Information on other treatments that have had limited success in the management of HHV-6:
Isoprinosine is a synthetic purine derivative licensed in 1971 that exhibits both immune modulating and antiviral properties. Isoprinosine modulates T cell and NK function (Diaz-Mitoma et al., 2003). Isoprinosine did not exhibit side effects in safety studies or post-marketing experience (Diaz-Mitoma et al, 2003). Isoprinosine has been used by physicians in Europe for CFS patients with evidence of active HHV-6 infection, although no in vitro efficacy studies have been done specifically for HHV-6 infections.
Isoprinosine is not currently available in the United States but is used widely in Eastern Europe as an antiviral/immunomodulator and as a adjunctive therapy for cancer. Americans can import it legally for personal use.
Ampligen is a mismatched double-stranded RNA with broad antiviral and immunomodulatory properties produced by Hemispherx Biopharma, Inc. Hemispherx recently completed Phase III trials for Ampligen as a treatment for CFS and is currently pursuing FDA approval of the product. In a 1994 study, Ampligen was found to inhibit replication of HHV-6A in in-vitro testing at concentrations of 100 and 200 pg/ml (Ablashi, Berneman et al 1994). When the Ampligen was removed from the virus-infected cell culture, HHV-6 infection reappeared slowly but never reached the same level as before. No toxicity of the cells was noted. In a 1995 randomized, double-blinded placebo controlled study (Strayer et al) of CFS patients, patients on Ampligen had improved Karnofsky performance scores, increased capacity for daily living (ADL), reduced cognitive impairment and improved work on the treadmill. Patients on Ampligen also required less medication to control their symptoms.
In 1994, Sudaholnik evaluated the 2-5A and RNAase L levels in 15 CFS patients before and after Ampligen treatment compared to healthy controls. Patients had lower levels of 2-5A and increased levels of RNAase L activity. Therapy with Ampligen resulted in significant downregulation of the 2-5A/RNAase L pathway. Also the levels of HHV-6 replication in PBMCs significantly decreased after treatment. For additional information regarding Ampligen, please refer to: http://www.hemispherx.net/content/rnd/drug_candidates.htm
HHV-6 infection induces production of certain cytokines from infected macrophages which play a role in controlling and containing the viral infection (Inoue et al, 1993). One of these cytokines, interferon, has broad antiviral properties and has been shown to have in vitro activity against HHV-6 infections.
However there is little information regarding treatment of HHV-6 with any of the three types of interferon. Treatment with alpha interferon has contributed to improved quality of life scores in CFS patients (See & Tilles, 1996). Interferon beta has been used to treat MS patients for over 20 years as it has shown effectiveness in decreasing the progression of the disease and reducing disability (Fillipini, 2003), particularly with relapsing/remitting MS.
One group demonstrated in vitro that interferon beta at concentrations of 0.5 ug/ml reduced the replication of HHV-6 in a line of T cells. Additionally, they examined the sera of MS patients treated with interferon beta compared to control MS patients and found that the treatment group had reduced levels of HHV-6 DNA and lower levels of IgM antibody reactivity. The group also noted that the sera obtained after treatment showed decreased levels of HHV-6 DNA as compared to the pretreatment sera. Another study (Alvarez-Lafuente, 2004) evaluated 105 patients with relapsing/remitting who were treated with interferon beta, and compared them to similar patients who were not treated and found that the viral load was twice as high by quantitative PCR in the untreated patients versus the treated cases. These effects were only seen during relapse; no differences were seen when patients were in remission. Additionally, all cases of HHV-6 were variant A. Thus, interferon beta may exert some of the same antiviral properties exhibited in HHV-6 treatment as for MS.
Interferon therapy is associated with several adverse effects including fever, fatigue, myalgia, nausea, and headache, among others (Fillipini, 2003).