The dynamics of human cytomegalovirus replication in vivo

Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-co mpetitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intr avenous ganciclovir; (b) those in whom ganciclovir-resistant strains appear ed during long-term therapy; and (c) those in whom ganciclovir-resistant st rains disappeared with alternative drug therapy. In all cases, it was possi ble to provide accurate estimates of the doubling time of CMV and its half- life of disappearance after antiviral chemotherapy. The results from all th ree approaches demonstrated that the doubling time/half-life of CMV in bloo d is similar to 1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemoth erapy needed for the effective treatment of this important human pathogen.