Anti-Viral Nonsense

There are some “alt-med” treatments for autism that are like the zombies in B-grade horror movies. You think they’re dead, but as soon as you turn your back, they’re up and shambling around, searching for…..well, they’re usually looking for money, so they don’t fit the zombie analogy that well.

Chelation, secretin and HBOT have all been shown to be no more than profit centers for “alternative” practitioners, but my contacts in the “biomed” world tell me that they are still being prescribed (and inflicted) on autistic children. Apparently, it’s going to take more than decapitation or a stake through the heart to put these undead therapies in the ground for good.

Which brings me to the undead therapy that has – I would have thought – the best reason to be dead, buried and resting in peace: acyclovir/valacyclovir.

For the past few years, I had been living in blissful ignorance of the ongoing use of acyclovir and valacyclovir in the “treatment” of autism. Sure, they were “hot stuff” a few years ago, back when some misguided practitioners were using them to treat “chronic measles infection”. But I thought that people had wised up and realised that these anti-viral drugs have absolutely no effect on measles and – in plain fact – can’t have any effect on the measles virus.

Fast forward to a few months ago, when a worn-out mom asked me if I thought that acyclovir would be as effective as valacyclovir for the treatment of chronic measles.

My initial thought was that they would be equally ineffective, but I managed to keep that thought from being voiced. Instead I asked, “Are you sure that your doctor is using valacyclovir for measles?” The answer was chilling – the undead zombie of “valacyclovir for chronic measles” had risen from its restless grave.

 

Before I go any further, it might be useful to explain what acyclovir and valacyclovir are, how they work and what their side-effects are.

How acyclovir and valacyclovir work:

The “parent” drug is acyclovir, which was first licensed for use in the US back in 1982 (it is currently off-patent). Valacyclovir (USFDA approved 1995) is simply acyclovir with valine (an amino acid) bound to it to improve its uptake from the gastrointestinal tract (55% vs 10-20% for acyclovir). The valine is cleaved from valacylovir by esterases in the liver, releasing the active drug, acyclovir. So, when it comes to efficacy and side effects, the two drugs are pretty much identical. When it comes to cost, valacyclovir is more expensive, though there is a generic form.

Acyclovir (and, thus, valacyclovir) works by interacting with the enzyme thymidine kinase. This enzyme takes thymidine deoxynucleoside and phosphorylates it to TMP, which then is further phosphorylated to TTP, which is a component of DNA. Herpes viruses happen to make their own thymidine kinase, which they need because they replicate in non-dividing cells (e.g. neurons) that don’t produce TTP (but do produce ATP, CTP and GTP, needed for RNA synthesis). Herpes viruses also make ribonucleotide reductase, which can convert these ribonucleic acids them all to the deoxy- form needed for DNA.

OK, maybe that was more information than some people wanted. The “short form” is that herpes viruses make their own thymidine kinase because, in “resting” cells (i.e. non-dividing cells), the cellular thymidine kinase is “switched off”.

The reason that acyclovir works against the herpes viruses and doesn’t simultaneously kill all the cells of the patient is that the viral thymidine kinase is not as specific – as “fussy” – about its substrate as the cellular (human) thymidine kinase; it will take the acyclovir molecule and phosphorylate it. The cellular enzyme, however, isn’t perfect, it will also phosphorylate acyclovir, but at only 1% the rate of the viral thymidine kinase.

Once acyclovir is phosphorylated by thymidine kinase, cellular enzymes further phosphorylate it to the triphosphate form and then the viral (or cellular) DNA polymerase can add it to the growing DNA chain (it “looks” like GTP). Once added, however, it lacks the 3′ -OH needed to add the next nucleotide and the DNA chain stops prematurely (premature termination). Needless to say, if the virus cannot replicate its genome, it can’t form new viruses and can’t infect. That’s how acyclovir and valacyclovir work.

Side effects:

Remember that the herpes virus thymidine kinase activates acyclovir 100 times faster than the cellular (human) enzyme. Well, that’s why acyclovir is relatively non-toxic. That, of course, is “relative to other anti-viral agents”, which is rather like saying “safer than swimming with sharks”. Still, acyclovir is pretty safe, apart from the rare renal failure seen during longer treatment.

Considering how dangerous herpes virus infections can be (and how painful), acyclovir and valacyclovir have very favorable risk:benefit ratios… IF they are being used to treat a herpes virus infection (more about that later).

What about measles?

Yes, what about measles? You’ll have noticed that I didn’t mention anything about measles. Or other viruses, for that matter. Well, as it turns out, acyclovir (and its close relative, valacyclovir) don’t have any effect on measles. Even though acyclovir has been used in the treatment of HIV/AIDS, it is primarily to suppress herpes virus. Acyclovir isn’t even effective against all herpes viruses – CMV and EBV aren’t that susceptible.

So, why isn’t acyclovir effective against measles? You’ll recall that I discussed how acyclovir interferes with DNA synthesis, blocking the replication of the herpes virus genome. Measles virus (wild type and vaccine strain) has an RNA genome. That’s right, it doesn’t make DNA. Not even a bit. So a drug that interferes with DNA synthesis is pretty much useless against measles.

Let me repeat that: measles is an RNA virus without a DNA stage, so drugs like acyclovir and valacyclovir – which interfere with DNA synthesis – have no effect on measles.

However, the side-effects from acyclovir and valacyclovir are present whether or not the drug is given for a rational reason.

“But it works!”:

Inevitably, someone will reply “But valacyclovir helped my child recover from autism!” It may be true that their child’s improvement happened after the valacyclovir was started, there is no plausible physiological reason that the improvement can be tied to the drug. Coincidences happen, and for every person I’ve heard say that valacyclovir “recovered” their autistic child (1), I’ve heard twenty or more say that it had no effect.

Summary:

Acyclovir and valacyclovir are relatively safe anti-viral drugs that are effective against herpes simplex virus (types 1 and 2) and, to a lesser extent, varicella/herpes zoster/chicken pox. They are also somewhat effective against the herpes viruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV).

Acyclovir and valacyclovir are not effective against measles virus (or mumps or rubella or polio or….) or any other RNA virus. In fact, they aren’t effective against anything other than the herpes viruses.

If your child’s doctor has prescribed or recommended acyclovir or valacyclovir to treat “chronic measles infection” or autism or, for that matter, anything other than a herpes virus infection, you should seek an independent second opinion.

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