Correlation of cytomegalovirus DNA levels with response to antiviral therapy in cardiac and renal allograft recipients

Background. Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. A rapid, sensitive, specific, and reliable test is desirable for early detection of CMV infection and for monitoring the efficacy of antiviral therapy. Methods. We examined the incidence of CMV infection in 95 cardiac and 25 renal allograft recipients followed for up to 3 years using qualitative and quantitative polymerase chain reaction (PCR) techniques. Results were subsequently correlated with clinical findings. Of the 236 samples analyzed by the CMV PCR, 84 and 20 were also analyzed by blood buffy coat culture and anti-CMV antibody IgM assays, respectively. Results. The sensitivity of the CMV PCR was found to be superior to that of the other assays, although the specificity of the blood buffy coat culture is as good as that of the CMV PCR, which is higher than that of the anti-CMV antibody IgM assay. CMV infection was detected by the CMV PCR in 17 of 95 cardiac and 9 of 25 renal transplant recipients. Clinical symptoms were observed when greater than or equal to 500 copies of CMV DNA/1 mu g of total DNA were detected by a quantitative CMV PCR assay using an external control CMV plasmid; however, some patients had symptoms when 50-100 copies were present. The levels of CMV DNA detected varied (50-1000 copies) in patients who developed asymptomatic CMV infection. The CMV DNA levels decreased to 50-100 copies 1-2 weeks after antiviral therapy was initiated and correlated well with disappearance of clinical symptoms. CMV DNA levels decreased to less than or equal to 5 copies at 4-7 weeks after treatment. This contrasts with patients who were unresponsive to anti-CMV therapy, in whom high levels of CMV DNA (greater than or equal to 500 copies) persisted for at least 5 weeks and significant levels of CMV DNA (50-100 copies) were detected for several months afterward, despite multiple courses of anti-CMV therapy. Clinical symptoms also did not disappear during this period of observation. Conclusions. (1) The CMV PCR represents a rapid, sensitive, specific, reliable test for detection of CMV infection, especially for detection of virus replication in an incipient phase. (2) The quantitative CMV PCR is useful for monitoring the efficacy of antiviral therapy to distinguish patients who respond to therapy from those who do not. (3) CMV DNA levels greater than or equal to 500 copies/1 mu g of total DNA analyzed by the quantitative CMV PCR can be used to differentiate CMV infection from other infections and rejection.