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Previous Volume 340:1063-1070 April 8, 1999 Number 14 Next

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ABSTRACT

Background The intraocular ganciclovir implant is effective for local treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS), but it does not treat or prevent other systemic manifestations of cytomegalovirus infection.

Methods Three hundred seventy-seven patients with AIDS and unilateral cytomegalovirus retinitis were randomly assigned to one of three treatments: a ganciclovir implant plus oral ganciclovir (4.5 g daily), a ganciclovir implant plus oral placebo, or intravenous ganciclovir alone. The primary outcome measure was the development of new cytomegalovirus disease, either contralateral retinitis or biopsy-proved extraocular disease.

Results The incidence of new cytomegalovirus disease at six months was 44.3 percent in the group assigned to the ganciclovir implant plus placebo, as compared with 24.3 percent in the group assigned to the ganciclovir implant plus oral ganciclovir (P=0.002) and 19.6 percent in the group assigned to intravenous ganciclovir alone (P<0.001). As compared with placebo, oral ganciclovir reduced the overall risk of new cytomegalovirus disease by 37.6 percent over the one-year period of the study (P=0.02). However, in the subgroup of 103 patients who took protease inhibitors, the rates of new cytomegalovirus disease were low and of similar magnitude, regardless of treatment assignment. Progression of retinitis in the eye that initially received an implant was delayed by the addition of oral ganciclovir, as compared with placebo (P=0.03). Treatment with oral or intravenous ganciclovir reduced the risk of Kaposi's sarcoma by 75 percent (P=0.008) and 93 percent (P<0.001), respectively, as compared with placebo.

Conclusions In patients with AIDS and cytomegalovirus retinitis, oral ganciclovir in conjunction with a ganciclovir implant reduces the incidence of new cytomegalovirus disease and delays progression of the retinitis. Treatment with oral or intravenous ganciclovir also reduces the risk of Kaposi's sarcoma.

Source Information

From the Department of Ophthalmology, Emory University School of Medicine, Atlanta (D.F.M.); the Department of Ophthalmology, University of California, Irvine (B.D.K.); Kaiser Permanente, San Francisco (R.A.W.); Georgetown University, Washington, D.C. (A.G.P.); and Roche Global Development, Palo Alto, Calif. (H.L., C.A.R.).

Address reprint requests to Dr. Martin at the Emory University School of Medicine, Department of Ophthalmology, 1365B Clifton Rd., N.E., Atlanta, GA 30322, or at dmart04{at}emory.edu.

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• Lagunoff, M., Lukac, D. M., Ganem, D. (2001). Immunoreceptor Tyrosine-Based Activation Motif-Dependent Signaling by Kaposi's Sarcoma-Associated Herpesvirus K1 Protein: Effects on Lytic Viral Replication. J. Virol. 75: 5891-5898 [Abstract] [Full Text]  
• Polson, A. G., Huang, L., Lukac, D. M., Blethrow, J. D., Morgan, D. O., Burlingame, A. L., Ganem, D. (2001). Kaposi's Sarcoma-Associated Herpesvirus K-bZIP Protein Is Phosphorylated by Cyclin-Dependent Kinases. J. Virol. 75: 3175-3184 [Abstract] [Full Text]  
• Girard, P.-M. (2001). Discontinuing Pneumocystis carinii Prophylaxis. NEJM 344: 222-223 [Full Text]  
• Kempen, J. H., Jabs, D. A., Dunn, J. P., West, S. K., Tonascia, J. (2001). Retinal Detachment Risk in Cytomegalovirus Retinitis Related to the Acquired Immunodeficiency Syndrome. Arch Ophthalmol 119: 33-40 [Abstract] [Full Text]  
• Purdy, B. D. (2000). Management and Prevention of Opportunistic Infections in the HIV-Infected Patient. Journal of Pharmacy Practice 13: 475-498 [Abstract]  
• Chan, S. R., Chandran, B. (2000). Characterization of Human Herpesvirus 8 ORF59 Protein (PF-8) and Mapping of the Processivity and Viral DNA Polymerase-Interacting Domains. J. Virol. 74: 10920-10929 [Abstract] [Full Text]  
• Samaniego, F., Pati, S., Karp, J. E., Prakash, O., Bose, D. (2000). Human Herpesvirus 8 K1-Associated Nuclear Factor-kappa B-Dependent Promoter Activity: Role in Kaposi's Sarcoma Inflammation?. J Natl Cancer Inst Monogr 2000: 15-23 [Abstract] [Full Text]  
• Ma, H. J., Sjak-Shie, N. N., Vescio, R. A., Kaminsky, M., Mikail, A., Pold, M., Parker, K., Beksac, M., Belson, D., Moss, T. J., Wu, C. H., Zhou, J., Zhang, L., Chen, G., Said, J. W., Berenson, J. R. (2000). Human Herpesvirus 8 Open Reading Frame 26 and Open Reading Frame 65 Sequences from Multiple Myeloma Patients: A Shared Pattern Not Found in Kaposi's Sarcoma or Primary Effusion Lymphoma. Clin. Cancer Res. 6: 4226-4233 [Abstract] [Full Text]  
• Kovacs, J. A., Masur, H. (2000). Prophylaxis against Opportunistic Infections in Patients with Human Immunodeficiency Virus Infection. NEJM 342: 1416-1429 [Full Text]  
• Kirshner, J. R., Lukac, D. M., Chang, J., Ganem, D. (2000). Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 57 Encodes a Posttranscriptional Regulator with Multiple Distinct Activities. J. Virol. 74: 3586-3597 [Abstract] [Full Text]  
• Antman, K., Chang, Y. (2000). Kaposi's Sarcoma. NEJM 342: 1027-1038 [Full Text]  
• Gustafson, E. A., Schinazi, R. F., Fingeroth, J. D. (2000). Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir. J. Virol. 74: 684-692 [Abstract] [Full Text]  
• USPHS/IDSA Prevention of Opportunistic Infections, (1999). 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. ANN INTERN MED 131: 873-908 [Full Text]  
• Lukac, D. M., Kirshner, J. R., Ganem, D. (1999). Transcriptional Activation by the Product of Open Reading Frame 50 of Kaposi's Sarcoma-Associated Herpesvirus Is Required for Lytic Viral Reactivation in B Cells. J. Virol. 73: 9348-9361 [Abstract] [Full Text]  
• Holland, G. N. (1999). Treatment Options for Cytomegalovirus Retinitis: A Time for Reassessment. Arch Ophthalmol 117: 1549-1550 [Full Text]  
• VELEZ, G., WHITCUP, S. M (1999). New developments in sustained release drug delivery for the treatment of intraocular disease. Br J Ophthalmol 83: 1225-1229 [Full Text]  
• (1999). Ganciclovir Implant, Oral Therapy for CMV Retinitis. JWatch Infect. Diseases 1999: 3-3 [Full Text]  
• Masur, H., Kaplan, J. (1999). Does Pneumocystis carinii Prophylaxis Still Need to Be Lifelong?. NEJM 340: 1356-1358 [Full Text]  
• Whitley, R. J., Holland, G. N. (1999). Cytomegalovirus Retinitis -- Evolving Therapies in a New Era. NEJM 340: 1108-1110 [Full Text]