full text request: Long-Term Valacyclovir Reduces Number of EBV B-cells

[cfs since 1998]

full text posted: Long-Term Valacyclovir Reduces Number of EBV B-cells

If anyone has access to full text can you please post it in the library. Thank you kindly.

http://www.ncbi.nlm.nih.gov/pubmed/19740997

Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers.

Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, Follmann D, Cohen JI.

Abstract:
Epstein-Barr virus (EBV) establishes a latent infection in B cells in the blood, and the latent EBV load in healthy individuals is generally stable over time, maintaining a "set point." It is unknown if the EBV load changes after long-term antiviral therapy in healthy individuals. We treated volunteers with either valacyclovir (valaciclovir) or no antiviral therapy for 1 year and measured the amount of EBV DNA in B cells every 3 months with a novel, highly sensitive assay. The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P = 0.86). The difference in the slopes of the lines for the number of EBV-infected B cells over time for the valacyclovir group versus the control group approached significance (P = 0.054). In contrast, the number of EBV DNA copies per B cell remained unchanged in both groups (P = 0.62 and P = 0.92 for the control and valacyclovir groups, respectively). Valacyclovir reduces the frequency of EBV-infected B cells when administered over a long period and, in theory, might allow eradication of EBV from the body if reinfection does not occur.

Edit: Full text is now posted. Thanks!

 

[cfs since 1998]

The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P = 0.86)

So I guess they're saying that whatever number of EBV-infected cells you start with, in 31 years you will still have half as many, but if you take valacylovir, you will reduce them by 50 percent in only 11 months. It would take two years of valacyclovir to reduce them to a quarter, etc. I'd like to know what dosage they used.

 

[_Kim_]

Hoshino 2009 - Long-Term Administration of Valacyclovir Reduces the Number of EBV

full text in the Library.

 

[garcia]

Wow Kim, you rock! Very interesting paper.

 

[Gerwyn]

Now this is the sort of study that does drive me nuts p=0.054 is not statistically significant.Ergo it is in scientific terms a chance observation.The novel highly sensitive assay could mean anything.What happened to the total number o B cells in each volunteer.Were they matched groups for viral load in the first place ? The list goes on perhaps the full test will clarify matters apart from the non statisticaly significant results

 

[CBS]

One additional cautionary note concerning valacyclovir (Valtrex). Valtrex is converted into acyclovir (the therapeutically active agent against EBV and HSV-1 & 2) in the liver. Valtrex has been associated with abnormal liver values in HIV patients. There are some docs ID docs that won't prescribe Valtrex for long-term use in possibly immuno-compromised patients, instead preferring acyclovir. Acyclovir does not need to be processed by the liver and is no less effective in fighting HSV-1 but there are national (US) shortages in many dosages.

 

[Hope123]

Interesting article. Not sure yet what to make of it. Just a scan but these questions came up in my head:

- small numbers (50+ people total)
- group taking acyclovir had recurrent genital herpes but were otherwise healthy - I don't know if what works for a healthy immune system would work for us

Discussion part of interest:

"Based on the half-life of
EBV in patients treated with valacyclovir and assuming that
valacyclovir acts similarly on B cells in tissues as it does in the
blood, we estimate that it would take 6 years of 500 mg of
valacyclovir once each day to eradicate 99% of EBV from the
B-cell compartment and 11.3 years to eliminate the virus completely
from the body if persons were not reinfected during this
time. Reinfection with the virus is likely, however, since multiple
strains of EBV are detected in many individuals, suggesting
that multiple episodes of infection occur."

 

[cfs since 1998]

full text in the Library.

Thanks so much Kim!

The article sheds light on the dynamics of EBV infection and treatment. They used a dosage of 500mg per day, which is almost nothing.

Now this is the sort of study that does drive me nuts p=0.054 is not statistically significant.

It's borderline. There are two p-values, one for the number of B-cells before and after (0.02) and one for the rate of decrease (0.054). I speculate the rate of decrease was not as significant since valacyclovir can't actually kill infected cells. I do not agree that p-values are cut and dry; had there been just a couple more subjects or had the study been just a little longer, it probably would have been significant.

Valtrex has been associated with abnormal liver values in HIV patients.

Thanks for the info. Dr. Lerner says doses as high as 4g/day are safe in CFS patients but he does indeed monitor bloodwork every month or so just in case. Of course, HIV patients are probably on HAART so maybe it's HAART+Valtrex combined that causes the liver issues.

I don't know if what works for a healthy immune system would work for us

"Based on the half-life of EBV in patients treated with valacyclovir and assuming that valacyclovir acts similarly on B cells in tissues as it does in the blood, we estimate that it would take 6 years of 500 mg of valacyclovir once each day to eradicate 99% of EBV from the B-cell compartment and 11.3 years to eliminate the virus completely
from the body if persons were not reinfected during this time. Reinfection with the virus is likely, however, since multiple strains of EBV are detected in many individuals, suggesting
that multiple episodes of infection occur."

Good point that these people had healthy immune systems. As we know ours aren't all that healthy. The part you quoted is certainly interesting.

They don't mention drug resistance (especially at such a low dose) as a possible reason why this might not eliminate the virus. I wonder if it is because they think drug resistance is not common or they just forgot about it.

The fact that some CFS patients improve on valacylovir, but that it takes many years tells and is still not a cure, tells me our broken immune systems play an important role in our diseases, even "post-EBV" type CFS. This study and Lerner's studies on EBV CFS taken together seem to be congruent with the XMRV hypothesis.