[CO-CURE] MED: Antiviral Drugs and HHV-6

[Guest guest]

[Moderator's note:

Patients who want to follow the advice given in this post

and provide their doctor with information on antiviral

drugs may also want to include material found here:

http://listserv.nodak.edu/scripts/wa.exe?A2=ind0204C&L=co-cure&P=R3740

http://listserv.nodak.edu/scripts/wa.exe?A2=ind0204C&L=co-cure&P=R1327

http://listserv.nodak.edu/scripts/wa.exe?A2=ind0203A&L=co-cure&P=R2006

http://listserv.nodak.edu/scripts/wa.exe?A2=ind0203A&L=co-cure&P=R153

and be aware of possibly conflicting information, such as:

http://listserv.nodak.edu/scripts/wa.exe?A2=ind0202D&L=co-cure&P=R2516

http://www.chronicillnet.org/reports/ci_report_6.html#anchor120012

Other related information can be found by searching for HHV

in the Co-Cure search engine at:

http://listserv.nodak.edu/scripts/wa.exe?S1=co-cure ]

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Posted on behalf of Jan van Roijen j.van.roijen@...>

From: sezar99q@...

Antiviral Drugs and HHV-6 is a challenging area

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The high incidence of ME patients testing positive for

HHV-6

infection make these reports and observations very relevant

to the search of drugs that have a significant effect in

our disease.

This report suggests Valtrex as having significant benefit

for Herpes virus infected patients and this is consistent

with its recommendation by CCID for Stealth virus infected

patients.

Foscarnet is rated as perhaps having the highest degree of

action against these viruses but with the precaution of

also a much higher rate of serious adverse events.

I suggest that all patients should provide your physicians

information such as this, from leading investigators, to

assist in your search for therapeutics and treatment.

Quintero sezar99q@...>

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Antiviral Drugs and HHV-6

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from the Wisconsin Viral Research Group

http://www.wisconsinlab.com/drugs.htm

Sensitivity of HHV-6 to Antiviral Agents

Data concerning the sensitivity of HHV-6 replication to

antiviral agents is inconsistent. Investigators studying

this subject use different laboratory-adapted strains of

virus, different cell culture media, and different viral

detection systems for measurement, which results in the

generation of conflicting data. In order to obtain

definitive information, using clinical isolates of both

virus variants (HHV-6A and HHV-6B) in cell culture systems

that accurately provide a quantitative measurement of the

inhibition of viral replication is essential. We have

successfully developed and used such cell culture assay

systems.

The following is a summary of our laboratory data and other

published information pertaining to the susceptibility of

HHV-6 to suppression by various antiviral agents.

Ganciclovir is the only drug that has demonstrated its

ability to successfully treat brain infections by HHV-6.

However, it must be administered intravenously and can have

serious side effects. At the present time, the most

promising orally administered drug with respect to the

treatment of HHV-6 infections is VALTREX (acyclovir

prodrug), which has been shown to prevent HHV-6 associated

illness in bone marrow transplant recipients. The use of

Valtrex to treat ongoing, established HHV-6 infections has

not been described in the scientific literature.

Summary of Antiviral Agents

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Beta Interferon AVONEX or BETASERON

Interferons are used to treat certain types of cancer,

chronic infections (e.g. Hepatitis C) and other diseases of

infectious or autoimmune origin such as multiple sclerosis.

Interferon also has known antiviral properties.

Studies by our laboratory, in collaboration with

nvestigators at the Pathogenesis Corporation in Seattle,

Washington, have shown that strains of HHV-6 are sensitive

to suppression by beta interferon. This finding is

consistent with the known antiviral activity of interferon.

However, our laboratory's data indicate that the current

dosage regimens (for MS patients) produce serum levels of

the drug capable of suppressing the replication of HHV-6 by

less than 50%. This modest suppression may be important

when beta interferon therapy is used in conjunction with

another type of antiviral agent. Dual Antiviral Drug

Therapy for Herpesvirus Infections.

Ganciclovir CYTOVENE

Ganciclovir is a drug used to treat CMV retinitis. It is

available in both oral and intravenous forms. Studies have

shown that HHV-6 replication is effectively suppressed by

intravenous ganciclovir and the drug has been used to

successfully treat life-threatening HHV-6 infections of the

brain and spinal cord in bone marrow transplant recipients.

Treatment with intravenous ganciclovir may cause

potentially serious side effects, most commonly bone marrow

suppression. Oral ganciclovir is available, but it produces

relatively low serum levels of the drug and is unlikely to

be highly

effective against established HHV-6 infections.

Roche Laboratories has developed a new formulation of oral

ganciclovir called ProGAN. It appears to achieve serum

levels of the drug that are equivalent to those obtained

with intravenous therapy. Currently being studied as a

treatment of cytomegalovirus retinitis in patients with

AIDS, it may be available within the next one or two

years.

Acyclovir ZOVIRAX

Acyclovir is used to treat herpes simplex (HSV), varicella

zoster (VZV) infections. It is available in oral form.

Available data indicate that HHV-6 is relatively

insensitive to the inhibitory effects of acyclovir. The

mean inhibitory concentration 50% (IC50) of acyclovir for

HHV-6 strains is approximately 30 uM, a concentration well

above the plasma levels achievable with either oral or

intravenous therapy.

Acyclovir VALTREX

Valacyclovir or VALTREX is an orally delivered drug chiefly

used to treat HSV and VZV. It is a prodrug of acyclovir,

meaning that it is converted to active acyclovir within the

body. This results in higher levels of drug in the blood

stream and it is believed that this level of drug might be

partially effective against HHV-6. Valacyclovir has been

used to effectively decrease the incidence of HHV-6

associated disease in bone marrow transplant recipients.

Thus it is effective against reactivation of HHV-6, but may

not be effective in suppressing an active, chronic

infection.

Studies have also demonstrated that VALTREX therapy at

standard dosages is associated with a low rate of adverse

side effects. Thus, VALTREX treatment stands as a potential

alternative for long-term therapy for HHV-6 associated

diseases especially in combination with another antiviral

drug such as beta interferon.

Foscarnet FOSCAVIR

Foscarnet is used to treat CMV retinitis. The literature

concerning the sensitivity of HHV-6 replication to

suppression by foscarnet is quite consistent in that all

virus strains tested showed marked sensitivity to the drug.

However, treatment with intravenous foscarnet carries with

it a significant risk of toxicity, which most commonly

manifests as renal dysfunction and electrolyte imbalances.

Cidofovir VISTIDE or (S)-HPMPC

Cidofovir is used to treat CMV retinitis is patients with

AIDS. Intravenous administration of cidofovir can be

associated with significant renal toxicity, although it

appears to be less toxic than either foscarnet or

ganciclovir.

Cidofovir is available for use in off-label applications,

such as the treatment of HHV-6 associated disease. Two cell

culture based studies have reported that cidofovir can

effectively suppress the replication of HHV-6, although

this observation has not been confirmed by other

investigators.

Non-conventional Antiviral Agents

Several preparations of various types have been assessed

for their ability to suppress the replication of HHV-6 in

cell culture. The potential for these agents to be used in

the clinical setting remains unclear, and little or nothing

is known concerning their pharmokinetics or the plasma

levels they can achieve.

One of these is Ampligen, approved for use in Canada and

Belgium, but not in the U.S. The Ampligen web site states

that results of trials in the U.S. and Belgium " suggest

that Ampligen may be an effective treatment for a certain

subset of Myalgic Encephalomyelitis (ME)/Chronic Fatigue

Syndrome (CFS) patients, namely those with severe

debilitation. " The structure of this drug is similar to a

known interferon inducer and this strongly suggests that

any suppressive effect Ampligen may have on HHV-6

replication is mediated

by interferon. Ampligen is a synthetic, mismatched,

double-stranded RNA, and a single report of its ability to

inhibit HHV-6 replication has been published. Recent

reports from some patients are conflicting, and the value

of Ampligen in the treatment of CFS remains to be

determined.

Recently, transfer factor has been mentioned as a means of

combating viral infections, including HHV-6. Transfer

factor is in the colostrum present in mother's milk the

first few days after delivery of a newborn. It is known to

stimulate the immune system's " memory " and therefore help

the body's own defenses increase their ability to fight

infection naturally. Because transfer factor is not species

specific, it is now being made in cows and processed for

human use.

Additional information about transfer factor is readily

available on the Internet. Its effectiveness against HHV-6

is currently being studied by other investigators.

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Copyright © 2002 Wisconsin Viral Research Group, Ltd

http://www.wisconsinlab.com/drugs.htm

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