Rising antigenemia levels may be misleading in pre-emptive therapy of human cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients

Background and objectives: Hematopoietic stem cell transplant (HSCT) recipients after show rising levels of antigenemia during pre-emptive ganciclovir treatment of human cytomegalovirus (HCMV) infection. This raises some doubts about the therapeutic decisions to be taken. Design and methods: Three groups of HSCT recipients with HCMV infection undergoing anti-viral treatment were identified: group A, showing increasing antigenemia and decreasing viremia and DNAemia; group B, with simultaneous increases in antigenemia, viremia, and DNAemia; and group C, with decreasing levels of all 3 viral markers. Viral load, determined as levels of antigenemia, viremia and DNAemia, was monitored for 3 months post-transplantation in all groups. Results: Group A HSCT recipients showed antigenemia peaks 2-11 days after the onset of treatment, reaching negative levels only 25-30 days thereafter, whereas viremia and DNAemia started to drop earlier. Group B patients, mainly including HSCT recipients with grade II-IV acute GvHD treated with steroids prior to and during antiviral treatment, showed increasing levels of all three viral parameters until 5-10 days after the start of treatment; the levels dropped to negative values 25-30 days thereafter. Group C patients, who acted as controls, progressively cleared virus from blood as an early result of antiviral therapy. Interpretation and conclusions: Antigenemia is not the best assay to guide pre-emptive therapy. Group A patients, who have an isolated increase of antigenemia, do not require a change of the ongoing antiviral therapy. Whether better control of infection could be obtained in group B patients by either reducing immunosuppressive therapy (when possible) or adopting combination therapy remains to be determined.