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Low Dose vs High Dose Antivirals

Oberon

Senior Member
Messages
214
Hi Everyone,

I was wondering if anyone's done research on the efficacy of lower doses of antivirals versus higher doses for CFS? Are there any studies out there?

I have one doctor recommending a lower dose of Famvir - 500mg, while another doctor is recommending 2000-3000mg Valtrex and I'm having trouble deciding on which approach to take.

I'm always hesitant to take more than is necessary due to potential toxicity issues, but I don't want to take away from the effectiveness of the treatment plan.

Thank you.
 

Timaca

Senior Member
Messages
792
I can share with you my personal experience. I took valcyte for 9 months (if I remember correctly)...and I've also taken antibiotics. I'm currently on Valtrex.

I was taking 500 mg of Valtrex twice a day but since I've been doing better, I asked the doctor if I could cut down to once a day and see what happened.

I ended up with many more HSV1 outbreaks....and it wasn't just a sore on the lip...it was brain fog, disconnected feeling, harder to type, walk, more fatigue, etc. I was really quite shocked how the HSV1 reactivation affected my whole person! So I went back on my twice a day valtrex. Just recently, I had another HSV1 reactivation (on my lip--probably due to my battling a cold) and it was much less severe for me. In fact, I really didn't notice it affecting me except for a small sore (2 actually) on my lip.

I learned a really good lesson....I need two valtrex a day to keep the HSV1 from giving me substantial problems!

I don't know if that helps you at all.......That does seem like a lot of Valtrex....but all I know is what I've done.....

Best,
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,076
Location
australia (brisbane)
250mg twice a day was enough for me for along time. Now i take 500mg twice a day. If i get a viral flare up or shingles i take my 500mg dose anywhere from 3 to 4 times a day. Throw some lysine in and zantac as it can increase t cells to fight shingles.

So for me only the high doses for short period of times. If one was going to use really high doses for awhile id ask my dr about regular blood work to keep an eye on liver and kidney function, although those doses have been safely used. Monthly blood work??
 

ukxmrv

Senior Member
Messages
4,413
Location
London
500mg a day of Valtrex did nothing for me.

It wasn't until I stopped and started again at 1000mg that I noticed immediate and obvious differences. The terrible burning heat in my spine and limbs at night was much better. My sore throats and glands were improved.

Problem is that I need to keep taking it. Can't afford to try a larger dose.
 

Hip

Senior Member
Messages
17,789
I was wondering if anyone's done research on the efficacy of lower doses of antivirals versus higher doses for CFS? Are there any studies out there?

I have one doctor recommending a lower dose of Famvir - 500mg, while another doctor is recommending 2000-3000mg Valtrex and I'm having trouble deciding on which approach to take.

You might want to look at Dr Lerner's studies on Valtrex and Famvir for treating Epstein-Barr virus infections in ME/CFS patients: see this post. Lerner used Valtrex 1,000 mg taken every 6 hours, and when patients had side effects from Valtrex, he used the same dosing of Famvir, which is usually a better tolerated drug.

But Valtrex / Famvir is only used for patients with an active EBV infection; for active HHV-6 or cytomegalovirus infections, he used Valcyte.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,076
Location
australia (brisbane)
500mg a day of Valtrex did nothing for me.

It wasn't until I stopped and started again at 1000mg that I noticed immediate and obvious differences. The terrible burning heat in my spine and limbs at night was much better. My sore throats and glands were improved.

Problem is that I need to keep taking it. Can't afford to try a larger dose.

The cost of antivirals was the big push for me to look for cheaper meds online. It was costing me $200 a month and of on current dose that would be $400 a month. I payed the money the first year and improved substantially but i couldnt keep forking that sort of cash out.

Online pharmacies opened up a new world. Once past the paranoia of buying medicines online it opened up alot more avenues to experiment to try and improve my quality of live. No more going to the dr and begging to try some mundane medication which may help but just get a weird at you over the top of their glasses.

I have compared medicines online with meds here and found no difference or i got a known sife effect of the online drug eg doxycycline you get burnt very easily in the sun. An outside wedding in the australian summer sun, not a good idea to do anything. 20mins it was and then we all moved undercover. People were starring at me, wow you been to the beach or something. I went to the toilet, i was bright red, skin was on fire, there was no doubt i was on doxycycline.

Antivirals id stop occassionally and immune markers would jump up, back on my cheaper online antivirals and these immune markers would settle down. Regular health checks are fine, liver and kidney function etc

People need to do their own research and weight up the risk to benefit.
 

Oberon

Senior Member
Messages
214
Thank you everyone for all of the feedback. It sounds like lower doses may work depending on the person.

I think I may try the lower dose of Famvir for a few months to see if it helps at all and if not I'll jump on to Dr. Lerner's protocol with Valtrex at closer to 2g-3g of Valtrex.
 

used_to_race

Senior Member
Messages
193
Location
Southern California
I was on 3g/day Valtrex for 6 weeks, and I believe this caused an unprecedentedly huge crash for me, lasting several days. This was actually just last week. I have since returned to "baseline sick", and will probably try to get back on 1g/day at some point, because it did keep my EBV titers and occasional cold sores under control.

I obviously did not carry out the full 6 months to 1 year of treatment that Dr. Lerner has specified, but I will say that my EBV PCR became totally negative on Valtrex and I did not notice any appreciable change in my (relatively mild) CFS symptoms.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
I have engaged a lot with the topic of antiviral treatment in the past year, so perhaps I might also contribute some experiences.

I think there is three groups of people

(1) Those who use antivirals to combat particularly nasty or recurring herpes outbreaks, esp. cold sores.

(2) Those who have active herpes virus infections (esp. EBV, CMV), i.e. positive IgM antibodies and/or evidence of viral DNA via PCR over a lonter period of time.

(3) Those who don't have positive IgM antibodies, but may have positive EBV early antibodies and/or high CMV or HHV6 IgG titers and who are using antivirals per Dr Lerners protocol (see @Hip's post).

For group (1), low doses might just work fine. Group (2) can start on a lower dose and see if it works, i.e. if the IgM goes down, and if it doesn't, can up their dose.

The tricky case is group (3). As @Hip pointed out, the idea behind Dr Lerner's protocol is that CFS in some patients is caused by ongoing (incomplete) herpes virus replication that cannot be detected by today's blood tests (except some evidence for EBV early antibodies).

Dr Lerner suggests to use high doses of antivirals over a long term to drastically reduce the herpes virus in the body and those reduce or stop virus replication that is causing the symptoms. For EBV, that means high-dose Valacyclovir (Valtrex), and for CMV and HHV6 it means high-dose Valgancyclovir (Valcyte).

I'll explain the rationale for EBV, which is what I have, but I think it's the same for CMV and HHV6.

The idea behind Dr Lerner's treatment is to stop EBV replication to an extent that does no longer infect new B-cells (the virus reservoir) during episodes of reactivation that periodically occur in any infected person. B-cells - both infected or uninfected - are replaced in about 3 months, so if EBV replication is stopped over many months, the number of infected B-cells is expected to fall and the damage EBV can do to the body is reduced.

For this purpose, a rather high dose of antivirals is required, as Dr Lerner says, it is imperative to reach the IC50 concentration (when 50% of viral replication is stopped) over 85% of the day. Dr Lerner's protocol, therefore, is 4000mg Valtrex a day (1000mg every 6 hours) and even 6000mg for those above 80kg weight.

There is evidence that lower doses could also accomplish that goal, but it may take longer. For instance, a 2009 study demonstrates that even 500mg once daily can reduce the number of infected B-cells substantially:

http://jvi.asm.org/content/83/22/11857.full

The same study concludes that long-term Valacylcovir treatment might even be successful to eradicate EBV from the body (over several years), however, for this purpose, a dose of 3000mg a day (1000mg every 8 hours) would be required for several years.

Dr Lerner also mentions that after 12 months of treatment, many patients can reduce their dose and still retain the benefits.

My personal experience is that I had fantastic benefits with the high-dose protocol of Dr Lerner in the first 6 months. Joint pain totally disappeared (could hardly walk from bed to kitchen before), PEM is almost gone, heat intolerance is much better, fatigue and concentration are somewhat improved.

Valacyclovir is a relatively safe drug and is well tolerated by most people even in high doses and over longer periods of time. However, it can affect the kidney and this has to be monitored. I developed some problems with the kidneys after 6 months. As recommended by Dr Lerner I did regular blood tests every 6 weeks and it showed that kidney function deteriorated. I then had to switch to Brivudin which is a different antiviral that doesn't affect the kidney. My feeling is that it also helps to some extent, but that it is not nearly as effective as Valacyclovir.

I am now starting Valacyclovir again at 5000mg a day instead of 6000mg (5x 1000 instead of 4x 1500) and hope I can tolerate it.
 

Hip

Senior Member
Messages
17,789
Interesting that brivudine has some efficacy against EBV, I did not know that, but the paper you linked to in another post indicates it does.

Regarding valacyclovir/acyclovir kidney issues, I read that these drugs can cause crystal nephropathy in the kidneys, which this paper indicates can be due to acyclovir crystals forming in the kidneys (acyclovir is poorly soluble in water, so I guess easily precipitates out of water).

Perhaps there may be ways to mitigate this, like say just drinking more water.
 

JES

Senior Member
Messages
1,318
Thank you everyone for all of the feedback. It sounds like lower doses may work depending on the person.

I think I may try the lower dose of Famvir for a few months to see if it helps at all and if not I'll jump on to Dr. Lerner's protocol with Valtrex at closer to 2g-3g of Valtrex.

With Lerner's dosage you need to be monitored for kidney function. So much anecdotal evidence suggests it may cause problems in the long run. According to what I read, Lerner was very stringent with checking lab values of all of his patients regularly.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
Interesting that brivudine has some efficacy against EBV, I did not know that, but the paper you linked to in another post indicates it does.

That is correct, although that's just one single case in which they tried it. Another advantage of Brivudine is the long half-life, so you only need to take it once daily. But in the long run, it is potentially liver toxic, and use over one week is discouraged. I took it for 7 weeks in total, without my liver lab tests getting worse, though. I also read that the no-effect dose for the liver for long-term use was just about the therapeutic dose (125mg), so if you stick to it, the likelihood of severe adverse effects should not be too high. I haven't seen a direct comparison, but I'd say it is probably less liver toxic than Rifampicin, which patients get over many months for Tuberculosis.

That said, my feeling is that Brivudine is less effective than Valacyclovir. It seemed to me that it helped retain the benefits of the 6 months Valacyclovir treatment I had prior to switching to Brivudine, but I didn't notice any meaningful additional recovery during the almost 2 months in which I took it.

Regarding valacyclovir/acyclovir kidney issues, I read that these drugs can cause crystal nephropathy in the kidneys, which this paper indicates can be due to acyclovir crystals forming in the kidneys (acyclovir is poorly soluble in water, so I guess easily precipitates out of water).

Perhaps there may be ways to mitigate this, like say just drinking more water.

Thank you for pointing this out, this is of course correct. Dr Lerner says if you drink six 8-ounce glasses of water a day, there should be no problem with renal calculi.

I was aware of this and I am sure I was well above this amount of water every day while I took Valacyclovir. Additionally, my urine was tested for calculi and did not contain any.

Therefore, I think the problem wasn't the calculi, and it was some general nephrotoxicity.

But I'll try even some more water now, perhaps it helps ;)
 

Timaca

Senior Member
Messages
792
Thanks for sharing about the crystal neuropathy. I was not aware that those drugs could cause that. Even though I am on a much lower dose of Valtrex (500 mg twice a day), I will be sure I drink lots of liquids!!
 

Patrick*

Formerly PWCalvin
Messages
245
Location
California
I've had an active EBV infection (IgM very high) for at least the last 10 months. Before that, previous tests were always IgG positive only - albeit very high titers. At first, my doctor started me on 500 mg 2x/day. We tested again and there was almost no change. We went up to 1G 2x/day - I still tested high IgM titers. Just last week I showed my doctor Dr. Lerner's recommendations, but I expressed reservations that I could stick to a schedule of taking it every four hours, day and night. So we settled on 1G 3x/day (one with each meal). It's too early to tell if this is working. I'm using Byron White formulas EB/H6 at the same time.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
It's every six hours and Dr Lerner explicitly says you don't need to wake up at night to take a dose, so you take the last dose when you go to bed and the first immediately when you wake up.

But I suspect 1G 3x/day will also have a good effect.
 

IreneF

Senior Member
Messages
1,552
Location
San Francisco
Dr. Montoya was asking for blood samples at every visit, but he finally concluded that there was no correlation between antibody titers and symptoms.

He does seem to think that Valcyte dampens neural (glial) inflammation. I do better when I'm on Valcyte, but it's a change from completely housebound to slightly less housebound, less brainfog, less severe PEM. I really value it, as I think anyone would, but it's expensive and I have to monitor my kidney and liver function. Luckily I'm pretty healthy in other respects.

I take 450 mg x 2. I'll ask him about upping the dosage, but I don't think I'll be seeing him till early next year.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
@used_to_race Dr Lerner writes in his papers that a worsening of symptoms in the first weeks of treatment is probably a Jarish-Herxheimer reaction and indicates good response. He said this reaction should be over by week 6.

I had it, too, but it lasted for only about 3-4 weeks. It felt a bit strange. I was clearly getting worse during that time, but it felt like it is part of the recovery, like when you have the flu in the final part of it when you still feel quite sick, but it feels like you're on your way to getting better.

I'm not saying you should continue high-dose treatment, I don't know what the right treatment is for you - just sharing my experience.
 

Seven7

Seven
Messages
3,444
Location
USA
The reason why they start low is becuase CFS patients react too strong to meds. But they will treatrate you up eventually ( was my experience) give the the lowest amount possible that will bring down the symptoms / titters.
Also, some antiviral like Famvir has to be given more often than Valtrex for example becuase does not last as long in your system. So you need lower dose more often.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
Also, some antiviral like Famvir has to be given more often than Valtrex for example becuase does not last as long in your system. So you need lower dose more often.

Valtrex half-life is 2.5-3.6 hours, Famciclovir is 2.0-2.3 hours, so yes it is a bit shorter for Famciclovir, but Dr Lerner recommends the same dosing and frequency for both drugs (i.e. 1,000mg four times daily for patients <80kg).

Regarding the dosing, Valtrex bioavailability is lower for higher doses, i.e. if you take 1000mg at once, a smaller fraction is absorbed as if you take 500mg in two doses several hours apart. This effect is not observed with Famciclovir, absorption is almost entirely proportional to the dose.