@zzz, I know it may be difficult to put numbers on such a subjective thing, but where would you say you were healthwise, relative to "normal" health being "100%," before you started doing the very low dose Valcyte (7-14 mg), and to what percent level did you improve to afterwards/now?
This is especially difficult with Valcyte, as it has multidimensional effects, and I think that simply averaging all the effects in all the different dimensions would not give a helpful picture of what's happening. Nevertheless, I recognize the importance of having some objective assessment of what I've been experiencing, so I will do my best.
In the summer of last year, I started on the Goldstein protocol, and I was about a 2 on PR activity scale. (I shall use this scale, as it's what I'm used to thinking about.) By the end of the year, I had increased to about a 5. I had hope to increase more than that, but two main obstacles stood in my way. My sensitivity to medications was extremely great, and I especially could not tolerate virtually any ototoxic medications, as they made my tinnitus significantly worse to the point where it was very difficult to deal with. Unfortunately, the vast majority of medicines are ototoxic to some degree or another, and this greatly restricted which of Dr. Goldstein's medications I could use. Many of the ones I tried had great effects, but the severe tinnitus they generated for me (which was quite unusual - mot people don't have this type of reaction) made them impossible to use. Nevertheless, the ones I was able to use were very helpful, and enabled me to make that jump form an activity level of 2 to 5.
Unfortunately, at the end of last year, a gut problem that I'd had for eight years started getting much worse, and all the treatments I had been using to contain it were no longer sufficient. As a result, my health plummeted, and within a few months I was back at a 2, being almost bed bound.
In February of this year, I started on low dose Valcyte (LDV), and like most people who try it, I had some immediate success. Most significantly, I starting getting some relief from my gut issues. The relief was great enough that I was able to stop all other medications that I was taking for this issue. In general, I could feel improvements from one week to the next on a variety of issues. I experienced a substantial increase in energy, which is apparently not uncommon when starting Valcyte; as I have mentioned elsewhere, this energy increase was well known back in the days before Valcyte, when IV ganciclovir was used. It appears to be most pronounced in the early days of treatment.
Occasionally, what I have termed the pro-inflammatory effects of Valcyte - the NMDA agonist effects - would start to predominate, and I would need to take a temporary break from the drug, and/or space out the doses more. After a while, I was always able to resume the previous dose.
I have found the work of Drs. Ian Lipkin and Mady Hornig to be exceptionally useful in understanding what is happening in this illness. It coincides with my own experience perfectly. My own experience points to one possible mechanism that helps explain why this illness becomes more difficult to treat over time. Lipkin and Hornig described how the immune system appears to burn itself out after the first few years of the illness. From what I have seen, this process appears to lead to a cascading effect among various bodily systems, causing them to enter a failure mode whereby they operate at only a fraction of their normal levels. The mitochondrial energy system is a good example of this. This failure mode also seems to be self-perpetuating, so that addressing the original insult to the body does not fix the collateral damage that accumulates over the years. This would seem to be a major reason why this illness is so hard to treat, and why a successful treatment of someone who has been ill for a long time requires a multi-pronged approach. One concrete example of this is that Valcyte can sometimes return people to full health in the early years of this illness, but in later years, it needs to be part of a comprehensive program addressing all aspects of this illness.
I'll use my own experience as an example here. In the early years of my illness (actually the years shortly following my final relapse), I took Valcyte at the standard 900 mg/day, starting several months after a successful seven-week course of IV ganciclovir. (I did the ganciclovir treatment because Valcyte was not available yet.) I had very great benefits from these drugs, and they led me to the greatest point of recovery that I have attained yet. (I should reiterate here that I have never tested positive for any active herpes virus infections at any point in my illness.) In the time between when my final relapse occurred (in September, 1998) and my ganciclovir treatments began in April of 2001, I experienced moderately bad headaches and low grade fevers every day. I was on the maximum dose of Tylenol during this 2.5 year period. The ganciclovir treatments got rid of the headaches and the fever, among many other things. As long as I remained on the Valcyte, the fevers never returned. But if I stopped the Valcyte for more than two weeks, the fevers inevitably came back. Only after five years was I able to stop the Valcyte without having the fevers return. As I seemed to have obtained the maximum benefit from the Valcyte, I stopped it at this time.
My gut problems had started some months before this, and the Valcyte at the full dose had no effect on them. At that point, I had no reason to expect that it would. Over the succeeding years, I was able to keep my gut problems under control, largely with antibiotics, but this did accompany a gradual deterioration in my health, including a greatly increased sensitivity to an ever-expanding list of medicines.
My original experience with Valcyte has an interesting bearing on my more recent experience with low dose Valcyte. At first, I simply noticed some relief in my gut symptoms - something that standard dose Valcyte had been unable to do. Dr. Montoya has documented the immunomodulatory effects of Valcyte, and I believe that at the lower doses, it is easier for these to manifest, as there is less of a tendency for them to be overwhelmed by Valcyte's pro-inflammatory effects. After a while, I noticed that I started running a low-grade fever for the first time in years, but only when I was taking the Valcyte. I interpret this as my immune system starting to come back to life. Later, this fever persisted whether or not I was taking the Valcyte. Finally, the fever occurred only when I was
not taking the Valcyte - exactly what my experience had been when I had taken the full dose of Valcyte years before. Eventually, the fever disappeared, whether or not I was taking the Valcyte, which was also the end state of my taking this drug years before.
I interpret this as meaning that the low dose Valcyte initially kick-started my immune system, and eventually got it working normally. In other words, it was reversing the process described by Lipkin and Hornig, turning back the clock on this illness for me. Right now, my illness feels much more like it did in the initial years of full disability compared to the more recent years.
This does not all translate to an increase in functionality, however. In my initial years, I had less energy, and interestingly enough, my energy started to drop off in recent months. The most likely explanation I can think of is that I now have a healthy immune system running at normal speed, and the immune system is one of the biggest consumers of energy in the body. My mitochondrial dysfunction has not been addressed, and the imbalance here has led to the lack of energy. In recent years, my extreme drug sensitivity forced me to drop all the medications that I had found so useful for increasing mitochondrial function. However, with the overall success of the LDV, I found that my drug sensitivities were rapidly dropping away. Previously, I had lost the ability to take any amount of Provigil (down from 150 mg per day), and I was not able to take useful amounts of NT Factor or PQQ. Now I can once again take all of these, although I have to increase the doses gradually. Nevertheless, as just one example, as of tomorrow I will be on 75 mg/day of Provigil - half my former dose of a drug that I could not take at all for years - and my energy is beginning to return (as is partially evidenced by this huge post). Basically, LDV seems to be a very effective treatment for central sensitivity, and although LDV in itself does not appear to be able to relieve all symptoms of ME/CFS, it appears to normalize enough neurological functioning to allow a much wider range of treatments to be used in those who are very sensitive (such as myself).
The pro-inflammatory and anti-inflammatory actions of Valcyte appear to sometimes work side by side, occasionally producing interesting results. For example, when I had more energy at the beginning of the year, my sleep cycle was very messed up, and I was getting up in the middle of the afternoon. But even as my energy decreased, my sleep cycle normalized, and now I am getting up at around 10 a.m. - something I haven't been able to do in years. And now I am starting to get my energy back while still keeping the improved sleep cycle.
I would also like to address the issue of inhibition of microglial inflammation versus immunomodulatory function in the case of Valcyte. In accordance with what I have seen, and consistent with Occam's Razor, these do not appear to be two completely different phenomena. I have watched both myself and others take a wide range of doses of Valcyte, and I have noticed that the doses at which the anti-inflammatory effects kick in always seem to be the same doses at which the immunomodulatory effects kick in. This leads me to believe that the second are a manifestation of the first. Much remains to be learned about the connections between the CNS and the immune system, but everything we learn tends to point more and more to a tight connection between them. From this point of view, if the CNS is not working properly on a large enough scale, then the immune system won't either. Conversely, fixing the CNS at a fundamental enough level should help fix the immune system as well. This seems to correspond to what I have seen.
That's probably a lot more than you were expecting,
@nandixon, but Valcyte is the most complicated drug I have ever taken.
If enough anecdotal evidence for your low dosage Valcyte working in ME/CFS can be had, then assuming the benefit might be occurring relative to inappropriately activated microglia, this should be exactly in Jarred Younger's sphere of interest for a potential new study, clinical or otherwise:
This would be fantastic. More than anything else, I would like to get some qualified researchers interested in this topic. On one hand, I think it would be really useful to demonstrate that the positive benefits of Valcyte in ME/CFS occur regardless of whether there is an active herpes infection. Demonstrating this alone would make this very powerful drug available to a much wider proportion of the ME/CFS population.
The usefulness of LDV in inhibiting microglial inflammation would also have enormous implications, as it it seems to me that inappropriately activated microglia are one of the biggest problems in ME/CFS. Valcyte is not the only way to address this, but it seems to be one of the most effective. And the lower doses can be used to minimize adverse reactions.
I'm definitely interested in trying the 1/64 valganciclovir tablet dosing to see how it compares with the cimetidine. There might also be an additive or synergistic effect between the two as well.
This makes a lot of sense to me. For those of us who have been very ill, using Valcyte in combination with other effective drugs seems like a good way to proceed.
