First published on Simmaron Neuroimmune Research Foundation. April 9, 2013 as "Report from Paris: Peterson Reports Antiviral (Vistide) Effective in Treating Herpesvirus Infected Chronic Fatigue Syndrome (ME/CFS) Patients"
“These results show objective endpoints, subset
selection, and recovery. There were complete responders and partial
responders among severely ill CFS patients with HHV6 or CMV. These are
encouraging results for this subset and further well-designed trials should
be pursued to confirm them.” Dr. Dan Peterson.
At the HHV6 Conference in Paris, France today Dr.
Peterson reported on the results of a retrospective study following 65
severely ill chronic fatigue syndrome patients given a course of Vistide
from 2005-2012 for HHV6 and/or HCMV infections. Despite the interest in
pathogens in ME/CFS, antiviral studies are rare and this is the first one
reported for this drug.
Vistide (Cidofovir) gets a lot less press than other
antivirals and immunomodulators (Ampligen, Rituximab, Valcyte, Valtrex)
used in this disorder probably because the drug requires a complex
infusion protocol, frequent blood tests because of the rare but real
possibility of serious kidney side effects, and is expensive
(although it can be covered by insurance).
This combination – infusions, frequent blood tests and
expense – requires close physician follow-up. With Dr. Peterson’s
specialized focus on patients with dysfunctional natural killer cells,
however, he may be most consistent about testing for herpesviruses, which
are known to be active in ME/CFS patients.
After three decades of focusing on immunologically
challenged ME/CFS patients, Peterson may be more experienced at pathogen
detection and treatment than any other practitioner in the field, and so
it’s not surprising to find the first Vistide study coming from his office.
In an interview, a former patient of his said, ‘he leaves no stones
unturned’; when he finds something he goes after it ‘aggressively’.
In his presentation he stated almost 30% of his
patients test positive for HHV-6 or human cytomegalovirus (HCMV) (PCR,
rapid culture, antigenemia), and a whopping 50% test positive for
Epstein-Barr virus (EBNA).
Serious Drug For A Serious Illness
Vistide (Cidofovir) is FDA approved for the treatment of
cytomegalovirus (CMV) in patients with AIDS. (Cytomegalovirus is a member
of the herpesvirus family.) and it’s been used off-label to treat
human papillomavirus, BHK virus, herpes simplex virus, vaccinia virus
infections. The Black Box warning on Vistide speaks for itself:
"Cases of acute renal failure resulting in
dialysis and/or contributing to death have occurred with few as one
or two doses of Vistide. The “recommended dose, rate, frequency of Vistide
injections must not be exceeded.”
A positive response was denoted by a negative pathogen
test, improved fatigue and cognitive functioning determined by an interview
with Dr. Peterson and the patient’s self reports after the trial.
Full Responders - Patients were deemed to be full
responders if they were able to completely return to work or to
Partial Responders – demonstrated significant
improvement of symptoms but were unable to return to work or work related
Non-Responders – Did not demonstrate any measurable
Dr. Peterson reported that seventy percent of patients
were full (able to return to work) or partial (significant increase in
functionality) responders; a very high rate of success in a illness
characterized by a poor response to treatments. Only thirty percent
of Vistide recipients did not have a significantly positive response to the
drug. No serious side effects were seen; ironically the minor side effects
seen were attributed to a drug, Probocenid, used to ensure Vistide was
It’s not clear what percentage of ME/CFS patients will
test positive for HHV6 or cytomegalovirus in other practices but this type
of response suggests the drug may be being under-used. With the FDA
Stakeholder’s meeting coming up in three weeks and the Chronic
Fatigue Initiative’s pathogen discovery study results due to be published
later this year, Dr. Peterson’s presentation is timely. (Unfortunately, Dr.
Peterson was not invited to present at the FDA Stakeholder’s Meeting.)
Dr. Peterson called for placebo-controlled,
double-blinded multi-center studies that address Vistide’s efficacy,
examine its effects on the immune system and study the mechanisms of
increase in VO2 max scores in ME/CFS.
Dr. Peterson reported on several cases, all of whom were
men – something Dr. Peterson has said he likes to do to break up the notion
that only women get this disorder.
A 27-year-old college graduate unable to work
because of constant flu-like symptoms, weakness and marked cognitive
decline (math!) presented with low NK functioning, low VO2 max and HHV6 and
cytomegalovirus infection. He was able to return to work after 24 weeks of
bi-weekly infusions. His VO2 max on the exercise test went up went up 23%,
his NK cells a remarkable 400% and he tested negative for both
viruses at the end of treatment. He had had ME/CFS for three years.
A 54-year-old former high school teacher unable to work
due to extreme fatigue, flu-like symptoms and cognitive problems severe
enough to keep him from being able to grade his students papers presented
with active HHV6 and cytomegalovirus infections and low NK cell functioning
and VO2 max. He was able to return to work after 24 weeks of bi-weekly
infusions. His VO2 max increased 47%, his NK function test went up 20% and
he tested negative for both viruses. He had had ME/CFS for five years.
The third patient had classic, acute onset ME/CFS which
progressed to seizures. Both serum and cerebral spinal fluid tested
positive for HHV6. At the end of the Cifodovir trial the viral load in his
cerebral spinal fluid dropped from 3670 copies/ml to undetectable levels.
Serum HHV6 was dramatically reduced (47,000 copies/ml to 3,000 copies/ml).
Still symptomatic and experiencing cognitive problems, he was nonetheless
able to return to work.
The retrospective study indicated Vistide (cifodovir)
can have dramatic effects on functional capacity in HHV6 and/or HCMV
infected ME/CFS patients.
Increasing VO2 max appeared to be critical to increasing
functionality as the partial responders did not increase their VO2 max
while on Cifodovir. At the FDA Advisory Meeting for Ampligen Dr. Bateman
noted that VO2 max test results probably were, given the exertional
problems in ME/CFS, the most difficult to ‘move’ test result in this
VO2 max levels in Dr. Peterson’s patients prior to
Vistide administration were exceedingly low; they appeared to in the ‘very
low’ range even for people for 65 years of age and older. Vistide moved
those test results about 20% on average; leaving them still, it appeared,
below normal but sufficient enough for a significant increase in
A Vistide Example
The VO2 max tests suggested most patients had not
returned to full health and Dr. Peterson has said he knows of few complete
recoveries. I interviewed a former patient of Dr. Peterson’s several years
ago. Faced with the loss of his career and the ability to care financially
for his family, Vistide turned out to be a godsend.
Cut down by acute onset ME/CFS, his VO2 max score topped
out at an unbelievably low 15 (which qualified him for heart disease) and
he was a ’2′ out of 10 on his own energy scale (had trouble sitting up to
eat). Within a month on Vistide he was at a ’4′; the next month he was a
’5′ and sleeping soundly for the first time since he’d gotten sick. The
next month he was a ’7′ and his VO2 max tests had doubled to 28; still far
below the 44 expected at his age, but an amazing increase, nevertheless.
Three months later he was at ’90%’, back at work and able to do everything
CMX001 – The Future Vistide?
Dr. Peterson didn’t report on CMX001 in Paris, but
sitting in the background of all this is a analogue of Vistide called
CMX001 which appears to be a safer and more effective, if not yet
available, version of it. A 2012 review named CMX001 as one the ‘ten hot
topics’ in antiviral research.
Chimerix Pharmaceuticals modified Vistide so that it can
easily be taken up into the tissues. That means no need for
infusions, no worries about kidney problem and according to Chimerix,
dramatically increased effectiveness.
CMX001 has been in development for some time but
just this March the FDA awarded the drug ‘fast track’ status for the
prevention of cytomegalovirus infection. Phase II trials are finished
and Phase III trials will get underway this year.
Given Dr. Peterson’s success with Vistide, FDA approval
of CMX001 could be very good news for ME/CFS patients with HHV6, HCMV
and/or possibly EBV infections.
In a retrospective study Vistide proved to be effective
in treating severely ill ME/CFS patients with HHV6 and HCMV infections. Dr.
Peterson called for double-blinded, placebo-controlled studies to further
study Vistide’s efficacy and mechanism of effect. The CFI’s pathogen
discovery studies due out this year should shed light on what percentage of
ME/CFS patients could benefit from Vistide.
A Vistide analogue under development called CMX001 which
does not require infusions and does not effect the kidneys could be boon
for ME/CFS patients with herpesvirus infections if it is approved by the
FDA. CMX001 was given fast-track status by the FDA earlier this year.