Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-f554764f5-wjqwx Total loading time: 0 Render date: 2025-04-22T16:18:47.463Z Has data issue: false hasContentIssue false

66 - Antiviral therapy for human cytomegalovirus

from Part VI - Antiviral therapy

Published online by Cambridge University Press:  24 December 2009

By
Paul D. Griffiths  and
Michael Boeckh
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Paul D. Griffiths
Affiliation:
Royal Free and University College Medical School, London, UK
Michael Boeckh
Affiliation:
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
Get access

Summary

Introduction

The remit of this chapter is to summarize what is known about licensed antiviral drugs for CMV. In summary, we do not possess a single anti-CMV drug, which is potent and safe enough to be given to all individuals infected with this virus. What follows therefore, is the evidence-base for prescribing the existing compounds with the objective of maximizing therapeutic efficacy and cost-effectiveness while minimizing toxicity.

Licensed drugs and mechanism of action

Nucleosides

Ganciclovir (GCV) and acyclovir (ACV) are related nucleosides (see Fig. 66.1) which are anabolized by a common cellular pathway. After activation, they are competitive inhibitors of CMV encoded DNA polymerase. In cells infected with CMV, the first stage of phosphorylation is achieved by the UL97 protein kinase. Once GCV is mono-phosphorylated within the virus-infected cell, it is charged and so unable to diffuse out of the cell. A concentration gradient is thereby formed across the plasma membrane, aiding diffusion of more GCV into the infected cell. Cellular enzymes convert GCV monophosphate to the triphosphate. GCV triphosphate is a potent inhibitor of CMV DNA polymerase and has a long intracellular half-life. Selectivity for virus-infected cells is achieved both by UL97 activation and because GCV triphosphate is a better inhibitor of CMV-encoded DNA polymerase than cellular DNA polymerase.

Ganciclovir possesses a free hydroxyl at a position equivalent to the 3' of the open sugar ring and so can allow DNA elongation.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 1192 - 1210
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Adler, H., Messerle, M., and Koszinowski, U. H. (2003). Cloning of herpesviral genomes as bacterial artificial chromosomes. Rev. Med. Virol., 13(2), 111–121.CrossRefGoogle ScholarPubMed
Balfour, H. H. Jr., Chace, B. A., Stapleton, J. T., Simmons, R. L., and Fryd, D. S. (1989). A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. N. Engl. J. Med., 320(21), 1381–1387.CrossRefGoogle ScholarPubMed
Betts, R. F., Freeman, R. B., Douglas, R. G. Jr., and Talley, T. E. (1977). Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Am. J. Dis. Child., 131(7), 759–763.Google ScholarPubMed
Boeckh, M. and Nichols, W. G. (2003). Immunosuppressive effects of beta-herpesviruses. Herpes, 10(1), 12–16.Google ScholarPubMed
Boeckh, M. and Nichols, W. G. (2004). The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood, 103(6), 2003–2008.CrossRefGoogle ScholarPubMed
Boeckh, M., Gooley, T. A., Myerson, D., Cunningham, T., Schoch, G., and Bowden, R. A. (1996). Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood, 88(10), 4063–4071.Google ScholarPubMed
Boeckh, M., Bowden, R. A., Storer, B.et al. (2001). Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transpl., 7(6), 343–351.CrossRefGoogle ScholarPubMed
Boivin, G., Gilbert, C., Gaudreau, A., Greenfield, I., Sudlow, R., and Roberts, N. A. (2001). Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis. J. Infect. Dis., 184(12), 1598–1602.CrossRefGoogle ScholarPubMed
Bowden, R. A., Fisher, L. D., Rogers, K., Cays, M., and Meyers, J. D. (1991). Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV infection and disease after marrow transplant. J. Infect. Dis., 164(3), 483–487.CrossRefGoogle ScholarPubMed
Bowen, E. F., Wilson, P., Cope, A.et al. (1996). Cytomegalovirus retinitis in AIDS patients: influence of cytomegaloviral load on response to ganciclovir, time to recurrence and survival. AIDS, 10(13), 1515–1520.CrossRefGoogle ScholarPubMed
Bowen, E. F., Emery, V. C., Wilson, P.et al. (1998). Cytomegalovirus polymerase chain reaction viraemia in patients receiving ganciclovir maintenance therapy for retinitis. AIDS, 12(6), 605–611.CrossRefGoogle ScholarPubMed
Cheeseman, S. H., Rubin, R. H., Stewart, J. A.et al. (1979). Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections. N. Engl. J. Med., 300(24), 1345–1349.CrossRefGoogle ScholarPubMed
Chou, S., Miner, R. C., and Drew, W. L. (2000). A deletion mutation in region V of the cytomegalovirus DNA polymerase sequence confers multidrug resistance. J. Infect. Dis., 182(6), 1765–1768.CrossRefGoogle ScholarPubMed
Chou, S., Waldemer, R. H., Senters, A. E.et al. (2002). Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J. Infect. Dis., 185(2), 162–169.CrossRefGoogle ScholarPubMed
Chou, S., Lurain, N. S., Thompson, K. D., Miner, R. C., and Drew, W. L. (2003). Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J. Infect. Dis., 188(1), 32–39.CrossRefGoogle ScholarPubMed
Cope, A. V., Sabin, C., Burroughs, A., Rolles, K., Griffiths, P. D., and Emery, V. C. (1997a). Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J. Infect. Dis., 176(6), 1484–1490.CrossRefGoogle Scholar
Cope, A. V., Sweny, P., Sabin, C., Rees, L., Griffiths, P. D., and Emery, V. C. (1997b). Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus disease after renal transplantation. J. Med. Virol., 52(2), 200–205.3.0.CO;2-O>CrossRefGoogle Scholar
Crippa, F., Corey, L., Chuang, E. L., Sale, G., and Boeckh, M. (2001). Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. Clin. Infect. Dis., 32(2), 214–219.CrossRefGoogle ScholarPubMed
Deayton, J., Mocroft, A., Wilson, P., Emery, V. C., Johnson, M. A., and Griffiths, P. D. (1999). Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy. AIDS, 13(10), 1203–1206.CrossRefGoogle ScholarPubMed
Deayton, J. R., Sabin, C., Johnson, M. A., Emery, V. C., Wilson, P., and Griffiths, P. D. (2004). Cytomegalovirus viraemia remains an important risk factor for disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy. Lancet, 363(9427), 2116–2121.CrossRefGoogle Scholar
De Clercq, E., Naesens, L., De Bolle, L., Schols, D., Zhang, Y., and Neyts, J. (2001). Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8. Rev. Med. Virol., 11(6), 381–395.CrossRefGoogle ScholarPubMed
Drew, W. L., Miner, R. C., Busch, D. F.et al. (1991). Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection. J. Infect. Dis., 163(4), 716–719.CrossRefGoogle ScholarPubMed
Einsele, H., Ehninger, G., Hebart, H.et al. (1995). Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood, 86(7), 2815–2820.Google ScholarPubMed
Emery, V. C. and Griffiths, P. D. (2000). Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy. Proc. Natl Acad. Sci. USA, 97(14), 8039–8044.CrossRefGoogle ScholarPubMed
Emery, V. C., Cope, A. V., Bowen, E. F., Gor, D., and Griffiths, P. D. (1999). The dynamics of human cytomegalovirus replication in vivo. J. Exp. Med., 190(2), 177–182.CrossRefGoogle ScholarPubMed
Emery, V. C., Sabin, C. A., Cope, A. V., Gor, D., Hassan-Walker, A. F., and Griffiths, P. D. (2000). Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet, 355(9220), 2032–2036.CrossRefGoogle ScholarPubMed
Emery, V. C., Hassan-Walker, A. F., Burroughs, A. K., and Griffiths, P. D. (2002). Human cytomegalovirus (HCMV) replication dynamics in HCMV-naive and -experienced immunocompromised hosts. J. Infect. Dis., 185(12), 1723–1728.CrossRefGoogle ScholarPubMed
Erice, A., Chou, S., Biron, K. K., Stanat, S. C., Balfour, H. H. Jr., and Jordan, M. C. (1989). Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N. Engl. J. Med., 320(5), 289–293.CrossRefGoogle ScholarPubMed
Falagas, M. E., Snydman, D. R., Griffith, J., and Werner, B. G. (1996). Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group. Clin. Infect. Dis., 23(3), 468–474.CrossRefGoogle ScholarPubMed
Feinberg, J. E., Hurwitz, S., Cooper, D.et al. (1998). A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. J. Infect. Dis., 177(1), 48–56.CrossRefGoogle Scholar
Fletcher, C. V., Englund, J. A., Edelman, C. K., Gross, C. R., Dunn, D. L., and Balfour, H. H. (1991). Jr. Pharmacologic basis for high-dose oral acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients. Antimicrob. Agents Chemother., 35(5), 938–943.CrossRefGoogle Scholar
Furman, P. A., St. Clair, M. H., and Spector, T. (1984). Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase. J. Biol. Chem., 259(15), 9575–9579.Google ScholarPubMed
Gane, E., Saliba, F., Valdecasas, G. J.et al. (1997). Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected]. Lancet, 350(9093), 1729–1733.CrossRefGoogle Scholar
Gerna, G., Baldanti, F., Lilleri, D.et al. (2003a). Human cytomegalovirus pp67 mRNAemia versus pp65 antigenemia for guiding preemptive therapy in heart and lung transplant recipients: a prospective, randomized, controlled, open-label trial. Transplantation, 75(7), 1012–1019.CrossRefGoogle Scholar
Gerna, G., Lilleri, D., Baldanti, F.et al. (2003b). Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial. Blood, 101(12), 5053–5060.CrossRefGoogle Scholar
Gilbert, C. and Boivin, G. (2003). Discordant phenotypes and genotypes of cytomegalovirus (CMV) in patients with AIDS and relapsing CMV retinitis. AIDS, 17(3), 337–341.CrossRefGoogle ScholarPubMed
Gleaves, C. A., Smith, T. F., Shuster, E. A., and Pearson, G. R. (1984). Rapid detection of cytomegalovirus in MRC-5 cells inoculated with urine specimens by using low-speed centrifugation and monoclonal antibody to an early antigen. J. Clin. Microbiol., 19(6), 917–919.Google Scholar
Goodrich, J. M., Mori, M., Gleaves, C. A.et al. (1991). Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N. Engl. J. Med., 325(23), 1601–1607.CrossRefGoogle ScholarPubMed
Goodrich, J. M., Bowden, R. A., Fisher, L., Keller, C., Schoch, G., and Meyers, J. D. (1993). Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann. Intern. Med., 118(3), 173–178.CrossRefGoogle ScholarPubMed
Gor, D., Sabin, C., Prentice, H. G.et al. (1998). Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease. Bone Marrow Transpl., 21(6), 597–605.CrossRefGoogle ScholarPubMed
Grattan, M. T., Moreno-Cabral, C. E., Starnes, V. A., Oyer, P. E., Stinson, E. B., and Shumway, N. E. (1989). Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. J. Am. Med. Assoc., 261(24), 3561–3566.CrossRefGoogle ScholarPubMed
Griffiths, P. D. (2002). The 2001 Garrod lecture. The treatment of cytomegalovirus infection. J. Antimicrob. Chemother., 49(2), 243–253.CrossRefGoogle ScholarPubMed
Griffiths, P. D. and McLaughlin, J. E. (1997). Cytomegalovirus. Infect. Centr. Nerv. Syst., 107–115.Google Scholar
Griffiths, P. D., Panjwani, D. D., Stirk, P. R.et al. (1984). Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by detection of early antigen fluorescent foci. Lancet, 2(8414), 1242–1245.CrossRefGoogle ScholarPubMed
Griffiths, P. D., Feinberg, J. E., Fry, J.et al. (1998). The effect of valaciclovir on cytomegalovirus viremia and viruria detected by polymerase chain reaction in patients with advanced human immunodeficiency virus disease. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. J. Infect. Dis., 177(1), 57–64.CrossRefGoogle Scholar
Grundy, J. E., Shanley, J. D., and Griffiths, P. D. (1987). Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition?Lancet, 2(8566), 996–999.CrossRefGoogle ScholarPubMed
Grundy, J. E., Lui, S. F., Super, M.et al. (1988). Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet, 2(8603), 132–135.CrossRefGoogle ScholarPubMed
Guetta, E., Guetta, V., Shibutani, T., and Epstein, S. E. (1997). Monocytes harboring cytomegalovirus: interactions with endothelial cells, smooth muscle cells, and oxidized low-density lipoprotein. Possible mechanisms for activating virus delivered by monocytes to sites of vascular injury. Circ. Res., 81(1), 8–16.CrossRefGoogle ScholarPubMed
Hassan-Walker, A. F., Kidd, I. M., Sabin, C., Sweny, P., Griffiths, P. D., and Emery, V. C. (1999). Quantity of human cytomegalovirus (CMV) DNAemia as a risk factor for CMV disease in renal allograft recipients: relationship with donor/recipient CMV serostatus, receipt of augmented methylprednisolone and antithymocyte globulin (ATG). J. Med. Virol., 58(2), 182–187.3.0.CO;2-Q>CrossRefGoogle Scholar
Hibberd, P. L., Tolkoff-Rubin, N. E., Conti, D.et al. (1995). Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. A randomized controlled trial. Ann. Intern. Med., 123(1), 18–26.CrossRefGoogle ScholarPubMed
Hirsch, M. S., Schooley, R. T., Cosimi, A. B., et al. (1983). Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients. N. Engl. J. Med., 308(25), 1489–1493.CrossRefGoogle ScholarPubMed
Hu, H., Jabs, D. A., Forman, M. S.et al. (2002). Comparison of cytomegalovirus (CMV) UL97 gene sequences in the blood and vitreous of patients with acquired immunodeficiency syndrome and CMV retinitis. J. Infect. Dis., 185(7), 861–867.CrossRefGoogle ScholarPubMed
Humar, A., Lipton, J., Welsh, S., Moussa, G., Messner, H., and Mazzulli, T. (2001). A randomised trial comparing cytomegalovirus antigenemia assay vs screening bronchoscopy for the early detection and prevention of disease in allogeneic bone marrow and peripheral blood stem cell transplant recipients. Bone Marrow Transpl., 28(5), 485–490.CrossRefGoogle ScholarPubMed
Jacobson, M. A. (1997). Treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med., 337(2), 105–114.CrossRefGoogle ScholarPubMed
Jacobson, M. A., Zegans, M., Pavan, P. R.et al. (1997). Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy. Lancet, 349(9063), 1443–1445.CrossRefGoogle ScholarPubMed
Karavellas, M. P., Plummer, D. J., Macdonald, J. C.et al. (1999). Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J. Infect. Dis., 179(3), 697–700.CrossRefGoogle ScholarPubMed
Kawaguchi, Y. and Kato, K. (2003). Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. Rev. Med. Virol., 13(5), 331–340.CrossRefGoogle Scholar
Kidd, I. M., Fox, J. C., Pillay, D., Charman, H., Griffiths, P. D., and Emery, V. C. (1993). Provision of prognostic information in immunocompromised patients by routine application of the polymerase chain reaction for cytomegalovirus. Transplantation, 56(4), 867–871.CrossRefGoogle ScholarPubMed
Kimberlin, D. W., Lin, C. Y., Sanchez, P. J.et al. (2003). Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J. Pediatr., 143(1), 16–25.CrossRefGoogle ScholarPubMed
Krosky, P. M., Baek, M. C., and Coen, D. M. (2003). The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J. Virol., 77(2), 905–914.CrossRefGoogle ScholarPubMed
Lemstrom, K., Sihvola, R., Bruggeman, C., Hayry, P., and Koskinen, P. (1997). Cytomegalovirus infection-enhanced cardiac allograft vasculopathy is abolished by DHPG prophylaxis in the rat. Circulation, 95(12), 2614–2616.CrossRefGoogle ScholarPubMed
Limaye, A. P., Corey, L., Koelle, D. M., Davis, C. L., and Boeckh, M. (2000). Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet, 356(9230), 645–649.CrossRefGoogle ScholarPubMed
Lin, D. Y., Warren, J. F., Lazzeroni, L. C., Wolitz, R. A., and Mansour, S. E. (2002). Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy in HIV infected patients: natural history and clinical predictors. Retina, 22(3), 268–277.CrossRefGoogle ScholarPubMed
Liu, W., Shum, C., Martin, D. F., Kuppermann, B. D., Hall, A. J., and Margolis, T. P. (2000). Prevalence of antiviral drug resistance in untreated patients with cytomegalovirus retinitis. J. Infect. Dis., 182(4), 1234–1238.CrossRefGoogle ScholarPubMed
Ljungman, P., Engelhard, D., Link, H.et al. (1992). Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group. Clin. Infect. Dis., 14(4), 831–835.CrossRefGoogle ScholarPubMed
Ljungman, P., Griffiths, P., and Paya, C. (2002). Definitions of cytomegalovirus infection and disease in transplant recipients. Clin. Infect. Dis., 34(8), 1094–1097.CrossRefGoogle ScholarPubMed
Lowance, D., Neumayer, H. H., Legendre, C. M.et al. (1999). Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N. Engl. J. Med., 340(19), 1462–1470.CrossRefGoogle ScholarPubMed
Lui, S. F., Ali, A. A., Grundy, J. E., Fernando, O. N., Griffiths, P. D., and Sweny, P. (1992). Double-blind, placebo-controlled trial of human lymphoblastoid interferon prophylaxis of cytomegalovirus infection in renal transplant recipients. Nephrol. Dial. Transpl., 7(12), 1230–1237.CrossRefGoogle ScholarPubMed
Macdonald, P. S., Keogh, A. M., Marshman, D.et al. (1995). A double-blind placebo-controlled trial of low-dose ganciclovir to prevent cytomegalovirus disease after heart transplantation. J. Heart Lung Transpl., 14(1 Pt 1), 32–38.Google ScholarPubMed
Mar, E. C., Huang, E. S., Cheng, Y. C., and Chiou, J. F. (1985). Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphates of 9-(2-hydroxyethoxymethyl)guanine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine. J. Virol., 53(3), 776–780.Google ScholarPubMed
Martin, D. F., Sierra-Madero, J., Walmsley, S.et al. (2002). A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N. Engl. J. Med., 346(15), 1119–1126.CrossRefGoogle ScholarPubMed
Mattes, F. M., McLaughlin, J. E., Emery, V. C., Clark, D. A., and Griffiths, P. D. (2000). Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7. J. Clin. Pathol., 53(8), 612–614.CrossRefGoogle ScholarPubMed
Mattes, F. M., Hainsworth, E. G., Geretti, A. M., et al. (2004). A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients. J. Infect. Dis., 189(8), 1355–1361.CrossRefGoogle ScholarPubMed
Merigan, T. C., Renlund, D. G., Keay, S.et al. (1992). A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation. N. Engl. J. Med., 326(18), 1182–1186.CrossRefGoogle ScholarPubMed
Metselaar, H. J., Rothbarth, P. H., Brouwer, R. M., Wenting, G. J., Jeekel, J., and Weimar, W. (1989). Prevention of cytomegalovirus-related death by passive immunization. A double-blind placebo-controlled study in kidney transplant recipients treated for rejection. Transplantation, 48(2), 264–266.CrossRefGoogle ScholarPubMed
Meyers, J. D., Ljungman, P., and Fisher, L. D. (1990). Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia. J. Infect. Dis., 162(2), 373–380.CrossRefGoogle ScholarPubMed
Nichols, W. G., Corey, L., Gooley, T., Davis, C., and Boeckh, M. (2002). High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J. Infect. Dis., 185(3), 273–282.CrossRefGoogle ScholarPubMed
Paya, C., Humar, A., Dominguez, E.et al. (2004). Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am. J. Transpl., 4(4), 611–620.CrossRefGoogle ScholarPubMed
Paya, C. V., Wilson, J. A., Espy, M. J., et al. (2002). Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J. Infect. Dis., 185(7), 854–860.CrossRefGoogle ScholarPubMed
Prentice, H. G., Gluckman, E., Powles, R. L.et al. (1994). Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet, 343(8900), 749–753.CrossRefGoogle ScholarPubMed
Razonable, R. R., Brown, R. A., Wilson, J.et al. (2002). The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation, 73(6), 968–973.CrossRefGoogle ScholarPubMed
Reed, E. C., Wolford, J. L., Kopecky, K. J.et al. (1990). Ganciclovir for the treatment of cytomegalovirus gastroenteritis in bone marrow transplant patients. A randomized, placebo-controlled trial. Ann. Intern. Med., 112(7), 505–510.CrossRefGoogle ScholarPubMed
Reinke, P., Fietze, E., Ode-Hakim, S.et al. (1994). Late-acute renal allograft rejection and symptomless cytomegalovirus infection. Lancet, 344(8939–8940), 1737–1738.CrossRefGoogle ScholarPubMed
Reusser, P., Einsele, H., Lee, J.et al. (2002). Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood, 99(4), 1159–1164.CrossRefGoogle ScholarPubMed
Rubin, R. H. (1991). Preemptive therapy in immunocompromised hosts. N. Engl. J. Med., 324(15), 1057–1059.CrossRefGoogle ScholarPubMed
Safrin, S., Cherrington, J., and Jaffe, H. S. (1997). Clinical uses of cidofovir. Rev. Med. Virol., 7(3), 145–156.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Schmidt, G. M., Horak, D. A., Niland, J. C., Duncan, S. R., Forman, S. J., and Zaia, J. A. (1991). A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N. Engl. J. Med., 324(15), 1005–1011.CrossRefGoogle ScholarPubMed
Shinkai, M. and Spector, S. A. (1995). Quantitation of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid by competitive PCR in AIDS patients with different HCMV central nervous system diseases. Scand. J. Infect. Dis., 27(6), 559–561.CrossRefGoogle ScholarPubMed
Singh, N. (2006). Antiviral drugs for cytomegalovirus in transplant recipients: advantages of preemptive therapy. Rev. Med. Virol., 16(5), 281–287.CrossRefGoogle ScholarPubMed
Snydman, D. R., Werner, B. G., Dougherty, N. N.et al. (1993). Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial. The Boston Center for Liver Transplantation CMVIG Study Group. Ann. Intern. Med., 119(10), 984–991.CrossRefGoogle Scholar
Snydman, D. R. (2006). The case for cytomegalovirus prophylaxis in solid organ transplantation. Rev. Med. Virol. 16(5), 289–295.CrossRefGoogle ScholarPubMed
Spector, S. A., Merrill, R., Wolf, D., and Dankner, W. M. (1992). Detection of human cytomegalovirus in plasma of AIDS patients during acute visceral disease by DNA amplification. J. Clin. Microbiol., 30(9), 2359–2365.Google ScholarPubMed
Spector, S. A., McKinley, G. F., Lalezari, J. P.et al. (1996). Oral ganciclovir for the prevention of cytomegalovirus disease in persons with AIDS. Roche Cooperative Oral Ganciclovir Study Group. N. Engl. J. Med., 334(23), 1491–1497.CrossRefGoogle ScholarPubMed
Spector, S. A., Wong, R., Hsia, K., Pilcher, M., and Stempien, M. J. (1998). Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients. J. Clin. Invest., 101(2), 497–502.CrossRefGoogle ScholarPubMed
Spector, S. A., Hsia, K., Crager, M., Pilcher, M., Cabral, S., and Stempien, M. J. (1999). Cytomegalovirus (CMV) DNA load is an independent predictor of CMV disease and survival in advanced AIDS. J. Virol., 73(8), 7027–7030.Google ScholarPubMed
Speir, E., Modali, R., Huang, E. S.et al. (1994). Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science, 265(5170), 391–394.CrossRefGoogle ScholarPubMed
Speir, E., Shibutani, T., Yu, Z. X., Ferrans, V., and Epstein, S. E. (1996). Role of reactive oxygen intermediates in cytomegalovirus gene expression and in the response of human smooth muscle cells to viral infection. Circ. Res., 79(6), 1143–1152.CrossRefGoogle ScholarPubMed
Stagno, S., Reynolds, D. W., Tsiantos, A., Fuccillo, D. A., Long, W., and Alford, C. A. (1975). Comparative serial virologic and serologic studies of symptomatic and subclinical congenitally and natally acquired cytomegalovirus infections. J. Infect. Dis., 132(5), 568–577.CrossRefGoogle ScholarPubMed
Streblow, D. N., Soderberg-Naucler, C., Vieira, J.et al. (1999). The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell, 99(5), 511–520.CrossRefGoogle ScholarPubMed
Talarico, C. L., Burnette, T. C., Miller, W. H.et al. (1999). Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob. Agents Chemother., 43(8), 1941–1946.Google ScholarPubMed
The, T. H., , B. W., Berg, A. P., van der Giessen, M.et al. (1990). Cytomegalovirus antigenemia. Rev. Infect. Dis., 12 Suppl. 7, S734–S744.CrossRefGoogle ScholarPubMed
Valantine, H. A., Gao, S. Z., Menon, S. G.et al. (1999). Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study. Circulation, 100(1), 61–66.CrossRefGoogle ScholarPubMed
Wagner, J. A., Ross, H., Hunt, S.et al. (1995). Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation. Transplantation, 60(12), 1473–1477.CrossRefGoogle ScholarPubMed
Whitcup, S. M., Fortin, E., Lindblad, A. S.et al. (1999). Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis. J. Am. Med. Assoc., 282(17), 1633–1637.CrossRefGoogle ScholarPubMed
Winston, D. J. and Busuttil, R. W. (2004). Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors. Transplantation, 77(2), 305–308.CrossRefGoogle ScholarPubMed
Winston, D. J., Ho, W. G., Bartoni, K.et al. (1993). Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled double-blind trial. Ann. Intern. Med., 118(3), 179–184.CrossRefGoogle ScholarPubMed
Winston, D. J., Wirin, D., Shaked, A., and Busuttil, R. W. (1995). Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients. Lancet, 346(8967), 69–74.CrossRefGoogle ScholarPubMed
Winston, D. J., Yeager, A. M., Chandrasekar, P. H., Snydman, D. R., Petersen, F. B., and Territo, M. C. (2003). Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Clin. Infect. Dis., 36(6), 749–758.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×