Real‐Time Blood Plasma Polymerase Chain Reaction for Management of Disseminated Adenovirus Infection

Abstract

We evaluated the usefulness of quantifying blood plasma adenovirus DNA loads for the management of adenovirus infection. Quantification of adenovirus A, B, and C DNA loads was done with real-time polymerase chain reaction (PCR) assays. Blood plasma specimens obtained from 44 immunocompromised patients were screened prospectively with this method. PCR findings for 36 patients were negative, and none of the patients developed disseminated adenoviral disease. PCR findings for 8 patients were positive; all 8 had invasive adenoviral disease and were treated with cidofovir. Sequential measurements of adenovirus DNA loads were performed to monitor the effect of cidofovir therapy. Decrease in the blood plasma DNA load was significantly higher in patients with a good response to cidofovir than in patients with a poor response and was therefore correlated with survival. Detection of adenovirus DNA in blood plasma appears to be useful for identifying patients at risk for invasive disease. Moreover, quantification of adenovirus DNA loads in plasma is helpful for monitoring the efficacy of antiviral therapy.

Safe adoptive transfer of virus‐specific T‐cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation

“…Current antiviral agents are often limited by weak activity against adenovirus and by side effects, including suppression of bone-marrow function and renal toxicity (Bordigoni et al, 2001;Gavin & Katz, 2002;Ljungman et al, 2003;Lankester et al, 2004;Leruez-Ville et al, 2004).…”

Advances in the management of disseminated adenovirus disease in stem cell transplant recipients: impact of adenovirus load (DNAemia) testing

“…As cidofovir had a broader range of activity against different HAdV types and clinical isolates, a multitude of case reports and noncontrolled studies on its use have been published. Although both recovery and treatment failures have been reported for both cidofovir [1][2][3]16,17] and ribavirin [3,4], more clinical experience has been gained with cidofovir. CMX001, a prodrug of cidofovir, has a higher in vitro activity against HAdV and is less nephrotoxic than cidofovir.…”

“…Another study identified high peak HAdV loads before treatment and a longer interval between onset of symptoms and start of therapy as risk factors for failure of cidofovir therapy [17].…”

“…A report concerning cidofovir treatment of disseminated HADV disease revealed that 'responders' to cidofovir had median decreases of 1.4 log 10 and 3.0 log 10 after the first and second cidofovir infusions, respectively, whereas 'nonresponders' showed no or only a very low median decrease of 0.0 log 10 copies/ml and 0.8 log 10 copies/ml, respectively, and were at high risk of a fatal outcome [17]. However, this study did not include a control group.…”

A case of ‘red eye’ post allogeneic stem cell transplantation

“…Cidovovir has been shown to have in vitro activity against all adenoviral serotypes 3 and data suggests an antiviral effect in certain treated individuals. 4 In contrast, Ribavirin appears to have in vitro activity primarily against subgroup C viruses 3 and this factor may contribute to the limited data supporting the antiviral efficacy of Ribavirin in vivo. 5 In addition to existing antiviral strategies, adoptive immunotherapy using cytotoxic adenovirus-specific T-cells may be a promising future therapeutic alternative.…”