Getting "die-off" symptoms or "herxing" from valtrex or other herpes antivirals, doesn't make sense to me. Because valtrex works by stopping viruses from multiplying, by inhibiting viral DNA polymerase, it doesn't kill them
So there can't be die-off because the viruses live their normal life-span, they just are unable to replicate and multiply, therefore lowering the viral load. This is one reason why I think antivirals work in some other way to help some us, rather than lowering viral loads.
At least this is how I understand how herpes antivirals work.
It is true that the valacyclovir doesn't kill the latent EBV virus, and the same sentiments you express went through my mind as I tried to make sense of my first 3 months on valacyclovir. However, as my symptoms were so reminiscent of a herx, I began to wonder if those who have very actively replicating EBV virus may not display some sort of immune reaction on initiation of a DNA polymerase inhibitor.
My thought is that, if you have viral DNA in a cell in various stages of replication, along with the viral proteins in various stages of completion and assembly, and you use a DNA polymerase inhibitor to halt that process, inclusive of a halt on the viral proteins that inhibit immune activation and B-cell apoptosis, you may get some immune recognition, B-cell apoptosis, and immune-mediated cell destruction. This would result in immune activation from enhanced immune recognition and spillage of viral proteins into the extracellular space, leading to symptoms.
My theory is not provable (I don't think, although I haven't done a deep dive), but it is my working theory based on my experience. Prior to valacyclovir, I had chronic lympnode swelling and sore throat and my PEM events were very flu-like. At first I could only tollerate 1 valacyclovir each day due to fever and exacerbated fatigue symptoms. Over a period of 3 months, I built up to 3 per day, but would still have some medication related fatigue. Now I take it like it is nothing. My doctor said this is a common experience.