"HSV in the bloodstream - an ignorant (but technical) question"
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M'sMom Click to check IP address of the poster Dec-12-99, 10:55 PM (CST)
"HSV in the bloodstream - an ignorant (but technical) question"
This looks like it might be the place for this, so here goes:

The reading that I have done suggests that the HSV *virus* may actually show up in the blood for a short period of time during initial infection and then (possibly) around or during outbreaks. (This being the rationale for asking HVS folk not to donate blood during an outbreak.)

Is this known to be true? Or is this "belt and suspenders" logic?

If it's true, how is the presence of the virus (as opposed to antibodies for the virus as WB, Elisa, et al check for) detected?

Also, what is the sequence of events that occurs during primary infection? It seems obvious that the skin is infected first, but I understand that symptoms don't necessarily occur immediately.

What is the temporal relationship between infection of the skin, viral presence in the blood, neural infection and outbreaks?

I would appreciate someone taking the time to answer this, but please type slowly and use small words - I am an engineer, not a medical professional.

Thanks
M'sMom

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 Table of contents

hmmm, Keyser Soze, Dec-12-99, (1)
Round 2, M'sMom, Dec-13-99, (3)
blood, Ocean, Dec-12-99, (2)
M's Mom - i wouldn't worry..., ruby, Dec-13-99, (4)
mad cows, Ocean, Dec-13-99, (5)
What, me worry? , M'sMom aka the elephant's child, Dec-13-99, (6)
Hi Ms Mom, J, Dec-13-99, (7)
hey M's mon :), ruby, Dec-14-99, (8)
Treatment window - is we mice or is we men?, M'sMom, Dec-14-99, (9)
skin tests and mice, windy, Dec-14-99, (10)
Sure, Ocean, but I already admitted I was full of ..., M'sMom, Dec-15-99, (12)
The above is in response to Ocean's request..., M'sMom, Dec-15-99, (13)
Mom, Ocean, Dec-15-99, (14)
~~~, M'sMom, Dec-15-99, (16)
oops., Obviously Ocean, Dec-15-99, (17)
I can't post, I can't read..., M'sMom, Dec-15-99, (18)
~~~, Ocean, Dec-15-99, (23)
Thanks and a human perspective, M'sMom, Dec-15-99, (25)
M'sMom, Ocean, Dec-14-99, (11)
hmm, J, Dec-15-99, (15)
not sure if you're teaching now and, ruby, Dec-15-99, (19)
Drugs, J, Dec-15-99, (20)
doh!, Ocean, Dec-15-99, (22)
O - your post doesn't apply to J's , ruby, Dec-17-99, (42)
Your powers of observation, Sal, Dec-17-99, (44)
i don't see...., ruby, Dec-17-99, (45)
hsv, J, Dec-17-99, (47)
i would caution you..., ruby, Dec-17-99, (49)
drugs, windy, Dec-15-99, (24)
topical, Keyser Soze, Dec-15-99, (26)
Clarification, M'sMom, Dec-16-99, (27)
timing, windy, Dec-16-99, (28)
Topicals & Time windows, Sal, Dec-16-99, (29)
I think I see. . ., Sal, Dec-16-99, (30)
Sal, I had it wrong...., M'sMom, Dec-16-99, (37)
Oh no - no problem !, Sal, Dec-17-99, (38)
my turn to oopsie , Sal, Dec-17-99, (39)
topical, J, Dec-17-99, (48)
from the U of W site, ruby, Dec-17-99, (50)
from the U of W site, ruby, Dec-17-99, (51)
Explanation, please - Have I done something wrong?, M'sMom, Dec-16-99, (33)
~~~, Ocean, Dec-16-99, (34)
we disagree with each other..., ruby, Dec-17-99, (43)
A lot of ..., M'sMom, Dec-17-99, (52)
No, Mom, Keyser Soze, Dec-16-99, (35)
Mom, don't worry, Rajah, Dec-16-99, (36)
Posting for tinman...M's Mom i'm not a doctor, S. Crow, Dec-17-99, (46)

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Keyser Soze Click to Email Keyser SozeClick to view user profileClick to check IP address of the poster Dec-12-99, 10:58 PM (CST)
1. "hmmm"
Mom,
Could you post a reference to where you read this? I would think it is counterintuitive, but I'm a geologist, not a doctor. The only time I've had problems donating blood since I was diagnosed is when I was on suppressive therapy because of the medication in the bloodstream.

KS

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M'sMom Click to check IP address of the poster Dec-13-99, 02:55 AM (CST)
3. "Round 2"
O.K., so I tried this before, but the reply didn't seem to show up. This short answer is: I don't have a good source - just several offhand references and allusions, made by people that I don't think are medical professionals.

So: this whole thought train could easily be bogus, my initial premise is suspect. Thus, the question.

Someone put me out of my misery, please?

M'sMom

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Ocean Click to check IP address of the poster Dec-12-99, 11:26 PM (CST)
2. "blood"
Hi M'sMom,

The reading that I have done suggests that the HSV *virus* may actually show up in the blood for a short period of time during initial infection and then (possibly) around or during outbreaks.

~~~ I too would definetely like to hear more on this. I know hsv finds its way to some strange places sometimes...heart nerves, brain,... but I dont think it would survive long in the blood.

(This being the rationale for asking HVS folk not to donate blood during an outbreak.)

~~~ Im under the impression that the reason not to donate while having an OB is the giving blood can wear you down...which you dont want during an outbreak. Its for the protection of the hsv person.


If it's true, how is the presence of the virus (as opposed to antibodies for the virus as WB, Elisa, et al check for) detected?

~~~Would have to be culture or PCR looking for viral dna. (or some test which presents antibody, to see if virus attaches).

Also, what is the sequence of events that occurs during primary infection? It seems obvious that the skin is infected first, but I understand that symptoms don't necessarily occur immediately.

~~~After the skin, the virus heads for the nerves, where it is "at home". Here it sets up shop. Once in the nerves, it goes latent...basically its DNA just hangs around in the nerve cell until something activates it. It may activate within 2 days, never, or anything in between. (but ussually 2 to 20 days.) Most people dont notice their true primary.

What is the temporal relationship between infection of the skin, viral presence in the blood, neural infection and outbreaks?

~~~ If virus gets in blood, its probably by mistake...like it took a wrong turn or it was swept away or something. In the blood, your immune system would probably kill it quickly as it would not be recognised as "self"

I would appreciate someone taking the time to answer this, but please type slowly and use small words - I am an engineer, not a medical professional.

~~~Me either; maybe J or Rattus can add/subtract.

....Ocean

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ruby Click to check IP address of the poster Dec-13-99, 10:07 AM (CST)
4. "M's Mom - i wouldn't worry..."
LAST EDITED ON Dec-13-99 AT 01:32 PM (EST)

about the blood - the only article that mention H virus and blood are those that discuss the initial onset of herpes - and those are not definative.

you could contact the red cross and see if they have any concerns (i have donated blood many times since contracting H - it's not a virus carried in the blood like hepatitis and AIDS) - the lengthy questionaire that you fill out for the red cross covers all types of scenarios - from sex for money to overnight stays in jail - but i've never heard herpes voiced as a concern. http://www.racoon.com/dcforum/Images/happy.gif";>

i have heard that a rumor that the red cross may exclude people who have traveled to England in recent years due to mad cow disease! go figure!

just remember that many people have HSV-1 - the dna structure between the 2 herpes is 50% the same and actually HSV1 posts more risks to people compromised and in the hospital

- also CMV virus (cytomegalovirus) would be another culprit that people would have to worry about and this is not tested for in blood products at donation.

your question about temporal relationships is excellent - if you ever get the answer to that one let us know

it may have to do with patient viral load and the status of the patient's immune status - type of hsv and other physical stressors - it may be a very individual thing.

good luck and great posts! <img src="

you may want to contact the university of washington with your temporal question - the address to their site is tot eh left under research.


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Ocean Click to Email OceanClick to check IP address of the poster Dec-13-99, 07:42 PM (CST)
5. "mad cows"
Actually Mad Cow disease is somewhat related to Cretzfield-Jacob(?) disease. It is not well understood, but it seems a prion turns your brain to mush after 20 - 30 years from exposure. It didnt make the news for nothing.

...Ocean

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M'sMom aka the elephant's child Click to check IP address of the poster Dec-13-99, 08:06 PM (CST)
6. "What, me worry? "
Hey, Ruby,

Thanks so much for the info. It's not a matter of worry - there are *much* better ways to get HSV than via blood transfusion, and considering my sordid past, if I don't have it yet, I may be the eighth wonder of the world.

These questions came from overworking my poor engineering brain on a problem that's way out of my field.

I was thinking what a bitch the HSV lifecycle is - it seems that by the time you present signs of infection, the herp has already taken up residence in your nerves and we are not currently able to root it out.

I am aware of some murine and at least one human study that suggest that early application of Famvir (w/i 48 hrs or so of initial infection) can discourage if not prevent establishment of the virus BUT apparently it does no good to pre-treat (take antivirals prior to exposure).

SO, think I, (creeping farther and farther out on the logical limb) the first trick here might be to find a way to detect infection very early in the lifecycle while there is still time to discourage establishment. I don't see how you could do this by testing the skin - there is just too much area to cover (Oh, wait - facetiousness break - maybe what we need is some soap that's like the mouthwash dentists give kids that glows red on the areas where they have plaque, you know maybe it could foam and turn green if it encounters HSV on the skin? - Sorry, I'm over that now.) Anyway, stipulating that a skin check is tough to do, blood is a lot easier to monitor.

So, (and this limb is getting real thin now) wouldn't it be cool if there was a way to do a quick blood check and see if you had just been exposed? I realize there are a lot of "ifs" here: if the virus does typically manifest in the bloodstream on initial infection; if it does so before it is well established in the neural tissue; if it does so in a way that could be tested with a finger stick at home, and if the indications that Famvir may have a discouraging effect when applied early enough, then this would be a useful tool for polarized couples at least, allowing the HSV neg person to confirm that s/he's been exposed very early and take immediate control actions.

Unless the process were refined a bit, this would probably be limited to anxiety-provoking situations like discovering an outbreak immediately after sex - I should think that knowing you're gonna have to poke your finger with a needle every time you make love would be negative reinforcement

O.K., so now you know what got me started. Probably pure bupkes due to to some well-known medical fact that I am blissfully ignorant of.

Please feel free to straighten me - gently.

M'sMom

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J Click to check IP address of the poster Dec-13-99, 09:13 PM (CST)
7. "Hi Ms Mom"
Here is alittle more info I copied from various lecture notes on HSV-It does mention viraemia

Primary infection occurs through a break in the mucus membranes of the mouth or throat, via the eye or genitals or directly via minor abrasions in the skin. because of the universal distribution of the virus, most individuals are infected by 1-2 years of age; initial infection is usually asymptomatic, although there may be minor local vesicular lesions. Local multiplication ensues, followed by viraemia and systemic infection. There then follows life-long latent infection with periodic reactivation.
During primary infection, the virus enters peripheral sensory nerves and migrates along axons to sensory nerve ganglia in the CNS - allows virus to escape immune response! During latent infection of nerve cells, viral DNA is maintained as an episome (not integrated) with limited expression of specific virus genes required for the maintenance of latency - true latency.
The delicate balance of latency may be upset by various disturbances, physical (injury, U.V, hormones, etc) or psychological (stress, emotional upset - perhaps affecting immune system/hormonal balance).
Reactivation of latent virus leads to recurrent disease - virus travels back down sensory nerves to surface of body and replicates, causing tissue damage:

HSV
During primary infection of the host with HSV, viral nucleocapsids are translocated by retrograde axonal flow to the cranial or spinal sensory ganglia, where the viral genome persists indefinitely.
Productive infection leads to the destruction of some neurons, but most survive. Studies in mice suggest that these infected neurons are protected by antiviral cytokines secreted by CD8 cells. These have been activated by exposure to viral peptides presented on the surrounding microglial cells but cannot lyse neurons since neurons do not express significant amounts of MHC class I or class II glycoproteins. Interferons reduce expression of HSV alpha genes, required for all other gene activation. Surviving neurons harbor 10-100 copies of the viral genome indefinitely in the form of a non integrated circular extended concatamer. No virus is made because none of the RNA is transcribed. However each latently infected cell produces 1000s of unusual overlapping non polyadenylated antisense RNA transcripts known as latency associated transcripts (LATs) The 2kb LAT is partially complementary in sequence to the mRNA for a key regulatory protein (VP16?)
required for transactivation of later HSV genes.
Following reactivation replication is induced in neurons, virus is transported down the axon to the periphery where it multiplies again in epithelial cells. A CD4 Th cell mediated inflammatory response, perhaps supported by CD8 Tc response quickly leads to the elimination of infected epithelial cells, and preexisting antibodies mop up any free virions.
Advantages to virus of being in neurons.
1. Because the express no MHC antigen are not targets for cytolytic T-cells, also safe haven from antibodies and ADCC
2. Since do not divide there is no need for virus to divide
3. Axon of neuron is many centimeters long, provides a direct pathway to the periphery where virus replication can take place in endothelial cells.

Cellular receptor molecules used by a number of different viruses from diverse taxonomic groups have now been identified. This is achieved by binding of a specific virus-attachment protein on the outer surface of the virion to a cellular receptor molecule on the outer surface of the host cell. The interaction of viruses with a cellular receptors is a major event in determining the subsequent events in replication & the outcome of infections. It is this interaction which 'activates' extracellular virus particles & initiates the replication cycle.

The expression (or absence) of receptors on the surface of cells largely determines the TROPISM of most viruses, i.e. the type of cell in which they are able to replicate - important factor in pathogenesis.

Cellular receptors are largely glycoproteins


Amd a nice picture...


You might want to check out the thread called "J-"

J

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ruby Click to check IP address of the poster Dec-14-99, 10:24 AM (CST)
8. "hey M's mon :)"
LAST EDITED ON Dec-14-99 AT 10:36 AM (EST)

first you are a great addition ot the forum - you would like georgia - she just had a baby recently and doesn't post often - you remind me of her http://www.racoon.com/dcforum/Images/happy.gif";>

i'm not too sure about famvir's and valtrex's ability to be "viricidal" before the virus has "infected" the nervous system - also you would need to take the IC50 of the drug into account - the (-) partner would need a steady state of drug in their body to do anything (rattus had a post on this) - (if anything can be done proactively) - you don't establish efficacy and therapeutic dose/blood level by popping drugs and guessing (seems like the (-) would need to be on supressive Rx).

knowing the marketing crew a drug co.s - if this had a chance to do anything therapeutic - SKB and Glaxo would have been all over it - think of the ching gained.

my guess is that the vaccine with altered virus is the only way to prevent - the murine studies i've seen re: viricidal activity have dealt with HSV1 and occular H infections - and experience has shown that animal studies do not translate to human studies - they give us an idea re: toxicity and pK - but the rest can be a crap shoot.....

if the researchers can not state with confidence that suppressive meds = decreased shedding = decreased transmission i think some vital info still missing just a thought......

take care and great posts! - hope your daughter is doing well <img src="

happy holidays!

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M'sMom Click to check IP address of the poster Dec-14-99, 07:33 PM (CST)
9. "Treatment window - is we mice or is we men?"
Hey, Ruby!

I went back and checked the human study ref I had, and it suggests that famvir reduces reactivation in humans when administered within ONE TO SIX MONTHS of initial infection - which is much longer than it takes to get established. I guess that 48 hr figure was from the mouse studies, and is probably just an artifact of the experiment. I mean, they knew exactly when the mice were infected and they (the mice, I mean) don't live all that long and even scientists have better things to do than sit around and wait for viruses (virii?) to multiply, so that "48 hour" period that I thought was meaningful - probably isn't.

Oh, well, at least thinking about this stuff keeps me from chewing up the carpet or scratching the furniture.

HH to you too, Ruby.

M'sMom

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windy Click to Email windyClick to view user profileClick to check IP address of the poster Dec-14-99, 08:26 PM (CST)
10. "skin tests and mice"
Hi Mom,

Just a couple of things for you to chew on -

The distance the virus has to travel from the surface of the skin to either a blood vessel or a nerve is about the same.

The viral load given to those mice is roughly a lethal dose if they don't get the meds. Then they see what percentage of nerves got infected. My read of the article that Rattus posted was that either Valtrex or Famvir will reduce the percentage of latency, but won't prevent it.

Intravaginal Cevamide (an isomer of capsaicin) does prevent latency in guinea pigs. I don't know if Cevamide is as hot as capsaicin, so I wonder if that method might be a little too exciting.

Heard some talk about the detergent in toothpaste a few months ago, but haven't heard anything since then.

A skin test for the H person might be more practical, to test for shedding. If you want to make some money, maybe you can come up with a rapid at-home PCR test.

windy

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M'sMom Click to check IP address of the poster Dec-15-99, 00:44 AM (CST)
12. "Sure, Ocean, but I already admitted I was full of s**t"
Here it is, but it says nothing about only being effective prior to establishment - only about latency.reactivation stats. That was a bad assumption on my part, based on some stuff I read in mouse studies that in retrospect I think means nothing. That's what I get for reading stuff like this without professional supervision.

Gotta say, I appreciate all of your patience with a stoopid engineer. Since I can't weld it or solder it, I should probably leave it alone, but you know how that 'satiable curtiosity is.

Anyway, here it is, and if it supports my ramblings at all it is surely an accident.

Happy Holidays.
MsMom


Observation May Indicate A Possible
Clinical Effect On Latency

PARIS, FRANCE, October 23, 1996 -- A recent review of
patients attending a genitourinary clinic demonstrated that
famciclovir (Famvir, SmithKline Beecham), when used to treat
first episode genital herpes, was more effective than acyclovir
in preventing recurrence of genital herpes outbreaks after the
cessation of treatment for first episode genital herpes. These
results were presented today at the European Congress on
Sexually Transmitted Diseases meeting of the International
Union Against Venereal Diseases and Treponematoses
(IUVDT) in Paris.

The review was based on 87 patients with the herpes simplex
virus who were treated for five days with either famciclovir
250 mg three times daily or acyclovir 200 mg five times daily.
Only one (4.2 percent) of the famciclovir-treated patients
reported a recurrence within one to six months after the first
outbreak compared to 12 (19 percent) of the
acyclovir-treated patients.

These findings support recent pre-clinical animal findings
which demonstrated that treating first episode herpes simplex
infections with famciclovir may also impact latency/reactivation
of the herpes virus. A study presented last month at the 36th
annual meeting of the Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC)
demonstrated that famciclovir was more effective than
valacyclovir (Valtrex, Glaxo Wellcome) in preventing
recurrence of HSV-1 after the cessation of treatment in
immunosuppressed mice. In addition, an earlier study
published in the Journal of Infectious Diseases found that
famciclovir-treated mice showed markedly reduced evidence
of latent virus, as demonstrated by little or no virus
reactivation. This was not seen in valacyclovir-treated mice.
Based on these results, a worldwide clinical trial to further
examine the effects of famciclovir and valacyclovir on latency
in first episode genital herpes
is being initiated.

Famvir was cleared by the U.S. Food and Drug
Administration to treat recurrent genital herpes in
immunocompetent patients in December, 1995 and is also
currently indicated for the treatment of acute herpes zoster
(shingles). In addition to the major latency trial that is being
initiated, famciclovir is being studied for the treatment of a
number of other infections caused by the viruses belonging to
the family of human herpes viruses in both immunocompetent
and immunocompromised individuals. Studies are also in
progress with this agent in the treatment of chronic hepatitis B
virus infection.

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M'sMom Click to check IP address of the poster Dec-15-99, 00:52 AM (CST)
13. "The above is in response to Ocean's request..."
.... and I wouldn't have to label it if I would post in the right place.

Sorry.

M'sMom

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Ocean Click to check IP address of the poster Dec-15-99, 01:11 AM (CST)
14. "Mom"
Thanks M'sMom,

No need to apologize for being stoopid. It hasn't stopped the rest of us!

...Ocean, (eyes shutting down before reading study...)...Nite

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M'sMom Click to check IP address of the poster Dec-15-99, 07:52 AM (CST)
16. "~~~"
This info seems to support the use of Famvir to attenuate recurrence rate and severity. The 3 common anti-virals, effectively "put a cog in the wheel" of viral DNA replication. Much of this replication takes place upon infection by the virus. The theory that a one-time dose of Famvir limiting latency, is based on its effect during a very limited window of opportunity....while it is "setting up shop". Famvir used one to six months after infection will only effect reactivation directly; it will not effect the virus' initial installation process. (The virus may re-install itself upon retreat from activation.)

One thing we are interested in is the possibility of the anti-virals limiting the initial installation process. For this to happen, the drug must be present before, during, or maybe immedietely after infection. The murine studies are very important and give us a lot of hopefull information and direction. You can't do studies like that on human subjects at this point; (its way to preliminary). Thats what animal models are for. Establishing effective dosage and safety in humans is what "R&D" is for, and is a fairly simple matter. Drug companies are currently shelling out millions of $ to see if anti-virals reduce transmission. Perhaps after this is confirmed, they will study possible effects on transmission, of the neg.partner taking the anti-virals. There certainly have been no human clinicals on this yet.

...Ocean

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Obviously Ocean Click to check IP address of the poster Dec-15-99, 08:15 AM (CST)
17. "oops."
sorry for the mis tag M'sMom.
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M'sMom Click to check IP address of the poster Dec-15-99, 08:56 AM (CST)
18. "I can't post, I can't read..."
Are you saying that I was not way off base with the original idea? If so, that was sheer serendipity.

Upon re-reading, yet again, the humam study I posted, I see that it doesn't really say what the time interval was between infection and treatment (I guess that would be kind of hard to pin down - suspecting that these humans weren't infected in the lab.) So, the only thing that *this* study really says is that famvir may be statistically more effective in reducing the number of outbreaks (at least in the short run) than other antivirals, right?

Is the other idea - reducing replication by treating /w antivirals during the "establishment period" potentially valid? I was pretty sure that was what some of the murine studies were trying to establish, but now I have read so much about this that I am thoroughly consfused. I think I'll go analyze an electrical system to clear my head.

Thanks again to all who have indulged me.

M'sMom

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Ocean Click to check IP address of the poster Dec-15-99, 07:26 PM (CST)
23. "~~~"
>Are you saying that I was not way off base with the original idea? If so, that was sheer serendipity.

~~~...Sorry M'sMom, I think I lost the original idea.

~Upon re-reading, yet again, the humam study I posted, I see that it doesn't really say what the time interval was between infection and treatment (I guess that would be kind of hard to pin down - suspecting that these humans weren't infected in the lab.) So, the only thing that *this* study really says is that famvir may be statistically more effective in reducing the number of outbreaks (at least in the short run) than other antivirals, right?

~~~Yes, however, other studies show Valtrex to be just as good. On a more practical point, from the info shared by many, many people here and from support groups, it seems clear that one works better for some people, the other works better for others. Acylovir is the same drug as Valtrex; Valtrex just has an amino acid of Valine attached with an ester link. This allows it to be absorbed easier, and it is retained by the body longer than acylovir. (So you take it 2X a day vs.5)

>Is the other idea - reducing replication by treating /w antivirals during the "establishment period" potentially valid? I was pretty sure that was what some of the murine studies were trying to establish, but now I have read so much about this that I am thoroughly consfused. I think I'll go analyze an electrical system to clear my head.

~~~ Yes it is potentially valid. It would be a small window of opportunity. It hasnt been studied in humans yet. Drug Co's are still trying to prove that an anti-viral's ability to reduce shedding equates to reduced transmission.
Maybe they will get around to that next; then again, maybe they see a "non-patient" taking meds as a long shot????

(avoid electroshock therapy!)

...Ocean

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M'sMom Click to check IP address of the poster Dec-15-99, 09:09 PM (CST)
25. "Thanks and a human perspective"
First off, thanks to everyone who is contributing. I am learning a lot from this discussion, although I keep having to ask M to explain the terminology. (Bet she gets an A on medical vocabulary this six weeks....)

Ocean, you posted (about researchers) that:

Maybe they will get around to that next; then again, maybe they see a
"non-patient" taking meds as a long
shot????

They may very well think so, and from the perspective of a cure or a preventative, they may be right. However, from the perspective of making life better for the infected, I think this deserves consideration.

Something that appears to bother a lot of HSV people is the impact of the virus on a (-) partner. It seems to me that one major problem would be the goldfish in the blender syndrome - they just can't STAND the tension. Nobody wants to infect their lover, and nobody wants to get infected, but if you and your partner are polarized, it could happen at any time, you won't know it until an outbreak, and there isn't a damn thing you can do about it if it happens. I think that some method of changing at least the first or the last of these conditions could contribute not only to a reduced rate of transmission, but also to some folks peace of mind.

Touchy-feely, yes, but isn't that how most of us got here?

M'sMom

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Ocean Click to check IP address of the poster Dec-14-99, 11:36 PM (CST)
11. "M'sMom"
Can you post your ref to the human study? I think you may be mixing apples and oranges. (two different hypothesis being tested). Thanks

...Ocean

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J Click to check IP address of the poster Dec-15-99, 04:51 AM (CST)
15. "hmm"
"you don't establish efficacy and therapeutic dose/blood level by popping drugs and guessing "

No, but Science does.

Any other questions?

J

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ruby Click to check IP address of the poster Dec-15-99, 10:11 AM (CST)
19. "not sure if you're teaching now and"
LAST EDITED ON Dec-15-99 AT 10:52 AM (EST)

taking questions?

pK studies are done in phase II human studies to determine dosage and AUC and half-life of the drug.

popping pills before intercourse or sexual activity wil not provide a steady state of drug or an effective drug level.

this is why you take famvir for 5 days during OBs to create this

- popping antivirals like a morning (before)after pill does nothing.

it's all a part of researching the drug
- if you know more, i'm sure you'll post it.

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J Click to check IP address of the poster Dec-15-99, 03:45 PM (CST)
20. "Drugs"
Therapeutic drug doses range depends on several things. In the case of suppression, the dose of Famvir is doubled rather than halved because it is dependent on viral thymindine kinase which is less readily available when the virus is in latent stage.

Our attempt here has not been to come up with a dose regiment for the HSV -. I have suggested any and all-suppression for the negative, before and
after sex, etc. We can try to figure it out. My point was that drugs can be effective for the HSV-
I discuss ideas, so do others, and we collaborate.

What I know about the virus.
The virus enters through the skin, replicates in these cells until it reaches a nerve cell where it remains latent until "???????????" This time period is unknown-usual range is 2-21 days but can be indefinitely. After the virion infects, replication begins 3 hours after inoculation for up to roughly 8 hours. Notice the last sentence gives us a range, notice that the virus is also replicating during this range, and notice that we have some idea of when an individual might get infected. This gives us some opportunity to intervene. We now know that the initial replication can be influenced within the first 12 hours after infection. We know that interference in this process may reduce latency and future obs.

Question: "What is the therapeutic drug dose for 12 hours while the virus is initially active?"

J

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Ocean Click to check IP address of the poster Dec-15-99, 07:03 PM (CST)
22. "doh!"
When man 1st dreamed about going to the moon, he didnt have the saturn rocket or the LEM. Man landing on the moon is thus an unfounded notion?

How science works....

Based on previous knowledge, someone comes up with a hypothesis. Only after the hypothesis has been formed, are studies designed to prove or disprove it.

We are discussing hypothesis' here. We are talking about possibilities. We are talking about ideas. A hypothesis is not unfounded until experiments prove it wrong. We are therefore not talking about an unfounded hypothesis, nor an unfounded notion. (unless you can provide evidence for your contrary opinion). Because we dont have labs, we cant think and discuss??? Huh?

The dosage studies for a study like this are already available.

...Ocean

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ruby Click to Email rubyClick to check IP address of the poster Dec-17-99, 10:38 AM (CST)
42. "O - your post doesn't apply to J's "
and J i would suggest that you speak with rattus to check out your theory re you final sentence:

"Our attempt here has not been to come up with a dose regiment for the HSV -. I have suggested any and all-suppression for the negative, before and after sex, etc. We can try to figure it out. ***My point was that drugs can be effective for the HSV-"**

there is no research to support that oral antivrials will be effective for H (-) people.

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Sal Click to view user profileClick to check IP address of the poster Dec-17-99, 11:00 AM (CST)
44. "Your powers of observation"
Ocean's post does not refere to J's - Good observation!

It refered to the rudenest that you, ruby, posted - and the admin board has duely removed it.


Sal

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ruby Click to check IP address of the poster Dec-17-99, 11:09 AM (CST)
45. "i don't see...."
how this relates to the current thread.

you had a post removed - fine.

why post that you had it removed?

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J Click to check IP address of the poster Dec-17-99, 05:05 PM (CST)
47. "hsv"
LAST EDITED ON Dec-17-99 AT 05:12 PM (EST)

There will never be any Human studies. It is unethical to expose a human to HSV, treat or not treat, and then slice up their neurons to check for latency. It's not going to happen. We will never have any proof for you Ruby.

With that said, there is evidence in animal models. ***Early administation (after inoculation) of anitivirals reduces latency and reactivation rate in animals.*** Assuming HSV acts relatively the same whether the cell be animal or human, then it seems likely that antivirals will have a similar effect in humans-the drug will interfere in replication. HSV replicates in the epithelial cells in order to reach the nerve cells, having antivirals in your cells after innoculation WILL interfere with this replication-we know this from reactivation studies-taking anitivirals significantly reduce the frequency and severity of obs. We also know that early administration is crucial-the drug needs to be present during the replicating cycle which occurs at the very beginning of an ob or in the case of inoculation, 3-8 hours after exposure. Antiviral drugs reduce the frequency and severity of obs in both animals and humans. Early administration of anitivirals reduces latency and reactivation rate in animals. Perhaps we can extrapolate just a little further.

We don't have evidence that condoms are effective in reducing the likelyhood of transmitting HSV, but, logic tells us it is likely. The less skin that is exposed equates to overall less exposure in general.

We don't have evidence that taking antivirals is effective in reducing the likelyhood of transmitting HSV. We know that they reduce shedding, hence, seems likely the less you shed, the less likely you will transmit.

Again, we have no proof but If I was in a relationship with someone that I did not want to give the virus to, I would use my logic and wait for the evidence later. If none of these methods help, so be it, I'm not any worse off for trying. If I wait for conclusive evidence, I could be worse off-as one of these measures may have prevented transmision. In any case, I have nothing to lose by thinking for myself.

J

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ruby Click to check IP address of the poster Dec-17-99, 05:24 PM (CST)
49. "i would caution you..."
LAST EDITED ON Dec-17-99 AT 05:26 PM (EST)

on giving prescription medication to someone it's not prescribed for.

the person may have an adverse reaction to the drug or there may be problems with co-adminstering antivirals to the H(-)that you are not aware of. there is also the issue of pregnancy - there is a correlation between miscarriages and some antivirals if the antiviral is given near conception.

no harm is not a given in your proposal.

and there are studies that can be done in human models to see if oral antivirals would help H (-) people .

- they haven't been done (unless you've found some - i know i haven't) and may not be done if the FDA and or drug companies and researchers find that such studies aren't safe or worth exploring due to lack of effect. most likely they would be set up in the same fashion the failed chiron vaccine study was.

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windy Click to Email windyClick to view user profileClick to check IP address of the poster Dec-15-99, 07:39 PM (CST)
24. "drugs"
J,

From what you're saying, it sounds like topical application of the drug might be worth considering. I don't know the pharmacokinetics, so I can't be sure which way would give quicker delivery.

windy

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Keyser Soze Click to Email Keyser SozeClick to view user profileClick to check IP address of the poster Dec-15-99, 10:04 PM (CST)
26. "topical"
Just tossing my 2 cents into the debate here: topical zovirax (acyclovir) doesn't work. That has been proven (I think...correct me if I'm wrong, someone). Maybe topical isn't the way to go? Or maybe it is, but another mechanism for delivery is needed? Or maybe the current antivirals we have don't work topically?

Just an idea...or the rocks rattling around in my head again...

KS

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M'sMom Click to check IP address of the poster Dec-16-99, 01:33 AM (CST)
27. "Clarification"
So, windy, are you suggesting topical treatment prior to possible infection so that the virus encounters the anti-v before it has a chance to get to the nerves et al, or are you thinking something else?

Thanks
M'sMom

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windy Click to view user profileClick to check IP address of the poster Dec-16-99, 07:34 AM (CST)
28. "timing"
Mom,

I was thinking more like after the fact. After the shower, but before that first three hours is up, with an allowance for diffusion time. I was also thinking of topical application plus oral ingestion, to hit it from both sides. Really, I was just wondering which would get into the skin cells first.

windy

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Sal Click to view user profileClick to check IP address of the poster Dec-16-99, 09:08 AM (CST)
29. "Topicals & Time windows"
There are topicals that work

Here in Canada I was fortunate to have "Virostat" Edoxudine Cream 3% during my primary. It was a physician's sample and I found it worked Very well, with almost immediate relief, (I had Zorvirax cream to compare it with as well.)

Reports on Edoxudine have been available on the net presenting excellent testing results (interestingly - it works better for women than men!) - but for what ever reason, the company that controls it's rights in the US has yet to release it.

Also

I am interested to know more about this 3 to 8 hour time window you folks are accepting here -

I believe early treatment will always be the best posiblity, - but somebody commented (was it's M'sMom?) - that anti-viral treatment anytime during the first 6 months can improve one's prognosis with the virus. Based on my understanding and experience with my immune system and the observations of others, this makes sense to me.

HOWEVER- I never could understand why the Medical pros won't prescribe an antiviral to a person suffering from shingles if not within the first day or two - Can somebody explain this time window to me?

Love,

Sal

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Sal Click to view user profileClick to check IP address of the poster Dec-16-99, 09:12 AM (CST)
30. "I think I see. . ."
That 3 - to 8 hour window - is where you figure the strike needs to happen to prevent latency!!

ah ha. . . .

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M'sMom Click to check IP address of the poster Dec-16-99, 11:44 PM (CST)
37. "Sal, I had it wrong...."
..... about antivirals improving the prognosis if administered w/i one to six months. That was the time period after the drugs were administered during which the subjects were observed and reported to have fewer outbreaks - at least I think I'm reading it right this time.

The paper is posted in this thread - might oughta read it yourself, I'm not doing a real good job of synopsizing - I seem to be incorrigably f.o.s.

M'sMom

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Sal Click to view user profileClick to check IP address of the poster Dec-17-99, 08:30 AM (CST)
38. "Oh no - no problem !"
- But I see how you had a re-think, and I was just stumbling along anyway! - besides - there's nothing there to say that taking antivirals in the early stages of infection (say 6 months) Isn't a good idea. . . Until we have proof, I'll settle for feminine intuition!

and I recall the "observation report" that you shared with us above - It was "hot news" at the time - and caused lots of the HHP forum members to radically swing to Famvir as the be all and end all - as it turns out Valtrex is probabaly equivalent - and in the end, what ever works best for the individual is . . .

I believe this observation report could be considered a press release from the famvir company - it served them well!

It was the time window conversation that twigged me to run off on a tangent and ask a question that has long been on my mind.

A couple of years ago, several older people in my community, coincidentally, had 'Shingles' (a painful re-activation of the chicken pox virus they were most likely exposed to as children)

This Herpes Virus ( Chicken pox/shingles - I forget the number) is commonly treated with the same anti-viral drugs used for 'our' herpes

- But one of these lady's doctor refused to give her anti-virals saying it was "too late" - that the outbreak must be caught within the first days or anti-viral treatment would be of no use. - She went on to suffer with Shingles for several months - she missed a lot of time at work and so on- by the end of the winter, this beautiful mature woman was considerably weekened. (while the other who got the early anti-viral were fully well in much shorter order)

The whole thing made no sense to me - I would have liked to have seen her at least given the opportunity to TRY the anti-virals. . .

I have wondered ever since why those first few days of a shingles outbreak would be so crucial, when, while we know it's best to catch it early - but for HVS 2 any - anti-virals still improve things even if administered late. . .

That's what I was babbling about

I should probably post a new thread about it some time.

love,

Sal

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Sal Click to view user profileClick to check IP address of the poster Dec-17-99, 08:49 AM (CST)
39. "my turn to oopsie "
Not wanting to fault the Famvir company for our translations!

Seen in context, in 1996, I believe the goal of the studies for the report you cite is - was to see if dosage regimens could be simplified. - Before the advent of Famvir - Acyclovir was taken 5 time a day, and it's effectivness was greatly influenced by the compliance (or forgetfulness) of the patient - A once or twice a day dosage is much easier to maintain.

I figure that's what that report was about.

love,

Sal

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J Click to Email JClick to check IP address of the poster Dec-17-99, 05:19 PM (CST)
48. "topical"
The only thing I'd worry about topical medication is having it in the cells that need it.


J

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ruby Click to check IP address of the poster Dec-17-99, 05:30 PM (CST)
50. "from the U of W site"
3.Is there any treatment for genital herpes?

Acyclovir (Zovirax) is used for the treatment of HSV-2 infections. Recently,
Valacyclovir (Valtrex) and Famciclovir (Famivir) have also been approved. These
medicines can be used for each episode of genital herpes, or daily to prevent
recurrences. During the initial infection, they can decrease the discomfort and
healing time of lesions, as well as prevent the development of new lesions.
Acyclovir ointment is ineffective.

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ruby Click to check IP address of the poster Dec-17-99, 05:41 PM (CST)
51. "from the U of W site"
3.Is there any treatment for genital herpes?

Acyclovir (Zovirax) is used for the treatment of HSV-2 infections. Recently,
Valacyclovir (Valtrex) and Famciclovir (Famivir) have also been approved. These
medicines can be used for each episode of genital herpes, or daily to prevent
recurrences. During the initial infection, they can decrease the discomfort and
healing time of lesions, as well as prevent the development of new lesions.
Acyclovir ointment is ineffective.

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M'sMom Click to check IP address of the poster Dec-16-99, 08:33 PM (CST)
33. "Explanation, please - Have I done something wrong?"
Hi, all.

When I posted this question, I was under the impression that the reason that this forum is titled "Technical" is that we discuss the scientific aspects of herpes here. It was my understanding that this is a public forum, that no creditials are required to post. I am not aware that anyone is going to perform any sort of human experiments based purely on the postings at this page, without benefit of appropriate analysis and supervision by qualified medical personnel.

Please let me know if I am wrong about this. If so, I never should have posted here - I am not a doctor.

Thanks
M'sMom

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Ocean Click to check IP address of the poster Dec-16-99, 08:57 PM (CST)
34. "~~~"
No, Mom, you got it right.
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ruby Click to Email rubyClick to check IP address of the poster Dec-17-99, 10:41 AM (CST)
43. "we disagree with each other..."
LAST EDITED ON Dec-17-99 AT 03:07 PM (EST)

J and i disagree on one sentence in one post.

and that's all it is.

- a disagreement on the content of a post - something that should be able to be addressed in an OPEN forum.

your post added a lot to the forum, M's Mom. look at the responses you've generated!

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M'sMom Click to check IP address of the poster Dec-17-99, 05:59 PM (CST)
52. "A lot of ..."
...waste heat, I think, but it's been very educational for me.

I appreciate all your inputs.

M'sMom

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Keyser Soze Click to Email Keyser SozeClick to view user profileClick to check IP address of the poster Dec-16-99, 09:46 PM (CST)
35. "No, Mom"
Mom,
You didn't do anything wrong. Your idea was and is still perfectly legitimate. I think that a lot of good is going to come out of this discussion--don't be intimidated by the bickering that's going on--it has NOTHING to do with you.

Love,
KS

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Rajah Click to Email RajahClick to view user profileClick to check IP address of the poster Dec-16-99, 09:54 PM (CST)
36. "Mom, don't worry"
Your post is exactly one of the things that this forum is for. There is only one doctor, to my knowlege, that posts here from time to time and that is Rattus. We all have different levels of technical knowlege and this is supposed to be a forum where technical questions can be asked by anyone. So please don't be shy with questions and comments.

I am very glad to have you on this forum, engineer to engineer, parent to parent and as people who are affected by this virus in whatever way.

(((HUG)))

Rajah

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S. Crow Click to check IP address of the poster Dec-17-99, 01:06 PM (CST)
46. "Posting for tinman...M's Mom i'm not a doctor"
but i have played doctor. and thats how i came to be here.

My personal experience with Famvir, if memory serves me correctly, I began a regimen of 200 or 250 mg of Famvir, twice a day for 5 days after visiting the doc. That visit was 4 or 5 days after the big ob(over the weekend and the s.o.b. was too busy to see me on monday). approx. May 30th '98.

The 1st week of December 98 i had my second very mild ob, unfortunately during a period of informed unprotected sex with my then gf. At approx. the same time or shortly after she developed a sore, what i believed to be a lesion. She, being a former obstetrics nurse(supposedly knowledgeable) and stubborn, refused to take the time to visit her doctor for an exam.

At the time of what i believe to have been her infection there were discussions that a dosage of 500mg Famvir 2 times a day for 5 days was benenficial in reducing recurrences of H if not eliminating them altogether. I probably violated all sorts of laws and obtained pills.

To this date a year later neither of us have had another ob, knock on wood. Is it the Famvir to thank or just luck? Not a clue here. It is possible that if we/she hadnt been as observant her symptoms may have been so mild anyway that she would have ended up being in that 2/3 of H'ers that have it but dont really know it.

So whats my point? i dont know....just dont tell my mom or the law.

S. Crow

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