HHV6 therapy in CFS patients

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CFS patients with active infection by HHV-6 (variants A or B) can be treated with antivirals or immune modulatory agents in order to relieve the symptoms of fatigue and minimize CNS complaints. Acyclovir has remained the gold standard of treatment for herpes viral infections in general. However, pilot studies using acyclovir and ganciclovir showed persistence of HHV-6 variant A in spinal fluid even after treatment (Peterson, unpublished studies). HHV-6 does not encode thymidine kinase, and thus is not highly sensitive to acyclovir and its analogs (Gomples et al., 1995). Non-guanosine derivatives, however, have been shown in vitro to be of greater efficacy against HHV-6 specifically. De Clercq et al. (2001) demonstrated increased efficacy of the non-guanosine compounds S2242, cidofovir, and foscarnet, both in T lymphoblast cells, and in fresh blood lymphocytes, though it should be noted that only foscarnet and cidofovir are commercially available. Cidofovir, the first nucleotide analog available for clinical use, is highly active against CMV and demonstrates activity against HHV-6 as well in vitro. Cidofovir also has a substantially more favorable administration and side-effect profile. Current pilot studies are being conducted with cidofovir in a standard dosage of 5 mg/kg intravenously for patients positive for HHV-6 in their spinal fluid, as detected by two different tests (PCR and tissue culture). Preliminary results suggest that HHV-6 infection is suppressed by cidofovir, but recurs when treatment is stopped. In a recent case study, acute infection by HHV-6 variant A in the CNS of an immunocompetent adult was successfully treated with cidofovir and ganciclovir (Denes et al., 2004).

The only herpesvirus vaccine licensed for human use in the United States is for VZV, thus this preventive strategy is not available for the clinician treating HHV-6 patients. HSV-1, HSV-2, and EBV vaccines are in development and a specific HHV-6 vaccine could be forthcoming as well.

Antiviral therapies that have been employed for CFS patients who demonstrate evidence of persistent peripheral and CNS infection include Poly I: Poly C12U, isoprinosine, ganciclovir, foscarnet, and cidofovir. Valacyclovir (a prodrug of acyclovir) and ganciclovir were found not to result in prolonged viral remission, and oral antiviral therapy (such as acylcovir and famvir) has yielded minimal results. Parenteral antiviral therapies have concentrated on patients who demonstrate severe disabling fatigue and prominent CNS clinical complaints and immune dysfunction. Neither oral nor parenteral therapy has been studied in rigorous double-blind placebo-controlled studies.

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