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Office of Evaluation, Government Performance and Results Act - ^ | 2000 - 2001 (various release dates for studies) | Martinez, Bray, Huggins, ETAL

Posted on 10/19/2001 12:43:31 AM PDT by dandelion

New Drug to Aid in Protection Against Bioterrorism.

Although smallpox was eradicated in the 1970's, smallpox has re-emerged as a public health concern because of its potential use as a biowarfare agent. At present, no drugs exist to treat orthopoxviruses, the family of respiratory-transmitted viruses of which smallpox is a member. Recently, NIH-supported investigators tested the efficacy of a drug called cidofovir against these viruses. Cidofovir is currently licensed to treat an unrelated disease. The investigators, expanding upon prior findings by another research team, found that cidofovir inhibits a broad spectrum of orthopoxviruses in vitro, completely protects monkeypox-infected monkeys from signs of disease, and is highly effective in protecting and treating cowpox virus in mice. These findings suggest cidofovir may be effective treatment for smallpox infection.

Martinez MJ, Bray MP,Huggins JW: A mouse model of aerosol-transmitted orthopoxviral disease. Archives of Pathological Laboratory Medicine, 124(3):362-77. 2000.
Smee DF, Bailey KW, Wong M-H, Sidwell RW: Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir. Antiviral Chemical Chemotherapy, 11(4):303-9. 2000.

Text available HERE (cached text from Google)

Antiviral Drugs
Two hundred seventy-four antiviral drug compounds were screened for activity and therapeutic indices against variola, monkeypox, cowpox, camelpox, and vaccinia viruses by two cell culture assays. Many of these compounds were provided for testing under collaborative arrangements facilitated by an orthopox antiviral research initiative of the National Institute of Allergy and Infectious Diseases. Previous studies identified a nucleoside phosphonate DNA polymerase inhibitor, cidofovir (Vistide), as being active against poxviruses, including variola. In the current trial, cidofovir and its prodrug (cyclic HPMPC) were evaluated against 31 strains of variola, which were selected to cover a wide geographic area and time span. No substantial differences in inhibition among strains were observed, which suggests that cidofovir-resistant strains are unlikely. The in vitro inhibition was further characterized in multiple cell lines to meet FDA requirements. However, another class of antiviral drugs, the S-adenosylhomocysteine hydrolase inhibitors, showed considerable variation in the 50% inhibitory dose between variola isolates; this effect should be investigated further.

Two approaches to the development of an oral prodrug of cidofovir yielded compounds with improved antiviral activity. In addition, the current series of experiments identified 27 other compounds, including completely new classes of drugs, that appear to be active against variola and other orthopoxviruses. In fact, 10 compounds had therapeutic indices greater than 200, while cidofovir had indices greater than 10; 3 compounds had therapeutic indices greater than 1,500. When work resumes in early 2001 with live variola virus, we will continue to evaluate these and additional compounds for activity, including analogs designed for oral administration. The most promising compounds emerging from this in vitro testing will be evaluated in animal models, e.g., cowpox and vaccinia in mice and eventually monkeypox virus challenge in nonhuman primates. All promising compounds will be tested against a battery of surrogate orthopox viruses to guide evaluation of new antiviral compounds after variola virus is no longer available.

THIS FROM NYC DEPT OF HEALTH: Medical Treatment and Response to Suspected Smallpox: Information for Health Care Providers During Biologic Emergencies
Treatment: Supportive care is the mainstay of therapy In-vitro antiviral activity against poxviruses has been shown with adefovir, cidofovir, dipivoxil, and ribavirin. (Animal studies suggest that cidofovir may be most effective.)
VII.Treatment Supportive care is the mainstay of therapy. Currently, there are no anti-viral drugs of proven efficacy. Although, adefovir, dipivoxil, cidofovir and ribavirin have significant in vitro antiviral activity against poxviruses, their efficacy as therapeutic agents for smallpox is currently uncertain. Cidofovir is FDA-licensed and shows the most promise in animal models.

Cidofovir (trade name Vistide, formerly known as HPMPC) is a treatment for CMV retinitis. CMV is a common infection caused by a herpesvirus called cytomegalovirus. About half of the US population are infected with CMV, but the immune system normally prevents the virus from causing illness. In people with immune system problems such as AIDS, CMV can become active and cause illness. The greatest risk for CMV-related illnesses is for people with T-cell counts of less than 50...
Gilead Sciences, the company that makes cidofovir, has set up a patient assistance program for people having difficulty accessing the drug. Call (800) 445-3235 for more information...

TOPICS: Front Page News; News/Current Events
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This is the only credible reference I have seen in regards to a possible treatment for smallpox. Cidofovir has some undesireable side effects, most notably kidney damage; but considering the horrors of smallpox, I would certainly take the risk were I infected.

Bottom line: Cidofovir is available, and appears to be an effective (if not absolute) treatment for smallpox. BUT ACCORDING TO THE NYC DEPT OF HEALTH website it will NOT BE OFFERED due to the fact it is in vitro - experimental. If threatened by smallpox, we should be offered the option to access it for treatment. We need to start asking questions NOW if we want to be able to access this possibly life-saving treatment...

1 posted on 10/19/2001 12:43:31 AM PDT by dandelion
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To: JohnHuang2; 68-69TonkinGulfYatchClub
Well, well, well - pretty please, would you lovely fellas give this a bump in the night? I think it might be bump worthy, especially considering that we are being told there is no treatment for smallpox...
2 posted on 10/19/2001 12:46:51 AM PDT by dandelion
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To: dandelion
yes there is. smallpox vaccine works even after you get infected
3 posted on 10/19/2001 12:51:44 AM PDT by arielb
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To: dandelion
We shouldn't be concerned about TREATING it when we can PREVENT it altogether with vaccination. Since no one has it, vaccination is the issue. And we have the ability to prepare vaccines and get those started... first with people who have never been vaccinated and with the very old, as they will be the most vulnerable.
4 posted on 10/19/2001 12:54:44 AM PDT by piasa
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To: arielb
Considering that there are limited amounts of vaccine available (between 2 million and 15 million, depending on to whom you listen) and considering the fact that the vaccine is old and may have to be diluted to stretch it, I would certainly prefer that I have access to the drugs as well...
5 posted on 10/19/2001 12:54:54 AM PDT by dandelion
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To: piasa
The vaccines that you and I received had a shelf-life of 10-12 years according to medical experts - and once again, thanks to clinton, we have NO plant currently producing vaccine. The planned DILUTIONS of the 15 million vaccines available will not be ready until NEXT SUMMER. If a massive outbreak of smallpox occurs, many may be exposed who will have no access to vaccines. We will need to have the option of accessing this available drug which is currently in production.
6 posted on 10/19/2001 1:02:09 AM PDT by dandelion
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Comment #7 Removed by Moderator

Comment #8 Removed by Moderator

To: dandelion
Interesting medication but it needs a lot more testing.
9 posted on 10/19/2001 1:31:13 AM PDT by Movemout
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To: piasa; JohnHuang2
NOTE: Common name of Cidofovir - "Vistide". A search of the term on this Formulary page reveals another clue as to why the government may not be offering this drug up front - it is expensive. Gilead Sciences offers programs to make the drug available to HIV patients... what, I wonder, are the chances they would make it more available to victims of a massive outbreak of smallpox??
10 posted on 10/19/2001 1:34:04 AM PDT by dandelion
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To: Movemout
If my children have smallpox, I think that they are worthy of the same consideration as an AIDS patient...
11 posted on 10/19/2001 1:35:02 AM PDT by dandelion
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To: dandelion
12 posted on 10/19/2001 1:56:36 AM PDT by gueroloco
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To: dandelion
13 posted on 10/19/2001 1:59:49 AM PDT by Centurion2000
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To: trax2001
The virus can mutate all it wants but it is still susceptible to the cowpox vaccine.
14 posted on 10/19/2001 2:07:42 AM PDT by piasa
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To: piasa
That is, IF you can get the vaccine... this drug is available, and they are saying it appears to be effective against smallpox. The vaccine will not be available until AFTER SUMMER 2003 - and unless you are one of the luck 15-40 million who are chosen to receive it, you will NOT get a vaccine. Cidofovir is already available, it's already FDA approved, and it's already been proclaimed by the government as probably effective against smallpox. It's dangerous, but so is the smallpox vaccine. Cidofovir's available, the vaccine is not. The government has already approved it and tested it - in event of smallpox infection, we should be able to have the option to use cidofovir if we choose.
15 posted on 10/19/2001 2:15:43 AM PDT by dandelion
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To: dandelion
I have used a fair amount of cidofovir to treat CMV.

It is very difficult to use-it is IV (intravenous) only, and causes major side effects, including kidney failure severe enough to require discontinuation, in over 50% of those treated.

The IV infusion itself is difficult and prolonged.

I am interested in the reference to ribavirin, which is used to treat Hepatitis C and is now available in large quaantities both here and overseas.

16 posted on 10/19/2001 2:28:06 AM PDT by Jim Noble
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To: Movemout
Emedicine has a listing of test results and dosages, (use control+find for the word "vistide", the brand name for cidofovir)...
17 posted on 10/19/2001 2:29:44 AM PDT by dandelion
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To: dandelion
Hey, cidofovir looks promising for sure. However, it may not work. The FDA has approved its use for the treatment of CMV retinitis, NOT SMALLPOX. So the FDA believes it is relatively safe, under certain clinical conditions, and relatively effective, under certain clinical conditions, for the treatment of CMV retinitis. It will be VERY VERY DIFFICULT to work out if it's effective against smallpox, because (thankfully) no-one has the disease -- so there's no population on which to test it. Animal models are suggestive but far from conclusive -- plenty of drugs don't get through phase III trials (the big efficacy trials that do double-blinded tests on a big population). So a hint of caution may be in order.
18 posted on 10/19/2001 2:30:00 AM PDT by slhill
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To: slhill
Definitely caution - this would NOT be something one would want to do as a "precautionary measure". However, according to the Emedicine link " Cidofovir (Vistide)- A nucleoside analog DNA polymerase inhibitor; if administered within 48 h of exposure, may attenuate or avoid infection; adefovir, cidofovir, and ribavirin are under investigation for smallpox".

Since we have nothing better, and those who have been studying it have come up with suggested doses, it begs the question - will we be given the option to try cidofovir, considering that it's risks are - by all accounts - significantly lower than that of smallpox?

19 posted on 10/19/2001 2:38:36 AM PDT by dandelion
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To: Jim Noble
Does that rate of kidney failure reflect those patients taking Probenecid? I understand that the rate of kidney failure is quite high in those patients who are not taking Probenecid, I'm curious to the renal failure rate of those who take Cidofovir with Probenecid. Probably no one would prescribe it WITHOUT Probenecid, but I'm not sure if their are contraindications for HIV patients to take Probenecid...
20 posted on 10/19/2001 2:52:02 AM PDT by dandelion
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