Relationship of serum human herpesvirus 6 DNA with cytomegalovirus pp65 antigenemia in allogeneic bone marrow transplant recipients.

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We read with great interest the study by Jacobs et al. (1) regarding human herpesvirus 6 (HHV-6) infection after lung and heart-lung transplantation, where no association between HHV-6 infection and cytomegalovirus (CMV) infection was found. The clinical impact of HHV-6 in the posttransplant setting is still debated (2); a relationship between HHV-6 infection and CMV infection and disease has been demonstrated in transplant recipients (3–4). Cultures of HHV-6 from peripheral blood mononuclear cells (PBMC) and other body fluids reflect active virus replication, yet provides no information to differentiate between active or latent HHV-6 infection. In contrast, the detection of HHV-6 DNA in cell free samples, such as serum or plasma, is associated with active virus replication (5). We investigated whether the presence of HHV-6 DNA in serum was associated with development of CMV pp65 antigenemia following allogeneic bone marrow transplantation (BMT). From March 1999 to August 2000, 40 consecutive BMT recipients at risk for CMV infection (donor and/or recipient were CMV seropositive) were enrolled in the study. Patients were prospectively monitored by CMV pp65 (C10–C11) at weekly intervals, and on suspicion of CMV infection from day −7 to posttransplant day +100. Detection of HHV-6 DNA by nested PCR was performed on serum samples obtained 2, 3, 4, and 6 weeks after BMT by using the Oligo-Mix Nested HHV-6 ORF 13R kit (Amplimedical-Bioline, Italy), which uses primers directed against the ORF 13R region of HHV-6 variant A and B. The lower limit of detection was 10 copies/ml. The variants of the HHV-6 isolates were identified on the basis of restriction fragment length polymorphism (5). As controls, we used sera from 40 BMT donors. 55% of the patients had detectable HHV-6 DNA in serum. Genotype determination performed in 20 patients showed HHV-6 variant B in 11 patients and variant A in 9 patients. PCR failed to detect any HHV-6 DNA in sera from controls. Antigenemia was significantly more frequent in patients with HHV-6 DNA compared to those without. The median peak antigenemia level and the percentages of antigenemia-positive blood samples were significantly higher in patients with HHV-6 DNA than in patients without (Table 1). Clinical characteristics and risk factors for HHV-6 infection did not differ between patients with or without HHV-6 DNA (Table 1).Table 1: Characteristics of BMT recipients with and without HHV-6 DNAThe methods for detecting HHV-6 vary between our study and that of Jacobs et al. (1), making correlation between results uncertain. Of note, the findings of our study compare favorable with those previously reported that have examined the association between active HHV-6 infection and active CMV infection (3–4). However, the results of the studies cannot be directly compared, because HHV-6 and CMV assays, populations, and duration of follow-up differ.