This study was designed to determine safety and efficacy of a 6-month trial of
valacyclovir in single-virus Epstein-Barr virus (EBV)
persistent infection. Phase I of this study used four specific criteria to define a subset of patients with
chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress
radionuclide ventriculographic (RVG) examinations pre- and posttreatment with
valacyclovir. In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum
IgM antibody titers to EBV viral capsid
antigen and/or total diffuse early
antigen as measured by the
enzyme-linked
immunosorbent assay method. The treatment group comprised 10 CFS patients with no serum
antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum
antibodies (
IgG) to conformational structural
antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received
valacyclovir 1.0-1.5 gm q.6.h. for 6 months. This
valacyclovir dose achieved serum
acyclovir C(max) of > 7 microm and high
antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study. The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating
valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient's functional capacity at baseline and after 1, 3 and 6 months of
valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed. In the second phase, left ventricular dynamics were repeated after 6 months of treatment with
valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-
persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with
valacyclovir. Nine CFS patients with EBV/human cytomegalovirus
co-infection did not benefit from 6 months of similar treatment.
Valacyclovir is not an effective anti-human cytomegalovirus
antiviral drug. Unimproved CFS patients with
co-infections EBV and human cytomegalovirus may require combined treatment with
valacyclovir and another
drug more active against human cytomegalovirus. This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.