Antiviral strategies to combat cytomegalovirus infections in transplant recipients

Current Opinion in Pharmacology

Volumn 8, Issue 5, 2008, Pages 541-548

  Lischka, Peter ^a   Zimmermann, Holger ^a  

^a AiCuris GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; ANTIVIRUS AGENT; ARTESUNATE; BENZIMIDAVIR; CAMVIA; CIDOFOVIR; CMX 001; ENZYME INHIBITOR; FOMIVIRSEN; FOSCARNET SODIUM; GANCICLOVIR; GW 275175X; NUCLEOSIDE ANALOG; PLACEBO; T 0902611; T 611; TERMINASE INHIBITOR; TOMEGLOVIR; UNCLASSIFIED DRUG; VALACICLOVIR; VALGANCICLOVIR;

ANEMIA; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; BONE MARROW TRANSPLANTATION; CARCINOGENICITY; CLINICAL TRIAL; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; DRUG ABSORPTION; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG MARKETING; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; EYE INFLAMMATION; HERPES SIMPLEX; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INCIDENCE; INFECTION PREVENTION; INTRAOCULAR PRESSURE; KIDNEY DISEASE; MORBIDITY; MORTALITY; NEPHROTOXICITY; NEUTROPENIA; NONHUMAN; ORGAN TRANSPLANTATION; PATHOGENESIS; PRIORITY JOURNAL; RECIPIENT; REPRODUCTIVE TOXICITY; RETINITIS; REVIEW; SIDE EFFECT; TERATOGENICITY; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; VIRUS REPLICATION;

ANIMALS; ANTIVIRAL AGENTS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; DRUG RESISTANCE, VIRAL; HUMANS; ORGAN TRANSPLANTATION;

EID: 54849431773     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2008.07.002     Document Type: Review

References (53)

1. Gandhi M.K., and Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 4 (2004) 725-738
2. Andrei G., De C.E., and Snoeck R. Novel inhibitors of human CMV. Curr Opin Investig Drugs 9 (2008) 132-145. Comprehensive overview of approaches to generate novel anti-CMV drugs.
3. Sia I.G., and Patel R. New strategies for prevention and therapy of cytomegalovirus infection and disease in solid-organ transplant recipients. Clin Microbiol Rev 13 (2000) 83-121 table
4. Singh N. Cytomegalovirus infection in solid organ transplant recipients: new challenges and their implications for preventive strategies. J Clin Virol 35 (2006) 474-477
5. Singh N., and Wagener M.M. Strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 144 (2006) 456-457
6. Sing G.K., and Ruscetti F.W. The role of human cytomegalovirus in haematological diseases. Baillieres Clin Haematol 8 (1995) 149-163
7. Gandhi M.K., Wills M.R., Sissons J.G., and Carmichael A.J. Human cytomegalovirus-specific immunity following haemopoietic stem cell transplantation. Blood Rev 17 (2003) 259-264
8. Freeman R.B., Paya C., Pescovitz M.D., Humar A., Dominguez E., Washburn K., Blumberg E., Alexander B., and Heaton N. Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients. Transplantation 78 (2004) 1765-1773
9. Ljungman P., Perez-Bercoff L., Jonsson J., Avetisyan G., Sparrelid E., Aschan J., Barkholt L., Larsson K., Winiarski J., Yun Z., and Ringden O. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica 91 (2006) 78-83
10. Biron K.K. Antiviral drugs for cytomegalovirus diseases. Antiviral Res 71 (2006) 154-163
11. Wiltshire H., Hirankarn S., Farrell C., Paya C., Pescovitz M.D., Humar A., Dominguez E., Washburn K., Blumberg E., Alexander B., et al. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet 44 (2005) 495-507
12. Wiltshire H., Paya C.V., Pescovitz M.D., Humar A., Dominguez E., Washburn K., Blumberg E., Alexander B., Freeman R., Heaton N., and Zuideveld K.P. Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation 79 (2005) 1477-1483
13. Littler E., Stuart A.D., and Chee M.S. Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature 358 (1992) 160-162
14. Sullivan V., Talarico C.L., Stanat S.C., Davis M., Coen D.M., and Biron K.K. A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature 358 (1992) 162-164
15. Steininger C. Novel therapies for cytomegalovirus disease. Recent Patents Anti-Infect Drug Disc 2 (2007) 53-72. Recent summary on HCMV treatment options and novel drugs in research and development.
16. De C.E., and Holy A. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat Rev Drug Discov 4 (2005) 928-940
17. Jacobson M.A. Treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 337 (1997) 105-114
18. Mercorelli B., Sinigalia E., Loregian A., and Palu G. Human cytomegalovirus DNA replication: antiviral targets and drugs. Rev Med Virol 18 (2007) 177-210
19. Wagstaff A.J., and Bryson H.M. Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs 48 (1994) 199-226
20. Razonable R.R., and Emery V.C. Management of CMV infection and disease in transplant patients. Herpes 11 February (2004) 77-86
21. Perry C.M., and Balfour J.A. Fomivirsen. Drugs 57 (1999) 375-380
22. Lowance D., Neumayer H.H., Legendre C.M., Squifflet J.P., Kovarik J., Brennan P.J., Norman D., Mendez R., Keating M.R., Coggon G.L., et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med 340 (1999) 1462-1470
23. Singh N. Antiviral drugs for cytomegalovirus in transplant recipients: advantages of pre-emptive therapy. Rev Med Virol 16 (2006) 281-287. Expert review compiling the current data in favour of CMV pre-emptive therapy.
24. Snydman D.R. The case for cytomegalovirus prophylaxis in solid organ transplantation. Rev Med Virol 16 (2006) 289-295. Expert review compiling the current data in favour of CMV prophylaxis therapy.
25. Rubin R.H. The indirect effects of cytomegalovirus infection on the outcome of organ transplantation. JAMA 261 (1989) 3607-3609
26. Hodson E.M., Barcley P.G., Craig J.C., Jones C., Kable K., Strippoli G.F.M., Vimalachandra D., and Webster A.C. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev 4 (2005) 1-115
27. Kliem V., Fricke L., Wollbrink T., Burg M., Radermacher J., and Rohde F. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial. Am J Transplant 8 (2008) 975-983. Latest data on a randomized placebo controlled trial comparing pre-emptive vs. prophylatic HCMV treatments in solid organ transplant patients.
28. Baldanti F., Lilleri D., and Gerna G. Human cytomegalovirus load measurement and its applications for pre-emptive therapy in patients undergoing hematopoietic stem cell transplantation. Hematol Oncol 26 (2008) 123-130
29. Baldanti F., Lilleri D., and Gerna G. Monitoring human cytomegalovirus infection in transplant recipients. J Clin Virol 41 (2008) 237-241. Expert view on the usage of increased diagnostics to limit and guide HCMV treatment describing clinical studies performed to validate thresholds for initiating pre-emptive therapy.
30. Limaye A.P., Corey L., Koelle D.M., Davis C.L., and Boeckh M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet 356 (2000) 645-649
31. Eckle T., Lang P., Prix L., Jahn G., Klingebiel T., Handgretinger R., Selle B., Niethammer D., and Hamprecht K. Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant 30 (2002) 433-439
32. Gilbert C., and Boivin G. Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother 49 (2005) 873-883
33. Scott G.M., Weinberg A., Rawlinson W.D., and Chou S. Multidrug resistance conferred by novel DNA polymerase mutations in human cytomegalovirus isolates. Antimicrob Agents Chemother 51 (2007) 89-94
34. Ciesla S.L., Trahan J., Wan W.B., Beadle J.R., Aldern K.A., Painter G.R., and Hostetler K.Y. Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney. Antiviral Res 59 (2003) 163-171
35. Quenelle D.C., Collins D.J., Pettway L.R., Hartline C.B., Beadle J.R., Wan W.B., Hostetler K.Y., and Kern E.R. Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on replication of murine cytomegalovirus (MCMV) or human cytomegalovirus (HCMV) in animal models. Antiviral Res 79 (2008) 133-135
36. Kern E.R., Collins D.J., Wan W.B., Beadle J.R., Hostetler K.Y., and Quenelle D.C. Oral treatment of murine cytomegalovirus infections with ether lipid esters of cidofovir. Antimicrob Agents Chemother 48 (2004) 3516-3522
37. Adjuik M., Babiker A., Garner P., Olliaro P., Taylor W., and White N. Artesunate combinations for treatment of malaria: meta-analysis. Lancet 363 (2004) 9-17
38. Efferth T., Marschall M., Wang X., Huong S.M., Hauber I., Olbrich A., Kronschnabl M., Stamminger T., and Huang E.S. Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses. J Mol Med 80 (2002) 233-242
39. Kaptein S.J., Efferth T., Leis M., Rechter S., Auerochs S., Kalmer M., Bruggeman C.A., Vink C., Stamminger T., and Marschall M. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res 69 (2006) 60-69
40. Shapira M.Y., Resnick I.B., Chou S., Neumann A.U., Lurain N.S., Stamminger T., Caplan O., Saleh N., Efferth T., Marschall M., and Wolf D.G. Artesunate as a potent antiviral agent in a patient with late drug-resistant cytomegalovirus infection after hematopoietic stem cell transplantation. Clin Infect Dis 46 (2008) 1455-1457. First case report on successful artesunate treatment of a patient with resistant HCMV after stem cell transplantation.
41. Buerger I., Reefschlaeger J., Bender W., Eckenberg P., Popp A., Weber O., Graeper S., Klenk H.D., Ruebsamen-Waigmann H., and Hallenberger S. A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA maturation via the UL89 and UL56 gene products. J Virol 75 (2001) 9077-9086
42. Weber O., Bender W., Eckenberg P., Goldmann S., Haerter M., Hallenberger S., Henninger K., Reefschlager J., Trappe J., Witt-Laido A., and Ruebsamen-Waigmann H. Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo. Antiviral Res 49 (2001) 179-189
43. Reefschlaeger J., Bender W., Hallenberger S., Weber O., Eckenberg P., Goldmann S., Haerter M., Buerger I., Trappe J., Herrington J.A., et al. Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action. J Antimicrob Chemother 48 (2001) 757-767
44. Underwood M.R., Harvey R.J., Stanat S.C., Hemphill M.L., Miller T., Drach J.C., Townsend L.B., and Biron K.K. Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product. J Virol 72 (1998) 717-725
45. Krosky P.M., Underwood M.R., Turk S.R., Feng K.W., Jain R.K., Ptak R.G., Westerman A.C., Biron K.K., Townsend L.B., and Drach J.C. Resistance of human cytomegalovirus to benzimidazole ribonucleosides maps to two open reading frames: UL89 and UL56. J Virol 72 (1998) 4721-4728
46. Chulay J., Biron K., Wang L., Underwood M., Chamberlain S., Frick L., Good S., Davis M., Harvey R., Townsend L., et al. Development of novel benzimidazole riboside compounds for treatment of cytomegalovirus disease. Adv Exp Med Biol 458 (1999) 129-134
47. Williams S.L., Hartline C.B., Kushner N.L., Harden E.A., Bidanset D.J., Drach J.C., Townsend L.B., Underwood M.R., Biron K.K., and Kern E.R. In vitro activities of benzimidazole d- and l-ribonucleosides against herpesviruses. Antimicrob Agents Chemother 47 (2003) 2186-2192
48. Underwood M.R., Ferris R.G., Selleseth D.W., Davis M.G., Drach J.C., Townsend L.B., Biron K.K., and Boyd F.L. Mechanism of action of the ribopyranoside benzimidazole GW275175X against human cytomegalovirus. Antimicrob Agents Chemother 48 (2004) 1647-1651
49. Biron K.K., Harvey R.J., Chamberlain S.C., Good S.S., Smith III A.A., Davis M.G., Talarico C.L., Miller W.H., Ferris R., Dornsife R.E., et al. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole l-riboside with a unique mode of action. Antimicrob Agents Chemother 46 (2002) 2365-2372
50. Wolf D.G., Courcelle C.T., Prichard M.N., and Mocarski E.S. Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc Natl Acad Sci U S A 98 (2001) 1895-1900
51. Krosky P.M., Baek M.C., and Coen D.M. The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J Virol 77 (2003) 905-914
52. Lalezari J.P., Aberg J.A., Wang L.H., Wire M.B., Miner R., Snowden W., Talarico C.L., Shaw S., Jacobson M.A., and Drew W.L. Phase I dose escalation trial evaluating the pharmacokinetics, anti-human cytomegalovirus (HCMV) activity, and safety of 1263W94 in human immunodeficiency virus-infected men with asymptomatic HCMV shedding. Antimicrob Agents Chemother 46 (2002) 2969-2976
53. Winston D.J., Young J.A., Pullarkat V., Papanicolaou G.A., Vij R., Vance E., Alangaden G.J., Chemaly R.F., Petersen F., Chao N., et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. Blood 111 (2008) 5403-5410. First analysis on Phase II data of a novel anti-HCMV compound.