Human Cytomegalovirus Resistance to Antiviral Drugs

Lack of prompt expansion of cytomegalovirus pp65 and IE-1-specific IFNγ CD8+ and CD4+ T cells is associated with rising levels of pp65 antigenemia and DNAemia during pre-emptive therapy in allogeneic hematopoietic stem cell transplant recipients

“…The latter phenomenon, however, has been shown to be a rare event in the allo-SCT setting, at least in treatment-naı¨ve patients. 2,3,5 Our data fully support this assumption. Development of ganciclovir resistance was observed in 2 out of 12 episodes with rising levels of antigenemia subject to analysis.…”

“…Rising levels in antigenemia and DNAemia may also be due to the emergence of ganciclovir-resistant strains; this phenomenon, however, does not seem to be frequent in the allo-SCT setting. 5 The latter pattern was documented earlier in solid-organ transplant recipients experiencing a primary CMV infection and its pathogenetic basis was later elucidated. 6,7 It was shown that persistence of antigenemia in the absence of DNAemia when on ganciclovir treatment was due to overproduction of pp65.…”

Multidrug-resistant cytomegalovirus infection in a pediatric stem cell transplantation patient

“…Resistance of CMV to ganciclovir is mostly caused by mutations within the UL97 gene and less frequently by alterations within the viral UL54 DNA polymerase gene (Gilbert and Boivin, 2005;Lurain and Chou, 2010). Resistance to cidofovir and foscarnet is linked to mutations in the viral DNA polymerase gene.…”

“…Some mutations in and near region III confer dual foscarnet and ganciclovir resistance, and a few mutations (such as A834P and deletion 981-2) confer resistance to the three anti-CMV drugs. Emergence of cidofovir resistance appears to be an extremely rare event and it arises in the clinic following sustained ganciclovir administration (Gilbert and Boivin, 2005;Lurain and Chou, 2010).…”

Differential resistance to antiviral drugs in an immunocompromised patient with cytomegalovirus encephalitis

“…1 Treatment of these HCMV-associated diseases in immunocompromised patients frequently requires long-term use of antiviral agents such as ganciclovir and foscarnet, which may be associated with the emergence of drug-resistant HCMV strains. 2 Here, we describe a 17-year-old Japanese girl who developed refractory immune thrombocytopenic purpura at the age of 4 years. Despite a series of treatments including steroid, intravenous immunoglobulin, vincristine, vinblastine, cyclosporine, azathioprine, splenectomy, and rituximab, her platelet counts remained low, resulting in 2 episodes of intracranial hemorrhage at the age of 12 and in hemoperitoneum at the age of 13.…”