Rowland-Jones SL (2001) Cellular immune responses to HIV. Nature 410:980–987PubMedGoogle Scholar
  116. Mehandru S et al (2004) Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 200:761–777PubMedCentralPubMedGoogle Scholar
  117. Mellors J, Palmer S, Nissley D et al (2003) Low frequency non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants contribute to failure of efavirenz-containing regimens in NNRTI-experienced patients with negative standard genotypes for NNRTI mutations [Abstract 134]. In: 12th international HIV drug resistance workshop, Los CabosGoogle Scholar
  118. Melnick JL (1995) History and epidemiology of hepatitis A virus. J Infect Dis 171(Suppl 1):S2–S8PubMedGoogle Scholar
  119. Meyer PR, Matsuura SE, Mian AM, So AG, Scott WA (1999) A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol Cell 4:35–43PubMedGoogle Scholar
  120. Molla A, Korneyeva M, Gao Q et al (1996) Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 2:760–766PubMedGoogle Scholar
  121. Murphy DG, Cote L, Fauvel M, Rene P, Vincelette J (2000) Multicenter comparison of Roche COBAS AMPLICOR MONITOR version 1.5, Organon Teknika NucliSens QT with Extractor and Bayer Quantiplex version 3.0 for quantification of human Immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 38:4034–4041PubMedCentralPubMedGoogle Scholar
  122. Nalam MN, Schiffer CA (2008) New approaches to HIV protease inhibitor drug design II: testing the substrate envelope hypothesis to avoid drug resistance and discover robust inhibitors. Curr Opin HIV AIDS 3(6):642–646PubMedCentralPubMedGoogle Scholar
  123. Nijhuis M, Schuurman R, de Jong D et al (1999) Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 13:2349–2359PubMedGoogle Scholar
  124. Ohshima S, Komatsu M, Nakane K et al (2000) Iatrogenic GB virus C/hepatitis G virus infection in an area endemic for hepatitis C virus. J Hosp Infect 44:179–185PubMedGoogle Scholar
  125. Okamoto H, Tsuda F, Akahane Y et al (1994) Hepatitis B virus with mutations in the core of the promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. J Virol 68:8102–8110PubMedCentralPubMedGoogle Scholar
  126. Ono-Nita SK, Kato N, Shiratori Y et al (1999) Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors. J Clin Invest 103:1635–1640PubMedCentralPubMedGoogle Scholar
  127. Pagliaccetti NE, Eduardo R, Kleinstein SH et al (2008) Interleukin-29 functions cooperatively with interferon to induce antiviral gene expression and inhibit hepatitis C virus replication. J Biol Chem 283(44):30079–30089PubMedCentralPubMedGoogle Scholar
  128. Palitzsch KD, Hottentrager B, Schlottmann K et al (1999) Prevalence of antibodies against hepatitis C virus in the adult German population. Eur J Gastroenterol Hepatol 11:1215–1220PubMedGoogle Scholar
  129. Peet NP (2010) Drug resistance: a growing problem. Drug Discov Today 15(15–16):583–586PubMedGoogle Scholar
  130. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271(5255):1582–1586PubMedGoogle Scholar
  131. Perz JF, Farrington LA, Pecoraro C, Hutin YJF, Armstrong GL (2004) Estimated global prevalence of hepatitis C virus infection. In: 42nd annual meeting of the Infectious Diseases Society of America, Boston, 30 Sept–3 Oct 2004Google Scholar
  132. Peterlin BM, Trono D (2003) Hide, shield and strike back: how HIV-infected cells avoid immune eradication. Nat Rev Immunol 23(2):97–107Google Scholar
  133. Picard V, Angelini E, Maillard A et al (2001) Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. J Infect Dis 184:781–784PubMedGoogle Scholar
  134. Pichoud C, Seigne`res B, Wang Z, Trepo C, Zoulim F (1999) Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance. Hepatology 29:230–237PubMedGoogle Scholar
  135. Pirmohamed M (2001) The pharmacogenomics of HIV therapy. Pharmacogenomics J 1:243–253. Web.
  136. Population Reference Bureau (2004) World population datasheet Accessed 25 July 2005
  137. Prabu-Jeyabalan M, King N, Nalivaika E, Scott W, Schiffer C (2002) Drug resistance and substrate recognition in HIV-1 protease. Antivir Ther 7(Suppl 1):S36, abstractGoogle Scholar
  138. Ramsey LB et al (2012) Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 22:1–8PubMedCentralPubMedGoogle Scholar
  139. Rauch A, Kutalik Z, Descombes P et al (2010) Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genomewide association study. Gastroenterology 138:1338–1345PubMedGoogle Scholar
  140. Reeves JD, Gallo SA, Ahmad N et al (2002) Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci USA 99:16249–16254PubMedCentralPubMedGoogle Scholar
  141. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361:2209–2220PubMedGoogle Scholar
  142. Richman DD (1990) Susceptibility to nucleoside analogues of zidovudine-resistant isolates of human immunodeficiency virus. Am J Med 88:8S–10SPubMedGoogle Scholar
  143. Rimsky LT, Shugars DC, Matthews TJ (1998) Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 72:986–993PubMedCentralPubMedGoogle Scholar
  144. Roberts NA, Martin JA, Kinchington D et al (1990) Rational design of peptide-based HIV proteinase inhibitors. Science 248:358–361PubMedGoogle Scholar
  145. Ross L, Johnson M, DeMasi R et al (2000) Viral genetic heterogeneity in HIV-1-infected individuals is associated with increasing use of HAART and higher viremia. AIDS 14:813–819PubMedGoogle Scholar
  146. Safaeian M, Hildesheim A, Gonzalez P, Yu K, Porras C et al (2012) Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLoS One 7(4):e33619. doi: 10.1371/journal.pone.0033619 PubMedCentralPubMedGoogle Scholar
  147. Sagreiya H et al (2010) Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9. Pharmacogenet Genomics 20:407–413PubMedGoogle Scholar
  148. Salemi, M (2004) HIVbase: a PC/Windows-based software offering storage and querying power for locally held HIV-1 genetic, experimental and clinical data. Oxford J Bioinform 20(3): 436–438. Web.
  149. Sarafianos SG, Das K, Clark AD Jr et al (1999) Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc Natl Acad Sci USA 96:10027–10032PubMedCentralPubMedGoogle Scholar
  150. Schapiro JM, Winters MA, Lawrence J, Merigan TC (1999) Clinical cross-resistance between the HIV-1 protease inhibitors saquinavir and indinavir and correlations with genotypic mutations. AIDS 13:359–365PubMedGoogle Scholar
  151. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007) Human papillomavirus and cervical cancer. Lancet 370:890–907PubMedGoogle Scholar
  152. Schuurman R, Nijhuis M, van Leeuwen R et al (1995) Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis 171:1411–1419PubMedGoogle Scholar
  153. Shafer, R (2003) Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res 31:1298–1303. Web. 08 Dec 2011.
  154. Shapiro CN, Margolis HS (1993) Worldwide epidemiology of hepatitis A virus infection. J Hepatol 18(Suppl 2):S11–S14PubMedGoogle Scholar
  155. Shenderovich MD, Kagan RM, Heseltine PN, Ramnarayan K (2003) Structure-based phenotyping predicts HIV-1 protease inhibitor resistance. Protein Sci 12(8):1706–1718PubMedCentralPubMedGoogle Scholar
  156. Simek MD et al (2009) Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high through put neutralization assay together with an analytical selection algorithm. J Virol 83:7337–7348PubMedCentralPubMedGoogle Scholar
  157. Squires K, Young B, Patel P et al (2008) First large, multicenter, open label study utilizing HLA-B*5701 screening for abacavir hypersensitivity in North America. AIDS 22:1673–1675PubMedGoogle Scholar
  158. Stevens W, Horsfield P, Scott LE (2007) Evaluation of the performance of the automated NucliSENS EasyMAG and EasyQ systems versus the Roche AmpliPrep-AMPLICOR combination for high-throughput monitoring of human immunodeficiency virus Load. J Clin Microbiol 45:1244–1249PubMedCentralPubMedGoogle Scholar
  159. Suppiah V, Moldovan M, Ahlenstiel G et al (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41(10):1100–1104PubMedGoogle Scholar
  160. Tanaka Y, Nishida N, Sugiyama M et al (2009) Genome-wide association of IL28B with response to pegylated interferon-a and ribavirin therapy for chronic hepatitis C. Nat Genet 10:1105–1111Google Scholar
  161. Thio CL, Thomas DL (2010) Interleukin-28b: a key piece of the hepatitis C virus recovery puzzle. Gastroenterology 138(4):1240–1243PubMedCentralPubMedGoogle Scholar
  162. Thursz MR, Thomas HC (1997) Host factors in chronic viral hepatitis. Semin Liver Dis 17:345–350PubMedGoogle Scholar
  163. Torti C, Lapadula G, Maggiolo F et al (2007) Predictors of AIDS defining events among advanced naïve patients after HAART. HIV Clin Trials 8:112–120PubMedGoogle Scholar
  164. Trautmann L et al (2006) Upregulation of PD-1 expression on HIV-specific CD8+T cells leads to reversible immune dysfunction. Nat Med 12:1198–1202PubMedGoogle Scholar
  165. Twyman RM (2004) SNP discovery and typing technologies for pharmacogenomics. Curr Top Med Chem 4(13):1423–1431PubMedGoogle Scholar
  166. Van Gils MJ et al (2010) High prevalence of neutralizing activity against multiple unrelated human immunodeficiency virus type 1 (HIV-1) subtype B variants in sera from HIV-1 subtype B-infected individuals: evidence for subtype specific rather than strain-specific neutralizing activity. J Gen Virol 91(Part 1):250–258PubMedCentralPubMedGoogle Scholar
  167. Verkoczy L et al (2010) Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance. Proc Natl Acad Sci USA 107:181–186PubMedCentralPubMedGoogle Scholar
  168. Viral Hepatitis Prevention Board (1997) News from the VHPB meeting in St. Julians, Malta. Viral Hepatitis 6.
  169. Wedemeyer H, Schuller E, Schlaphoff V, Stauber RE, Wiegand J, Schiefke I, Firbas C, Jilma B, Thursz M, Zeuzem S, Hofmann WP, Hinrichsen H, Tauber E, Manns MP, Klade CS (2009) Therapeutic vaccine IC41 as late add-on to standard treatment in patients with chronic hepatitis C. Vaccine 27(37):5142–5151. doi: 10.1016/j.vaccine.2009.06.027 PubMedGoogle Scholar
  170. Wei X, Decker JM, Wang S et al (2003) Antibody neutralization and escape by HIV-1. Nature 422(6929):307–312PubMedGoogle Scholar
  171. Weinshilboum RM, Sladek SL (1980) Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32:651–662PubMedCentralPubMedGoogle Scholar
  172. Weinstein C et al (2001) Use of genotypic resistance testing to guide hiv therapy: clinical impact and cost-effectiveness. Ann Intern Med 134:440–450PubMedGoogle Scholar
  173. Welzel TM, Morgan TR, Bonkovsky HL et al (2009) Variants in interferon alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial. Hepatology 49(6):1847–1858PubMedCentralPubMedGoogle Scholar
  174. World Health Organization (1997) The world health report.3. World Health Organization, GenevaGoogle Scholar
  175. World Health Organization (2000) Hepatitis B. World Health Organization fact sheet 204. WHO 4 Web.
  176. Wu TD et al (2003) Mutation patterns and structural correlates in human immunodeficiency virus type 1 protease following different protease inhibitor treatments. J Virol 77(8):4836–4847PubMedCentralPubMedGoogle Scholar
  177. Xia GL, Liu CB, Cao HL et al (1996) Prevalence of hepatitis B and C virus infections in the general Chinese population: results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D, and E virus infections in China, 1992. Int Hepatol Commun 5:62–73Google Scholar
  178. Yang X, Tomov V, Kurteva S et al (2004) Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1. J Virol 78(23):12975–12986PubMedCentralPubMedGoogle Scholar
  179. Yee LJ, Tang J, Gibson AW et al (2001) Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection. Hepatology 33:708–712PubMedGoogle Scholar
  180. Yuan TT, Lin MH, Qiu SM, Shih C (1998) Functional characterization of naturally occurring variants of human hepatitis B virus containing the core internal deletion mutation. J Virol 72:2168–2176PubMedCentralPubMedGoogle Scholar
  181. Zennou V, Mammano F, Paulous S, Mathez D, Clavel F (1998) Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects in human immunodeficiency virus type 1 variants selected for resistance to protease inhibitors in vivo. J Virol 72:3300–3306PubMedCentralPubMedGoogle Scholar
  182. Zou S, Tepper M, El Saadany S (2000) Prediction of hepatitis C burden in Canada. Can J Gastroenterol 14:575–580PubMedGoogle Scholar

Copyright information

© Springer India 2013

Authors and Affiliations

  • Shailendra Dwivedi
    • 1
  • Suraj Singh Yadav
    • 1
  • Manish Kumar Singh
    • 1
  • Shailja Shukla
    • 1
  • Sanjay Khattri
    • 1
  • Kamlesh Kumar Pant
    • 1
  1. 1.Department of Pharmacology and TherapeuticsCSM Medical University, Erstwhile-King George Medical CollegeLucknowIndia

Personalised recommendations