In vitro drug combination studies of letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV Replication

Antimicrobial Agents and Chemotherapy

Volumn 59, Issue 6, 2015, Pages 3140-3148

  Wildum, Steffen ^a,b   Zimmermann, Holger ^a   Lischka, Peter ^a  

^a AiCuris GmbH   (Germany)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; ATAZANAVIR; CIDOFOVIR; DARUNAVIR; EFAVIRENZ; ELVITEGRAVIR; EMTRICITABINE; ETRAVIRINE; FOSCARNET; GANCICLOVIR; LETERMOVIR; LOPINAVIR; NEVIRAPINE; RALTEGRAVIR; RILPIVIRINE; RITONAVIR; TENOFOVIR; ACETIC ACID DERIVATIVE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIVIRUS AGENT; DRUG COMBINATION; QUINAZOLINE DERIVATIVE;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG ANTAGONISM; DRUG APPROVAL; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG INHIBITION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; HUMAN CYTOMEGALOVIRUS; HUMAN IMMUNODEFICIENCY VIRUS; IN VITRO STUDY; PRIORITY JOURNAL; VIRUS REPLICATION; ANTIVIRAL RESISTANCE; CELL LINE; CYTOMEGALOVIRUS; DRUG COMBINATION; DRUG EFFECTS;

ACETATES; ANTI-HIV AGENTS; ANTIVIRAL AGENTS; CELL LINE; CYTOMEGALOVIRUS; DRUG COMBINATIONS; DRUG RESISTANCE, VIRAL; HUMANS; QUINAZOLINES; VIRUS REPLICATION;

EID: 84929648692     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00114-15     Document Type: Article

References (46)

1. Sampathkumar P, Paya C. 2007. Pathogenesis in transplant recipients. In Emery VC (ed), Human cytomegalovirus. International Medical Press, London, United Kingdom.
2. Steininger C, Puchhammer-Stockl E, Popow-Kraupp T. 2006. Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART). J Clin Virol 37:1-9. http://dx.doi.org/10.1016/j.jcv.2006.03.005.
3. Kotton CN. 2013. CMV: prevention, diagnosis and therapy. Am J Transplant 13(Suppl 3):S24-S40. http://dx.doi.org/10.1111/ajt.12006.
4. Ljungman P, Hakki M, Boeckh M. 2011. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am 25:151-169. http://dx.doi.org/10.1016/j.hoc.2010.11.011.
5. Beam E, Razonable RR. 2012. Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment. Curr Infect Dis Rep 14:633-641. http://dx.doi.org/10.1007/s11908-012-0292-2.
6. Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L, Humar A. 2013. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 96:333-360. http://dx.doi.org/10.1097/TP.0b013e31829df29d.
7. Pertel P, Hirschtick R, Phair J, Chmiel J, Poggensee L, Murphy R. 1992. Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus. J Acquir Immune Defic Syndr 5:1069-1074.
8. Gallant JE, Moore RD, Richman DD, Keruly J, Chaisson RE. 1992. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group. J Infect Dis 166:1223-1227.
9. Kedhar SR, Jabs DA. 2007. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Herpes 14:66-71.
10. Losina E, Schackman BR, Sadownik SN, Gebo KA, Walensky RP, Chiosi JJ, Weinstein MC, Hicks PL, Aaronson WH, Moore RD, Paltiel AD, Freedberg KA. 2009. Racial and sex disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis 49:1570-1578. http://dx.doi.org/10.1086/644772.
11. Appay V, Fastenackels S, Katlama C, Ait-Mohand H, Schneider L, Guihot A, Keller M, Grubeck-Loebenstein B, Simon A, Lambotte O, Hunt PW, Deeks SG, Costagliola D, Autran B, Sauce D. 2011. Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients. AIDS 25:1813-1822. http://dx.doi.org/10.1097/QAD.0b013e32834640e6.
12. Hunt PW, Martin JN, Sinclair E, Epling L, Teague J, Jacobson MA, Tracy RP, Corey L, Deeks SG. 2011. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis 203:1474-1483. http://dx.doi.org/10.1093/infdis/jir060.
13. Biron KK. 2006. Antiviral drugs for cytomegalovirus diseases. Antiviral Res 71:154-163. http://dx.doi.org/10.1016/j.antiviral.2006.05.002.
14. Lischka P, Zimmermann H. 2008. Antiviral strategies to combat cytomegalovirus infections in transplant recipients. Curr Opin Pharmacol 8:541-548. http://dx.doi.org/10.1016/j.coph.2008.07.002.
15. Harter G, Michel D. 2012. Antiviral treatment of cytomegalovirus infection: an update. Expert Opin Pharmacother 13:623-627. http://dx.doi.org/10.1517/14656566.2012.658775.
16. Lurain NS, Chou S. 2010. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23:689-712. http://dx.doi.org/10.1128/CMR.00009-10.
17. Le Page AK, Jager MM, Iwasenko JM, Scott GM, Alain S, Rawlinson WD. 2013. Clinical aspects of cytomegalovirus antiviral resistance in solid organ transplant recipients. Clin Infect Dis 56:1018-1029. http://dx.doi.org/10.1093/cid/cis1035.
18. Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-Schaeff H, Zimmermann H. 2010. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 54:1290-1297. http://dx.doi.org/10.1128/AAC.01596-09.
19. Stoelben S, Arns W, Renders L, Hummel J, Muhlfeld A, Stangl M, Fischereder M, Gwinner W, Suwelack B, Witzke O, Durr M, Beelen DW, Michel D, Lischka P, Zimmermann H, Rubsamen-Schaeff H, Budde K. 2014. Preemptive treatment of cytomegalovirus infection in kidney transplant recipients with letermovir: results of a phase 2a study. Transpl Int 27:77-86. http://dx.doi.org/10.1111/tri.12225.
20. Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, Kolling K, Stobernack HP, Lischka P, Zimmermann H, Rubsamen-Schaeff H, Champlin RE, Ehninger G. 2014. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med 370:1781-1789. http://dx.doi.org/10.1056/NEJMoa1309533.
21. Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 2011. The novel anticytomegalovirus compound AIC246 (letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol 85:10884-10893. http://dx.doi.org/10.1128/JVI.05265-11.
22. Marschall M, Stamminger T, Urban A, Wildum S, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 2012. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother 56:1135-1137. http://dx.doi.org/10.1128/AAC.05908-11.
23. Kaul DR, Stoelben S, Cober E, Ojo T, Sandusky E, Lischka P, Zimmermann H, Rubsamen-Schaeff H. 2011. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant 11:1079-1084. http://dx.doi.org/10.1111/j.1600-6143.2011.03530.x.
24. Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 2014. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother 58:610-613. http://dx.doi.org/10.1128/AAC.01794-13.
25. Reddy SM, Winston DJ, Territo MC, Schiller GJ. 2010. CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency. Bone Marrow Transplant 45:979-984. http://dx.doi.org/10.1038/bmt.2010.35.
26. Maschke M, Kastrup O, Diener HC. 2002. CNS manifestations of cytomegalovirus infections: diagnosis and treatment. CNS Drugs 16:303-315. http://dx.doi.org/10.2165/00023210-200216050-00003.
27. Griffiths P. 2004. Cytomegalovirus infection of the central nervous system. Herpes 11(Suppl 2):95A-104A.
28. Wildum S, Paulsen D, Thede K, Ruebsamen-Schaeff H, Zimmermann H. 2013. In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother 57:5320-5329. http://dx.doi.org/10.1128/AAC.01377-13.
29. Borst EM, Wagner K, Binz A, Sodeik B, Messerle M. 2008. The essential human cytomegalovirus gene UL52 is required for cleavage-packaging of the viral genome. J Virol 82:2065-2078. http://dx.doi.org/10.1128/JVI.01967-07.
30. Borst EM, Messerle M. 2005. Analysis of human cytomegalovirus oriLyt sequence requirements in the context of the viral genome. J Virol 79:3615-3626. http://dx.doi.org/10.1128/JVI.79.6.3615-3626.2005.
31. Andreoni M, Faircloth M, Vugler L, Britt WJ. 1989. A rapid microneutralization assay for the measurement of neutralizing antibody reactive with human cytomegalovirus. J Virol Methods 23:157-167. http://dx.doi.org/10.1016/0166-0934(89)90129-8.
32. Lorz K, Hofmann H, Berndt A, Tavalai N, Mueller R, Schlotzer-Schrehardt U, Stamminger T. 2006. Deletion of open reading frame UL26 from the human cytomegalovirus genome results in reduced viral growth, which involves impaired stability of viral particles. J Virol 80:5423-5434. http://dx.doi.org/10.1128/JVI.02585-05.
33. Prichard MN, Shipman C, Jr. 1990. A three-dimensional model to analyze drug-drug interactions. Antiviral Res 14:181-205. http://dx.doi.org/10.1016/0166-3542(90)90001-N.
34. Chou TC, Talalay P. 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27-55. http://dx.doi.org/10.1016/0065-2571(84)90007-4.
35. Lai MT, Munshi V, Touch S, Tynebor RM, Tucker TJ, McKenna PM, Williams TM, Distefano DJ, Hazuda DJ, Miller MD. 2009. Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother 53:2424-2431. http://dx.doi.org/10.1128/AAC.01559-08.
36. Chou TC. 2006. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58:621-681. http://dx.doi.org/10.1124/pr.58.3.10.
37. Azijn H, Tirry I, Vingerhoets J, de Bethune MP, Kraus G, Boven K, Jochmans D, Van CE, Picchio G, Rimsky LT. 2010. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother 54:718-727. http://dx.doi.org/10.1128/AAC.00986-09.
38. Greco WR, Bravo G, Parsons JC. 1995. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev 47:331-385.
39. Bassit L, Grier J, Bennett M, Schinazi RF. 2008. Combinations of 2′-C-methylcytidine analogues with interferon-alpha2b and triple combination with ribavirin in the hepatitis C virus replicon system. Antivir Chem Chemother 19:25-31. http://dx.doi.org/10.1177/095632020801900104.
40. Food and Drug Administration Center for Drug Evaluation and Research. 2006. Guidance for industry: antiviral product development - conducting and submitting virology studies to the agency. FDA, Washington, DC.
41. Volberding PA, Deeks SG. 2010. Antiretroviral therapy and management of HIV infection. Lancet 376:49-62. http://dx.doi.org/10.1016/S0140-6736(10)60676-9.
42. Ilyas JA, Vierling JM. 2014. An overview of emerging therapies for the treatment of chronic hepatitis C. Med Clin North Am 98:17-38. http://dx.doi.org/10.1016/j.mcna.2013.10.011.
43. Butler NJ, Thorne JE. 2012. Current status of HIV infection and ocular disease. Curr Opin Ophthalmol 23:517-522. http://dx.doi.org/10.1097/ICU.0b013e328358ba85.
44. Griffiths PD, Emery VC. 2014. Taming the transplantation troll by targeting terminase. N Engl J Med 370:1844-1846. http://dx.doi.org/10.1056/NEJMe1401567.
45. Delaney WE, Yang H, Miller MD, Gibbs CS, Xiong S. 2004. Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. Antimicrob Agents Chemother 48:3702-3710. http://dx.doi.org/10.1128/AAC.48.10.3702-3710.2004.
46. Evers DL, Komazin G, Shin D, Hwang DD, Townsend LB, Drach JC. 2002. Interactions among antiviral drugs acting late in the replication cycle of human cytomegalovirus. Antiviral Res 56:61-72. http://dx.doi.org/10.1016/S0166-3542(02)00094-3.