Differential susceptibility of adenovirus clinical isolates to cidofovir and ribavirin is not related to species alone

Antivir Ther. 2009;14(1):55-61.


Background: We have previously reported that human adenovirus (HAdV) reference strains clearly show species-dependent resistance to ribavirin, whereas different species of HAdV are equally sensitive to cidofovir. All the serotypes tested were susceptible to cidofovir, whereas only serotypes from species C were sensitive to ribavirin. Here, we aimed to extend these investigations to clinical isolates.

Methods: In vitro, we tested 126 isolates obtained from 65 patients included in a European survey of HAdV infection.

Results: Among the 126 isolates tested, all presented cidofovir 50% inhibitory concentration (IC50) in the same range as the HAdV 5 reference strain. Regarding ribavirin, all isolates from species C (79 tested) showed an IC50 comparable with previously reported results for reference strains; however, 24/32, 2/6 and 3/3 tested isolates from species A, B and D, respectively, were shown to have a ribavirin IC50 comparable with the HAdV 5 reference strain (species C), contrary to previous observations for reference strains of the same species. Among patients who were treated with cidofovir for disseminated HAdV infection, > or = 4 sequential isolates could be obtained from 9 patients; no variation in cidofovir susceptibility could be detected.

Conclusions: Cidofovir is active in vitro in all HAdV clinical isolates. Ribavirin was revealed to be active on most HAdV isolates from species A, B and D, and in all isolates from species C. Finally, no resistance to cidofovir became apparent in sequential isolates obtained from treated patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / drug effects*
  • Adenoviridae / genetics
  • Adenoviridae / isolation & purification
  • Adenovirus Infections, Human / drug therapy
  • Adenovirus Infections, Human / virology
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line, Tumor
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Cytosine / therapeutic use
  • DNA, Viral / genetics*
  • Drug Resistance, Viral*
  • Genotype
  • Humans
  • Organophosphonates / pharmacology*
  • Organophosphonates / therapeutic use
  • Ribavirin / pharmacology*
  • Ribavirin / therapeutic use
  • Serotyping
  • Species Specificity


  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Ribavirin
  • Cytosine
  • Cidofovir