from Detlef Michel, Meike Chevillotte and Thomas Mertens writing in Cytomegaloviruses: From Molecular Pathogenesis to Intervention:
Three drugs are currently used for treatment of human cytomegalovirus (HCMV) disease or infection: ganciclovir (GCV)/valganciclovir (valGCV), cidofovir (CDV), and foscarnet (FOS). They all target the viral DNA polymerase pUL54, thereby inhibiting viral DNA replication. In contrast to antiviral treatment of overt HCMV disease, antiviral prophylaxis and pre-emptive therapy aim at prevention of HCMV disease. All current anti-HCMV compounds cause drug-specific and severe side effects and have been reported to select for clinically relevant drug resistant virus variants. Active systemic HCMV infection can be first asymptomatic or symptoms can be non-specific. Therefore, a reliable and fast diagnosis of active systemic viral infection is needed, based on virological markers. This includes early and quantitative detection of drug resistant HCMV variants. Genotyping will become the method of choice for identification of viral drug resistance, but absolutely requires previous quantitative characterization of the effect of individual and combined mutations on the resistance phenotype. A database has been made available in the www containing all published mutations and according information on the quantitative resistance phenotypes. In view of the many published resistance mutations, the database is a helpful tool to correlate diagnosed mutations in a viral genome with resistance. New compounds to treat HCMV infection and disease are urgently needed. They should ideally combine few adverse effects, good oral bioavailability, the option to treat children in utero, as well as novel mechanisms of action, to possibly reduce selection of resistant virus variants by combination therapy. Some substances should also target early steps of viral infection, thereby inhibiting IE- and E-gene expression in infected cells. Modified and new nucleoside analogues, small-molecule compounds, benzimidazoles, indolocarbazole protein kinase inhibitors as well as drugs with originally other indications (leflunomide, artesunate) will soon augment the HCMV antiviral portfolio. They will expand treatment options, but will also increase the number of resistance-conferring mutations, thereby rendering resistance analyses even more complex.
Further reading: Cytomegaloviruses: From Molecular Pathogenesis to Intervention