Current Management of Cytomegalovirus Disease in Patients with AIDS

Abstract

Cytomegalovirus (CMV) infection is common in both homosexual and heterosexual HIV-infected patients, and causes disease in a substantial proportion of patients with AIDS and very low CD4+ cell counts. Both ganciclovir, an analog of the nucleoside guanosine, and foscarnet, an analog of pyrophosphate, are licensed for treatment of CMV retinitis. They may also have a role in the treatment of gastrointestinal disease caused by CMV. In the Studies of Ocular Complications of AIDS comparative trial the two agents were equally effective against CMV retinitis, but patients receiving foscarnet had significantly longer survival, even after adjusting for covariates including antiretroviral therapy. Ongoing studies are evaluating higher dosages of foscarnet for maintenance therapy and combined therapy with ganciclovir and foscarnet. Tolerance of ganciclovir therapy has been facilitated by adjunctive therapy with colony-stimulating factors. Because both ganciclovir and foscarnet must be administered by intravenous infusion and are associated with significant toxicities, other anti-CMV agents are under active development, including HPMPC and an oral formulation of ganciclovir. Management of CMV retinitis involves individualizing therapy, balancing side effects and administration requirements, and, in many clinical settings, the overall cost of treatment.

Inhibition of Human Cytomegalovirus DNA Maturation by a Benzimidazole Ribonucleoside Is Mediated through the UL89 Gene Product

“…The clinically available drug therapies for treating HCMV disease include the viral DNA polymerase inhibitors ganciclovir (Cytovene), foscarnet sodium (Foscavir), and cidofovir (Vistide). These all have low oral bioavailability and/or dose-related toxicities (26,32) which limit their usefulness, particularly in AIDS patients on antiretroviral therapies. Additionally, resistance to ganciclovir and foscarnet sodium in this patient group has been correlated with clinical failure (20).…”

Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication in monocytes: possible role of endogenous interleukin-8

“…However, HCMV is one of the most frequent opportunistic agents causing severe illness in immunocompromised hosts, including human immunodeficiency virus type 1 (HIV-1)-infected patients (25,26). HCMV clinical manifestations, often at unusual body sites, are very common in the advanced stages of HIV infection, and up to 90% of AIDS patients display signs of disseminated HCMV infection at autopsy (47).…”

The Genetic Basis of Human Cytomegalovirus Resistance and Current Trends in Antiviral Resistance Analysis

“…Nonetheless, they have been shown to be effective for the treatment of CMV infections. In SOT, HSCT, and acquired immunodeficiency syndrome (AIDS) patients, GCV has been shown to reduce the severity of CMV retinitis, gastrointestinal disease, and, to a lesser extent, pneumonia [15]. PFA has also been reported to be effective for treatment of CMV infections in patients with AIDS [16], and has been used for treatment of GCV-resistant CMV infections.…”