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Clinical Trial
. 2009 Nov;83(22):11857-61.
doi: 10.1128/JVI.01005-09. Epub 2009 Sep 9.

Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers

Yo Hoshino  1 , Harutaka Katano, Ping Zou, Patricia Hohman, Adriana Marques, Stephen K Tyring, Dean Follmann, Jeffrey I Cohen
Affiliations
Clinical Trial

Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers

Yo Hoshino et al. J Virol. 2009 Nov.

Abstract

Epstein-Barr virus (EBV) establishes a latent infection in B cells in the blood, and the latent EBV load in healthy individuals is generally stable over time, maintaining a "set point." It is unknown if the EBV load changes after long-term antiviral therapy in healthy individuals. We treated volunteers with either valacyclovir (valaciclovir) or no antiviral therapy for 1 year and measured the amount of EBV DNA in B cells every 3 months with a novel, highly sensitive assay. The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P = 0.86). The difference in the slopes of the lines for the number of EBV-infected B cells over time for the valacyclovir group versus the control group approached significance (P = 0.054). In contrast, the number of EBV DNA copies per B cell remained unchanged in both groups (P = 0.62 and P = 0.92 for the control and valacyclovir groups, respectively). Valacyclovir reduces the frequency of EBV-infected B cells when administered over a long period and, in theory, might allow eradication of EBV from the body if reinfection does not occur.

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Figures

FIG. 1.
FIG. 1.
EBV-positive cells per 105 B cells over time and linear regression lines for the first three subjects from the valacyclovir (A) and control (B) groups. Each symbol connected with a broken line represents data for one subject. Solid lines associated with symbols indicate linear regression lines of the data for each subject.
FIG. 2.
FIG. 2.
Rate of change (slope) in the number of EBV-infected B cells over time. (A) Linear regression lines for individual control subjects (left) and valacyclovir (VACV) patients (right) are shown as thin lines. Thick gray lines indicate the mean slope for each group. (B) The individual slopes for each control subject (circles) and valacyclovir patient (triangles) are depicted. Short horizontal bars indicate means, and vertical bars indicate standard errors (S.E.).
FIG. 3.
FIG. 3.
Mean EBV DNA copies per B cell over time. (A) Linear regression lines for individual control subjects (left) and valacyclovir (VACV) patients (right) are shown as thin lines. Thick gray lines indicate the mean slope for each group. (B) The individual slopes for each control subject (circles) and valacyclovir patient (triangles) are depicted. Short horizontal bars indicate means, and vertical bars indicate standard errors (S.E.).
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