Six Months Later…Viral Breakthrough

I recently had six month after treatment blood test to determine if I achieved a sustained viral response or SVR. The results came back today and the Hep C virus is back. My viral load is currently at 1 million IU/ml. This completely sucks. 18 months of interferon and ribavirin including 5 months of an experimental polymerase inhibitor RG7168 aka RO5024048 that produced the side effects of weight loss, depression, inability to concentrate, lack of energy, memory going to hell, anemia, and I'm sure others, that the memory problems prevent me from remembering; all of this to achieve nothing. It is getting hit by the million pound shit-hammer all over again.

 I knew at the beginning that the traditional therapy only resulted in a 45% chance of clearing the virus. So when I had the chance to get into the trial of the RG 7128 aka RO5024048 polymerase inhibitor which, in early-stage experiments had demonstrated a rate of clearing the virus of up to 75%, I jumped at it. I'd hoped that the experimental drug would clear the virus. Even after the viral breakthrough that resulted in my expulsion from the test group I still thought that transitioning to standard therapy after the initial success of the experimental drug might give me a small leg up on clearing the virus.

Perhaps the fact that it took 12 weeks for the traditional interferon/ribavirin therapy to bring my viral load down from only 40,000 IU/ml to clear should have tipped me off. Maybe it should have shown me  that the strain of virus that I have would be resistant to my own immune system and traditional therapy and I would perhaps be more likely not to clear the virus then to succeed, but no one wants to face that possibility. When you have already been in a process for six months and you've already faced the side effects and found that, to a point, you can handle them; and you believe you have a chance of clearing the virus; and you don’t know what your health insurance is going to be like in another year or two or whenever a new therapy might come online; and the fact that you have insurance now; and you’re stubborn and you're optimistic; it all puts you in a mind to say I'm going to see if sticking this out will succeed in bringing me to a sustained viral response and a cure.

Well it didn't. So in a sense I look at the last two years of my life, the 18 months on the therapy and the six months beginning to recover from it until the day of the test, as being wasted. I did not get much accomplished during those two years. While I was able to do very good things at work (including expanding the scope of my operation, systematizing and streamlining all of the processes, integrating a part-time person and training them in handling the basics of the operation, and increasing sales and average of 25% per year), that is cold comfort. Just doing that, just functioning on a day-to-day basis and going to my job eventually took so much energy that it left little time and little energy for any part of a personal life. My work and efforts as a sculptor were minimal, my ability to do things with my friends and family were cut way down by the fact that it was exhausting to do anything for very much time at all. It all infuriates me even though I knew that it was only a 50% chance at success. I don't think anyone ever enters a situation like this thinking that they're going to fail and I certainly didn't. The fact that the therapy did not work leaves me feeling somehow cheated. It's not rational, but there it is. You feel that if you spent that much time, that much energy (or lack of it) invested that much hope and effort, something better should have happened. It didn't and I feel somehow empty.

All that being said, on the good side all my liver functions are normal. My doctors tell me that the results that they're getting from the liver tests would indicate that the time that I spent clear of the virus during the therapy, (which totaled about 12 to 14 months out of the 18), allowed my liver to begin to heal itself. The swelling is reduced. It is functioning well and I have bought additional time with a healthy liver. I also learned that I can handle the therapy. I learned that the side effects I got with the standard interferon ribavirin  chemotherapy and with the RG7128 are ones that I can manage. I know that a lot of people have a much more difficult time than I ever did during the traditional therapy. There are people who are so exhausted they can barely move; people whose anemia is frighteningly intense; people who have much more severe depression; people who lose even more weight than I did; people who have even less energy and people whose cognitive facilities and memory decline even further than mine. I realize that the ones who have it far worse than I did must feel even more empty or betrayed or depressed when they find out that it didn't work. Because as difficult as it was for me, if I had gone through even 12 months of the sort of difficulties that others with this disease undergoing the same therapy went through, I don't know if I could ever face doing it again.

 I'm sure at some point I will do it again. I don't like the idea of managing this disease. I don't like the idea of having something in my body that is gradually destroying my liver, breaking down my cognitive functions and creating in the long run a less energetic less mentally sharp individual. I don’t like the possibility of developing serious liver problems that might include liver cancer, cirrhosis and result in the need for a transplant. Though  my doctors told me that given my liver results I am the sort of person who is more likely to die with hepatitis C than from hepatitis C, I don't want to have it at all. The idea that a lifeless particle of protein wrapped around some DNA is working its way through my body destroying my liver doesn't fit my disposition. So I will try again at some point.

 I don't know that I will ever try interferon therapy again. It is extremely devastating and I don't know if I can face it even though I do suffer it better than many other people. There is a tremendous amount of research going on and a lot of that is oriented towards non-interferon drug combinations to attack the virus. There's a lot to look forward to and I know that I'm in good shape to see where it leads.

It's still depressing, it still sucks but you buck up and handle it the best you can. Even though I've been whining for most of this post, I know that my life is a hell of a lot better than a lot of other people in the world and especially a lot of other people with Hep C. Besides, Spring Training is right around the corner and how can you stay depressed when pitchers and catchers report in only six weeks,

Changes In Visualizations During Treatment

There is a great deal of evidence that creative visualization can influence the actual physical and mental performance of people in the real world. Studies have been done on academic test performance and athletic performance to use two examples and the evidence has indicated that if one group spends a specific amount of time visualizing successfully completing a task and another group spends the same amount of time practicing the task, the two groups have similar results upon undertaking the task. There is also evidence that the same sort of creative visualization influences recovery rates and treatment outcomes in disease situations.

It was with that in mind that I created my own visualization when I started HEP C treatment in the RG7128, RO5024048 clinical trial. I imagined that the polymerase inhibitor RG7128 was an armored division of fast moving powerful tanks that struck quickly and with lethal force at the HEP C virus. The interferon and Ribavirin were the methodical infantry units that followed the tanks and mopped up the remaining resistance from viruses that were either entrenched or bypassed by the fast moving armor. I visualized that image often throughout the clinical trial. After being tossed out of the clinical trial because of a viral breakthrough, my visualization metaphor changed. My tanks had run out of gas and were now abandoned by the side of the road.

After transitioning into Standard of Care therapy I still used a military image when I thought about my battle with the HEP C virus, but now it had switched to an image of slogging trench warfare with my infantry (interferon and Ribavirin) in hand-to-hand combat with the virus. It was going to be a 12 month struggle but they were attacking an already weakened foe and had strength of numbers and better supplies on their side. I used this image for several months and sure enough, after 14 weeks the numbers came back negative indicating my infantry were winning.

Then there was the possible viral breakthrough in December after six months of treatment and the subsequent return to being virally negative in January. The metaphor was fairly tattered by then but I tried to hold to it. As the months of treatment ground on and I eventually went on disability, the only military image that seemed to fit was the battle of Stalingrad; except I didn’t know which side I was on. Holding on till the end of treatment was the only concern. This carries on the military metaphor quite well actually. At the end of a long tour of duty on the front lines, the primary concern a soldier has is surviving until it is over.

At the end of treatment, the viral load was undetectable and the viral activity was negative so we can assume that the visualization was either successful and contributed to the treatment or at least did not inhibit the effectiveness of the treatment. I would recommend the technique to anyone undergoing any kind of treatment for disease. There is no need to use a military image, whatever is vivid and emotionally engaging will work. It is no doubt easier to maintain the metaphor for shorter treatments than longer ones, but anything that can help healing is worth pursuing. Just hope your metaphor doesn’t run out of gas on the side of the road. There is nothing sadder imaginarily speaking than watching your elite troops quit the battlefield.

Puzzling Evidence

Viral Load Blips Up and Then Back Down

What I feared came to pass at the end of December; I did indeed have a viral breakthrough. My viral load blipped up to 430 IU/ml. This is a relatively small number, though it is a log scale rise from the less than 43 that is undetectable.

It happened at the end of the year, during our open enrollment period when I was not sure whether I would still have the same insurance that would allow me to stay at California Pacific Medical Center (CPMC).

It happened while some of my health care team was taking some well-deserved time off from work.

It happened while I was scrambling to make sure I would have continuity in my medications as all my meds were running low. (While we are told at length not to let our prescriptions run low, the insurance companies will not let you renew expensive meds early.)

This led to three decisions about the disease.

One, there was not a follow-up test to determine whether the breakthrough was real or a false positive. No one knew whether I was going to be covered and no one wanted to be out of pocket the expense of a confirmatory test.

Two, Dr. Bzowej decided that it might be best to discontinue treatment. This was the second time I had a viral breakthrough at 24 weeks on two separate types of therapy (the RG7128 test and the Standard of Care therapy). She felt that I might be the sort of patient that needs 3-drug therapy.

Three, I had finally gotten my meds renewed just before my coverage changed and since I had a month’s worth of Interferon and Ribavirin left, I thought that I might as well keep taking it until it was gone. There was also a brief period of time when I thought I would continue at CPMC, so I thought that I should keeping taking it until the monthly test at the end of January and see what was happening.

I kept up my medication schedule through the month. Though by the end of January, I knew that I would not be covered for CPMC after February 1st, I went in for the viral load test anyway. By the time the results came back, my coverage had expired but the Nurse Practitioner at CPMC, bless her heart, called my with the results anyway. I was back to undetectable. Good news but what did that make the December test, true viral breakthrough (not good) or false positive (not bad)? We’ll never know

When I started at Kaiser, they tested my viral load on February 10^th. I came back undetectable in that one as well, though they said there was qualitative detection. That means that there is some evidence that there is still viral activity, but it is so low that it cannot be counted. I am not completely sure what that portends as depending on what you read it is either very bad or indeterminate.

I have been keeping to the medication schedule and go in tomorrow for another viral load test. We’ll keep moving forward.

As a final note, the TV show Royal Pains comes back this summer for another season. Write in and let the producers know we want to see more of “Fisherman Jim” so we can follow the course of his treatment for Hepatitis C. I believe he is the only character on a prime-time TV show with Hep C. I hope he recovers well on the show, but given that he is still running a fishing boat while undergoing interferon and ribavirin treatment, he sure makes me feel like a wuss. That’s the magic of television…

A Creeping Sense of Dread

Holiday Stress Equals Erratic Meds


I’ve been in treatment for 57 weeks and have been negative since the end of September, but I am approaching my upcoming viral load test with a great deal of trepidation. The month since the last test has been very difficult. The holidays were not a happy time for my wife and I as there were job problems, family problems and the general high stress levels that the holidays can bring.

The combination of all the stress with my growing inability to concentrate and remember resulted in my missing 3 afternoon doses of my meds during the 10 day period following Christmas. This makes me very edgy as it was the combination of skipped interferon and lowered Ribavirin doses that led to the viral breakthrough that bounced me out of the RO5024048, RG7128 study last June.

In this case, I did not miss any interferon doses, but I did miss 3 partial doses of Ribavirin in a relatively short period of time. This was effectively similar to the lowered Ribavirin doses of late May before the breakthrough. Ribavirin by itself does not seem to have a strong direct antiviral effect on the Hep C virus, but it does contribute a great deal to continuing to hold the virus in check once the interferon has pounded it into undetectability. Therefore reducing the dose, whether deliberately or through simply forgetting to take the drug, can have a significant negative effect on continuing to be undetectable.

The strange thing is that I cannot remember forgetting to take two of the doses (I realize how silly that sounds given the state of my brain by this point but nonetheless…). I can only remember the sick feeling of getting up the next morning, going to take my meds and finding the closed container labeled Monday p.m. that still contained my previous evenings dose. It was bad enough the first time, but two days later on Thursday, exactly the same thing happened. I thought I had done my duty, got up the next morning and found the container with the dose on the table. I knew that it was serious, that I had to stay on schedule and yet I had forgotten again. The thing that knots your stomach is the knowledge that you have screwed up and you can’t go back and make it right. The opportunity to stay on the schedule is gone and the best you can hope for is that it hasn’t compromised your treatment.

Several days later, I missed the third evening dose. This time I figured out what happened and decided that yet another behavior modification was necessary. I went to take my evening dose, sat down and opened the container with the meds in it and then my cell phone rang. It was someone to whom I rent space in my studio so I took the call. It took a while to figure out the problem and by that time I had forgotten to take the dose. However, since I had specifically gone into the room to TAKE the dose, when I thought about it later that evening, I confabulated the memory of actually taking the meds. Again, the increasingly sick feeling in the morning when I found the open but full container on the table. I decided at that point that I would immediately take my doses the moment I thought of them from that point on and it has worked excellently since then. It doesn’t matter if the phone rings, my wife is talking to me or I have to run to the bathroom; when the thought of my evening dose crosses my mind, I get up right then and go take it.

I cannot stress enough the importance of keeping your dosing schedule (your doctors, nurses and everyone else all stress the same thing, so I know I am preaching to the choir). If you have to put signs all over your home, rubber bands on your wrist or tattoo it to your forehead; do whatever it takes to stay on your schedule and not miss a dose.

I hope it doesn’t screw me up, but it was a bad end to last year and a tough start to this one, so I am looking at this test the same way you look at the door into the dark basement in the horror movie – don’t go down there and don’t split up.

Latest Viral Load Count – So Close…

When I checked the mailbox on the way home from work today, the envelope with my latest test results was there. The other two envelopes were my paycheck and my wife’s paycheck, but I didn’t register that until later. I wasn’t thinking about money. The only thing I was thinking about was whether those results would show my viral load was undetectable.

In situations like these (preparing to open the envelope bearing important news), you find that you’re still mentally a primitve creature. I’m not a god-botherer, as the Brits would say, but as I walked in the house I was chanting to myself, “Yes, this is it. Please be undetectable. Yes, this is the week. Come on, let’s see undetectable results.” I sat down at the kitchen table (okay, it was the table on the back porch but you get the picture), held the envelope, took a deep breath and opened it up.

My viral load numbers since the viral breakthrough have been: 40.000; 10,000; 5,000; 1,500; 990; 310 and 110 IU/ml. I was really hoping that I would get that final bump down but it didn’t quite happen. The number was 60 IU/ml. Undetectable on this test is 43. It’s been 13 weeks since I went back on full interferon dosing after the breakthrough and I’m not quite there yet. Seventeen of those little bits of viral DNA per milliliter are still hanging on in various nooks and crannies of my bloodstream.

Objectively, this is not the best news. The longer it takes you to reach undetectable levels the lower your percentage of having a sustained viral response at the end of your chemotherapy. But I’m going to keep the same attitude that I had at the beginning of the RO5024048 polymerase inhibitor trial just under ten months ago. Back then I refused to believe that I would not get the test drug and would end up in the placebo arm of the trial. Now, I refuse to believe that I will not be one of the 25% or so who obtain an SVR as slower responders.

I’m not as stubborn as my wife’s Irish ancestry allows her to be, but I have my own stubborn Polish fatalism going for me and I’m going to ride it to the finish. Primitive mentality yes, but it’s the only one I have.

A Nice Soft Belly

It turns out that my status as a research study participant who morphed into a standard of care hepatology patient created a bit of a black hole in my medical records. Since all of my records from the study are confidential the hepatology department discovered that even though I was 12 weeks into treatment, they did not have basic paperwork on me. To solve this problem, they brought me in for a meeting with another nurse practitioner, TL, to gather the necessary data. Unfortunately, they did not tell me why I was meeting with her and thus I left my medical history documents at home.

When I arrived, they handed me a twelve page questionnaire detailing my medical history, most of which I can never remember in normal circumstances much less when my brain is in a fog. It worked out well enough in the end as TL and I went through it together and puzzled out the details. It was reassuring as well that when I recounted the timeline of my study participation, dose reductions and subsequent viral breakthrough, TL was firmly convinced that the dose reductions were indeed the cause of the breakthrough. It is powerful reinforcement to hear another experienced person express the opinion that it was not the intractability of the virus that caused the problem, but rather the variability in dosage dictated by the study protocols. It reinforces my optimism going forward through the rest of the treatment.

TL informed me that the rest of the treatment would total nine additional months after I became undetectable. Given the nine months I have been on meds, it will make a total of 18 months of interferon, ribavirin and the other assorted drugs I am taking. It is going to be an even longer grind than I assumed at the beginning of the process lo those many months ago.

My viral load is down to 110 IU/ml. after twelve weeks and I am hoping to see it go undetectable (under 47 IU/ml.) in my next test on the 10th of September. That would put the end of my treatment in June of 2011 when I turn 58. If it works and I am still undetectable six months after the end of treatment, I will have gone from diagnosed to cleared of the virus in three years. A dream perhaps, but it’s the one I am sticking with.

The meeting ended up with TL adding some additional monthly blood draws to my schedule and a brief physical exam. TL checked my legs for swelling, listened to my lungs, checked for any rashes and then palpated my stomach to check for ascites. “Oh, you have a nice soft belly,” commented TL, “no evidence of fluids at all.”

That is the best medical comment I may have ever received. From this point forward, anyone who comments on what is left of my spare tire is going to be told that my medical team has complimented me on my soft belly and far be it for anyone else to criticize its texture. In fact, I am patting it now as I finish this missive, so soft…

Which Side Effects Matter…and to Whom

When you begin the process of considering whether to apply for a research drug trial or enter treatment, one of the things that you give a lot of thought to is the side effects that accompany the various drugs you will be taking. These side effects fall into two categories, the side effects that are physical symptoms affecting your comfort level and the side effects that directly alter your body’s operating systems. Those two types of side effects matter in very different ways to you and to the doctors and/or researchers supervising your treatment.

Those of us participating in a study or standard treatment tend to be very concerned with how the treatment is making us feel. The doctors tend to be very concerned with how the treatment is affecting our body’s ability to function. These concerns definitely overlap, but the primary focus is very different between patient and doctor.

When the patient first examines the information about experimental drug trials or the standard of care treatment, they tend to focus on the potential side effects of the medications and especially the side effects that manifest themselves as physical reactions: nausea, vomiting, diarrhea, fatigue, muscle pain, dizziness, headache, rash, irritability, hair loss, sore throat, depression, confusion, itching, etc. The patient also generally makes a note of the potential long-term side effects like changes in thyroid function that may be permanent and the possibility of macular degeneration. A lot of the patient’s focus is definitely on the comfort related side effects.

The doctors are aware of all these as well, but primarily as an issue of whether the patient will be able to continue through to the completion of the treatment. Will some of these become so serious that the patient will have to discontinue either the study, if they are in one, or the standard of care treatment? Can they be managed successfully to keep the patient on course?

The set of side effects of primary concern to the doctors are the ones that directly affect the body’s systems: Anemia (low red blood cell counts), Neutropenia (low white blood cell counts), thyroid function changes, depression and insomnia. Anemia can put stress on the heart and circulatory systems and contribute to fatigue; Neutropenia affects the body’s ability to fight off infection successfully; changes in thyroid function can lead to a host of metabolic problems; depression and insomnia can both lower the body’s ability to fight off disease and function successfully. For the patient in a research study, the side effects just mentioned can lead to the doses of their meds being reduced or suspended to the point that the treatment loses its effectiveness. That is unfortunately what happened to me. For the patient under standard of care treatment the doctor may be forced to prescribe additional drugs to counteract those effects in order to keep them on the course of treatment.

It was interesting to realize, after the fact, that the long list of side effects I was originally concerned about, were not the ones most important to my successful treatment. The nausea, chills, headaches, dizziness, irritability, rash, back pain and the rest were not, in the long run, the side effects that negatively effected my treatment. The tremendous reduction in my white and red blood cell counts were what required the reduction in my medication doses that eventually caused the viral breakthrough.

There wasn’t really anything I could have done about it given the requirements of the research study, but it is interesting to note, that I was looking the other way, so to speak, while the virus slipped back in…

Standard of Care Pace vs. Research Pace

I just got my latest viral load numbers back from the lab today. The viral load has declined to just a bit over 1500 I.U./ml. I have now achieved a log level reduction in viral load since the peak of the viral breakthrough. This is great news but also points up one of the biggest differences between being on the Standard of Care treatment of interferon and Ribavirin and the research trial treatment of interferon, Ribavirin and Polymerase Inhibitor RO5024048. The Hep C virus is definitely harder to kill on only two drugs instead of three.

My viral load progression on Standard of Care has been:

Week 1: 40,000 IU/ml. (peak number of viral breakthrough)
Week 2: 10,000 IU/ml
Week 5: 5,000 IU/ml
Week 7: 1,500 IU/ml (log 1.6 reduction)

My viral load progression on the Research Trial drug was:

Week 0: 12,900,000 IU/ml.
Week 1: 4,260 IU/ml (log 3.48 reduction)
Week 2: 1,110 IU/ml
Week 4: 195 IU/ml
Week 6: undetectable (log 5.83 reduction)

As you can see, the pace at which the virus is destroyed is much slower (though steady) on the interferon and Ribavirin combination. It has taken 6 weeks to get a log 1.6 reduction from the peak breakthrough number when it only took one week to get a log 3.5 reduction from my pre-trial viral load on the polymerase inhibitor. This has taken some getting used to. You get spoiled on the three drug therapy, especially in the case of the polymerase inhibitor because it does not seem to carry major additional side effects along with it. While I steadily heading towards the log 2 reduction in my viral load needed by week twelve after the breakthrough in order to continue treatment, it seems to be happening in slow motion after the knockout blow the RO5024048 dealt the virus while I was on the three drug combination.

While this may pose a few psychological issues for me to deal with, the overall outlook for the polymerase inhibitor plus interferon and Ribavirin mode of treatment is very good. It definitely deals a hammer blow to the virus and so far, most of the individuals I have talked to who are in the trial (admittedly a very small sample) have not reported serious side effects associated with the RO5024048. Also the addition of a new group to the trial which will receive the drug for 24 weeks instead of the 8-12 weeks we got it indicates that the safety issues are not a major concern and that the drug is promising enough to expand the range of patients eligible. This is all very good news for people both awaiting treatment and considering their treatment options. Another effective tool appears to be on the way in the battle against the Hep C virus.

Viral Load and Log Numbers

Viral Load is one of the numbers that folks with Hepatitis C take very seriously. We take it more seriously than we probably should given that the viral load numbers do not directly correlate with whether you are symptomatic, the amount of damage to your liver or the seriousness of the side effects that you may be experiencing. It is, however, the number that is measured to determine the ongoing success of your treatment regimen and to determine in the long run whether you have cleared your body of the virus. Given that, it is followed with a great deal of attention.

The viral load is expressed in the number of copies of the Hep C Virus RNA that are contained in a milliliter (ml) of blood. This is expressed as the number international units (IU) of Hep C RNA per ml. In my case, my viral load number ranged from 3,000,000 IU per ml when I was diagnosed to just slightly below 13,000,000 IU/ml at the onset of treatment.

The changes in viral load that we track during treatment are expressed as logarithmic or log numbers. Log number differences in the amount of virus are differences in amount that are expressed as factors of 10. These log number differences are the numbers that are considered significant in Hepatitis C treatment. Using my case as an example, if 13,000,000 IU/ml is my viral load at the start of treatment, then a drop in viral load to 1,300,000 is a log 1 change. A drop to 130,000 is a log 2 change, to 13,000 is a log 3 change, 1,300 is log 4, 130 is log 5 and going to undetectable, or under 15, is right about a log 6 change in viral load. In treatment, the doctors want to see a log 2 drop in viral load by week 12 or the patient is considered to be non-responsive.

Once we understand that, the changes in viral load that we see at various times during our disease and during treatment and the significance of those changes become easier to understand. For example, the changes in my viral load as I progressed from 3,000,000 to 13,000,000 before starting treatment are actually not significant changes despite the fact that they look like large changes. In order to have a log 1 increase in my viral load, I would have had to see it increase to 30,000,000 and a log 2 increase would mean that I would have had to see a viral load number of 300,000,000 IU/ml. Now that would be a high viral load indeed. Likewise if you had a viral load of 250,000 and saw it jump to 500,000 it would be considered a not significant change in amount even though your viral load doubled.

The same thing applies to watching viral load as it drops. If you have that same 250,000 IU/ml at the beginning of treatment, a log 1 drop would require a change to 25,000 and to achieve the log 2 reduction your doctors will want to see by week 12 you need a drop to 2,500 IU/ml. In order to reach the undetectable level, you would need a drop of somewhat over log 4. In my case, when I went from 13,000,000 to 4,000 after one week of treatment, that was over a log 3.5 drop in viral load. Likewise when I had my viral breakthrough and went from under 15 to 17,000 it was about a log 3.1 increase in my viral load.

Both of these numbers were significant because of the size of the logarithmic change in the amount. When my confirmation breakthrough test came back with a number of 40,000 that was not a significant change from the 17,000 number that signaled my viral breakthrough despite the fact that it doubled. When the first test results I got after going on treatment outside the study came back at 10,000 that was also not a significant change. I was happy to see my number going down, but just to get to a simple log 1 change I would have to drop to 4,000 and the magic log 2 change means I have to drop to 400 IU/ml.

So don’t panic over fluctuations in your viral load numbers that might appear to be quite large if they don’t reach the level of a ten-fold (log 1) change or greater. Even then, it may not be signaling a major change in your illness, but if it doesn’t even reach that level, it probably means little or nothing at all…

Why Did I Continue Treatment…

Somebody asked the other day about what the thought process was that resulted in the decision to continue treatment in the face of a viral breakthrough roughly 6 months after the RO5024048 study began. It’s a good question and thinking about the answer made me thoroughly examine why I did decide to go on. After all, why not take a break after 6 months of side effects and wait for new drugs to come online?

It started with the positive initial results I had in the study. My viral load dropped from 13,000,000 to 4,000 (about a log 3.5 drop) in the first week of the study. That’s a pretty impressive result from 7 days of treatment and I was at 195 after 4 weeks of the study. Since I did not become undetectable (less than 15 which is the limit of the test’s detection) at week 4, I was did not have a Rapid Viral Response (RVR) but rather an Early Viral Response or EVR. An RVR means that in the general statistics of Hep C treatment you have about a 60% chance of clearing the virus (also known as a sustained viral response or SVR). An EVR puts you in the 40% range. While these are the cold hard statistics garnered throughout the history of Hep C treatment, the early results for the experimental drug RO5024048, which I believe I was taking, indicate the possibility of a 70% clearing rate. I was undetectable after my 6th week viral load test which means I reached that stage sometime between the 28th and 42nd day of treatment. For all I know my viral load dropped to undetectable the day after my 4th week test putting me tantalizingly close to the RVR cutoff. Sure it’s whistling past the graveyard to think that, but let me carry some illusions through this process.

Both I am my doctors are fairly well convinced that the viral breakthrough was the result of the dose adjustments in my interferon that were mandated by the research protocols. Treatment outside the study under the Standard of Care for Hep C gives me the opportunity to undergo the course of treatment at the full doses of interferon and Ribavirin. This gives the treatment the best chance of working for me.

I was at an undetectable viral load for somewhere around 18 weeks. During this time, my liver enzymes returned to normal and all my liver tests returned results in the normal range. They tell me that this means the inflammation in my liver has subsided and it has had at least a small window of time to begin a bit of healing. My liver disease was between a stage one and two and giving it time to heal will give me a much longer timeframe for the progress of the damage. If continuing treatment returns me to an undetectable level for another 20 plus weeks, this just can’t be a bad thing for my liver.

All things considered, I tolerate the treatment well. I have side effects and some are worse than others, but compared to the treatment issues that many other patients have it is pretty reasonable. I am continuing to work, albeit at a reduced level of hours. I able to keep what food I eat down through the occasional wave of nausea. The flu-like symptoms follow a reasonably predictable cycle and do not overwhelm me. Insomnia is an ongoing issue, but when it gets particularly intrusive, I have drugs that allow me to sleep without a sedative hangover. The most insidious effect the treatment had on me was the gradual onset of depression. However the deployment of antidepressant medication has made that a manageable issue as well. So if I can tolerate the treatment, why not continue to be aggressive in attacking the virus.

My employment situation is good. Both my boss and the Executive Director of the organization are firmly in my corner and are willing to work with me to create a situation which gives me the best chance to do my job and gives the organization some actual benefit from my continuing to work. There is no guarantee that this level of support will continue indefinitely. Either of the individuals might move on or retire and their replacements might not be as supportive.

My benefits are good. My employer pays for my health plan and the plan I have allows access to the CPMC Hepatology Center which has first-rate doctors and is on the leading edge in both treatment and research. I still have accumulated sick time I can use (though every time I look the number seems to have shrunk a lot more quickly than I thought it would) and my organization allows other employees to donate sick time to me. Luckily, I haven’t alienated everyone in the organization yet and several people (who seem to be frighteningly healthy) have offered to donate time to me. Again, this is the sort of thing you can’t count on being there forever, so why not take advantage of it while I can.

I have a pretty grim view of the financial future of the USA. What with huge deficits and unfunded liabilities; high unemployment, several more years of the housing mess in front of us, the treasury printing trillions of new dollars, the states being for all practical purposes bankrupt, etc, etc, etc, I figure I should go for the treatment while I can afford to do it.

Finally, I have the full support of my wife. She has been absolutely unflinching in her support throughout this process. After we talked about all the reasons for and against continuing, she supported the decision to go ahead and continues to believe along with me, that we are going to beat this virus. After all, it’s not even really alive. It’s just a protein coat with some RNA, damn it and if we can’t even beat something that doesn’t even meet the complete definition of being actually alive, what chance do we have…

The Cost of Stress

The results of the first viral load test since I began treatment outside the study came back yesterday and my viral load numbers are trending back down. This is enormously good news. The first test indicating the viral breakthrough showed a viral load of 17,000. The retest number was a touch above 40,000. Now, one month after the initial breakthrough and two weeks after resuming full doses of interferon, the number has dropped to 10,000. This offers confirming evidence for the theory that the breakthrough resulted from the series of reduced and interrupted doses over the final few months of my participation in the study and not because the Hepatitis C virus had begun to develop resistance to interferon. This also adds weight to the belief that it is indeed worthwhile to continue treatment and potentially clear the virus.

Tracing the path of stress during the past month leading up to this result has been a learning experience of the first order. The initial news of the breakthrough brought a tremendous jolt of adrenaline and anxiety. I was convinced the breakthrough had everything to do with the interferon dosing changes due to my low neutrophil counts and was intent on continuing treatment in some form. The uncertainty of whether or not the study doctors and my doctors would agree and what this would mean for ongoing relations with the researchers resulted in a solid seven days of anxiety. The agreement and support of the doctors involved was an all-too-brief relief as the stress shifted to getting rapid treatment and prescription authorizations from the health insurance company and attempting to secure bridge doses of interferon and ribavirin that would allow no further dose interruptions until the prescriptions were filled. Having accomplished that, the stress shifted to finding the best suppliers for the prescriptions which would result in the lowest possible co-payments so as to make ongoing treatment affordable. Finally, the wait for the first round of tests indicating whether the renewal of full-dose interferon treatment would knock the viral load back down continued the grind.

The first 10 days were actually a period of relatively high-energy as news was received, reactions were dealt with, research was done, meetings were planned for, calls were made and decisions were arrived at. The next 10 days were a marathon of waiting for authorizations, arranging prescriptions and deliveries and generally feeling my physical and mental energy drain away. The final days were a series of forced marches through each day. It became hard to sleep and harder to stay awake. I woke up tired, had to take several catnaps a day at my job to be able to keep any mental focus at all and when not at work found myself falling asleep after any activity that required mental effort.

The relief of seeing the new viral load numbers bestowed the great gift of sleeping through the night for the first time in weeks; and sleeping through the following day, and continuing to doze off throughout the day today. Who knows, a few more days of 16 hours of sleep and I might be able to watch the knock-out round of the World Cup with the attention it deserves.

The Rest of the Story…

What really happened when I formally left the study was, needless to say, much less histrionic, though it had its own brand of drama.

I got a call from AVB in the morning announcing the lab results were back, I had a confirmed viral breakthrough and I had to stop taking the meds belonging to the research study. She was working on getting some medical samples from the Roche representative that would bridge me over until my insurance authorizations went through and my prescriptions for Pegasys and Ribavirin were filled. She told me that when she had some news she would contact me and then I could bring my old meds in and get the bridge meds from her.

Sure enough the call came through at 3:00 p.m. that same day while I was in an event planning meeting. She had arranged the bridge meds and could I get to the hepatology research center no later than 4:30 to pick them up and drop off the old stuff. I was without transportation, but promised to do my best. I excused myself from the meeting by telling everyone I had to go pick up drugs and started walking quickly the 1 ½ miles to my home.

As anyone in San Francisco who relies on the Municipal Railroad system, or MUNI as it is infamously known, schedules are something that are mostly honored in their breach. I walked the distance home along a MUNI route without seeing a bus during the entire 40 minutes. I grabbed my meds, diary, sharps container and fanny pack jumped in my trusty pickup and headed back toward the research center. I went back over the same route and still did not see a bus by the time I had to turn off on other streets.

When I got to the center, I met AVB and she collected my old meds and other materials. I actually got to keep my Roche Logowear. She explained that she had samples of Ribavirin and Pegasys that should tide me over until the insurance authorizations cleared and that she was on her way to Dr. B’s office (who had stayed late to be available) to get the necessary documents signed. She returned with the meds and with the gentleman who would be the nurse coordination for my treatment with Dr. B. She introduced us; he gave me his contact info and he told me he would be in touch with a day or two to follow up on the authorization status. He gave me some lab test request sheets and a preliminary schedule of when I needed to get lab tests done. The he shook my hand and, wished me good luck and said he would contact me soon.

AVB then went over the kit of materials that is given to outpatient treatment subjects and showed me how to use the preloaded syringes that the Pegasys came in. No more vials to fill syringes from, Yay!

At that point she wished me good luck, said that she was still available as well if I had questions or needed to go over any of my previous history on the study. She choked up a bit. I choked up a bit. I thanked her for all the efforts she had made on my behalf, she said don’t worry about that now, just work on having a successful treatment. We shook hands and she put her arm on my shoulder and walked me down the hall to say good-bye.

And that’s the Rest Of The Story…(apologies to Paul Harvey)

Drummed Out of the Study

The confirmatory test results came in and I got the phone call from AVB formally telling me that I had a viral breakthrough and as per the protocols of the research trial must be taken off research treatment. I was asked to come in with my unused meds and my records.

I gathered together my bottles of Ribavirin both empty and full, my sharps container with all my used syringes, my unused vials of interferon in my insulated Roche fanny pack, my diary with records of the timing and amount of my daily doses of meds, loaded them into a bag and drove to the CPMC hepatology research center.

I trudged, gasping, up the hill to the hospital, rode alone in the clanking elevator to the third floor and was escorted into one of the closet-sized examining rooms. I stood in front of the desk of research coordinator AVB and unloaded my bag. The vials were counted, the pills were counted, the sharps container set aside for the later counting of the used syringes and my never-to-be completed dosing diary was confiscated from me. The Roche logo was ceremoniously cut off my insulated fanny-pack and it was tossed back to me. I was slapped on each cheek with the partially completed diary and as the theme song to Branded played in the background I was marched out of the room. As I walked down the hallway towards the elevator the nurses averted their eyes, the lab tech closed his door and the other patients behaved as though I did not exist. The walk back to my truck became another endless, gasping, uphill climb. What shreds of my dignity I had managed to preserve until that time broke down when I got into my vehicle and I sobbed uncontrollably over the steering wheel until I could gather what composure I could and drive back across the pitiless city to my cold, echoing home.

Tomorrow…The Rest of The Story.

Bad/Good News 3 – Participating in Future Research Trials

The final item that concerned me about moving out of the research trial and getting treatment through standard channels is one that will concern anyone in the same situation. Does making this decision preclude you from participating in future research trials?

I specifically asked AVB, the research coordinator about that issue. I framed the question to her that “since I am dropping out of the trial to pursue treatment outside the protocols and on my own…” She immediately cut me off at that point. Her statement to me was that I was not dropping out of the study. I was consulting with the medical personnel in the study and my own doctors and making a decision about what was in my best interests as a patient. This decision transcends the study and is about what is best for the patient in their attempt to fight their disease as effectively as possible.

She stated that I have followed all the protocols, come to all appointments, kept accurate records and come in for additional testing as the situation required. Patients who have done these things are considered to be good research subjects. That fact that patients who have been reliable subjects make decisions to pursue courses in the best interests of their long-term health does not preclude them from being included in further studies. She stated that given a history of positive participation in previous trials she would be inclined to include them in future studies for which they passed the screening.

She mentioned that their have been people who have dropped out of this and other studies she has been involved in either due to viral breakthroughs, inability to tolerate side effects or inability to follow the study protocols. Some of these patients have cut off all communication with the study, not returning phone calls, emails and letters and not returning the unused study medications. In some cases they cannot be found and their ongoing health cannot be determined. These are the sorts of patients she would not include in any future trial. They are not reliable subjects.

This was a load off my mind as my percentages are low to clear the virus on continued treatment. While Telaprevir will no doubt be approved soon, there is not guarantee that I would succeed with it either and having the possibility to participate in trials of future promising treatments is another arrow in the quiver, so to speak.

The only real downside is that I am no longer treatment-naive…

Bad News is Not So Bad 2

The Kindness of Doctors.

All of us who have being living in the American health care system have stories of the system letting people down. Doctors who sleepwalk through their job; insurance companies that find any way possible to deny care; nurses who are surly and hostile; hospitals that warehouse and ignore patients. After a lifetime of these kinds of events, you can become fairly cynical about the motives of healthcare professionals and about their dedication to their jobs and those under their care. The response that has been shown by the folks in the Roche RO5024048 study is the kind of event that can restore your faith in doctors.

In the first phone call to me informing me that I had had a viral breakthrough, AVB the study coordinator told me that I should ask Doctor B, the hepatologist, what she thought about my continuing treatment outside the study protocol. She said there were no guarantees, but I should certainly ask the question. I did not have a lot of confidence in Doctor B’s response. She is the lead doctor on the study. She gets her name on the research paper written about the study and in the interests of gaining research data for the study putting me off-protocol does not help her do that.

When we had our meeting just after the retest blood draws, she went over the viral breakthrough test results and mentioned that, subject to the results of these tests, I would be off the research treatments. AVB mentioned that I had a question for her and I asked about continuing treatment outside the study. Doctor B wanted to look at me test results and most particularly my dosing record. We she examined them in detail and saw that the breakthrough had occurred after 2 skipped doses of interferon due to low neutrophil counts and that I had been on a reduced interferon dose for several weeks before that, her whole personal affect changed. It was a subtle shift from researcher to doctor. She looked closely at my viral load numbers and saw that I had been undetectable for between 12 and 18 weeks even on the reduced dosing and that the dose reductions had all been due to low neutrophil counts (neutropenia). She asked me how I had been handling treatment and the treatment side effects. She told me that outside the research study protocol, she could administer drugs to combat both the neutropenia and the lowered hemoglobin counts. This would allow me to have a good chance to continue treatment on the full doses of interferon and ribavirin, thus giving me the best chance to clear the virus. She mentioned that other drugs were in the pipeline and nearing approval, particularly telaprevir, and did I think I wanted to wait or to continue with treatment now.

I told her I was leaning toward continuing treatment now, but wanted to talk to doctor C, my gastroenterologist before I made my final decision. She immediately told me that she would call him and let him know the latest situation and that I should talk to him and my primary care person as soon as possible so as to be able to get the treatment drug approval process under way with the insurance company as soon as possible. She also volunteered to oversee my treatment if I got a referral to her from my primary care doctor. She also volunteered to call him as well and let him know the situation.

To see the change in view from research scientist to medical doctor determining the best course of care for her patient caught me completely off-guard. It seemed to occur in a matter of an eye-blink. She became completely focused on letting me know the options and the possibilities. It gives me a great deal of confidence in having her as my hepatologist going forward.

My conversation with Doctor C was similar. He wanted to know if I felt I could handle treatment going forward. He also wanted me to know that the percentages of clearing after an event like this are not high. He also emphasized the availability of the drugs to treat the low blood cell counts and the fact that this would allow the higher doses of the Hep C Standard of Care drugs. But the decision is always in my hands.

I am going forward with treatment. It may take a few weeks to get everything set up, but the test results don’t come back until after my usual dosing schedule, so I will have one last dose in my from the Roche study before I forge ahead on my own.

Just as a final note and reality check, I had a meeting with my primary Doctor K. I have some thyroid function issues due to treatment and he needed to prescribe something for that and issue the referral to Doctor B for insurance company purposes. Ah, the reality of being back in the arms of my overworked primary care doctor. Listen, no chance, talk over me, of course, give me confusing instructions, par for the course. It’s good to know something things don’t change…

Bad News Is Not So Bad News 1

The situation of having a viral breakthrough and the decisions made about treatment in light of that breakthrough is a good illustration of the differences between undergoing treatment under the protocols of a drug trial and undergoing treatment under the Standard Of Care supervised by a hepatologist. There is a bit about that is this post.

I met with Doctor B, the doctor in charge of the Roche RO5024048 study today. I was getting the blood tests to confirm that I indeed had a viral breakthrough and met with her as part of that process. Given that it would be highly unusual for the tests to show that I was again undetectable, I am going to be dropped from treatment under the protocols of the study (the protocol is that if you show any viral activity at week 24, treatment is suspended). That being the case, I asked Dr. B what her opinion was of the value of my continuing outside the study using the standard interferon and ribavirin treatment.

She was initially noncommittal and wanted to see my viral load history and my dosing history for the Pegasys and ribavirin. She saw that my viral load had been undetectable for 18 weeks. She also saw that I had spent 5 weeks on a ¾ dose of interferon, had skipped 2 doses completely due to low neutrophil counts and had just resumed injecting at a ½ dose level. I had also been on a reduced dose of ribavirin for the past 7 weeks. When she saw that the breakthrough had occurred after the two skipped doses of interferon, she warmed to the idea. She asked me how I have been tolerating the treatment. I told her I had a lot of the usual side effects but that the addition of an antidepressant had really made a huge difference in my mental outlook and my mental energy. Then she pointed out the reasons she thought it might be worthwhile to pursue.

If you undergo treatment under normal circumstances, you can be prescribed drugs to reduce the loss of neutrophils (neutropenia). You can also be prescribed meds to help with the hemoglobin loss as well. They don’t do this in drug trials because they are trying to control the number of variables as well as to determine the effect the study meds are having with the interference of other drugs. Being able to take these additional medications means that the full doses of interferon and ribavirin can be maintained for the longest possible time during the course of treatment. It goes without saying that this increases the chances for a successful outcome.

In my case for about 40 % of the time I have been in the study, I have been taking reduced doses of just those standard medicines that have proven so successful against Hep C. Moving forward with treatment under full doses means I have a chance to reach a successful outcome. Given the 6 months I have spent on this so far, I don’t see why I shouldn’t grab that chance.

Thoughts From The Nail

The shock of having a viral breakthrough is wearing off. I have spent some considerable time today mulling over the implications of the virus returning. For anyone in this situation, there are a number of considerations and possibilities.

Is there something that presents itself as a reason that the breakthrough might have happened? Does it appear to have happened despite your best efforts to adhere to the protocol? If it happened in spite of you taking all you meds correctly, your virus might be developing a resistance to the type of interferon you are taking or to interferon in general. There is evidence that changing the brand of pegylated interferon you are taking can change the results against the virus. You can talk to your doctor about the possibility of changing the type of interferon you are taking. Of course some insurance plans only include one company’s pegylated interferon in their formulary which means you are out of luck unless you have the $500+ per dose to cover the change.

I believe there was a specific reason for my breakthrough. I think it resulted from dose adjustments made to my interferon dose dictated by the study protocols. These dose adjustments happen to many patients who are undergoing treatment. They are made to attempt to control side effects for the most part. If your hemoglobin drops, if your neutrophil or lymphocyte counts drop too far a dose adjustment will be made in your interferon or ribavirin. In my case, they reduced my Ribavirin dose from 1200 mg to 1000 mg per day after a week 16 retest showed my hemoglobin had dropped to 9.6. I don’t think this had much to do with it. More importantly, at week 21 my neutrophil count went down to 360 and I was told to skip my interferon dose. The next week the count had not rebounded quite far enough and I had to skip another dose. I had only injected one time before my week 24 tests and that was a half dose. I think the suspension of my interferon for two weeks directly contributed to the viral breakthrough.

Which way is you viral load trending? If you have a breakthrough, they are going to retest you to reconfirm that it is a real event. It could be a lab error, especially if it just blips a bit over the undetectable level, or it could be a one-time event. If the results show that your breakthrough is real and the viral load is rising, you’ve probably got a resistant virus and will need to change your treatment drugs or dosing. If your breakthrough is real, but the viral load is declining, then the continuation of your present treatment regimen might mean you will return to the undetectable level. If the results show you are again undetectable, then perhaps it was a test error or one-time event and you can curse the additional gray hair you got while waiting for the results.

Is adjusting your dosing possible? If your breakthrough occurred after lowering your doses of medications, is it possible to raise them again and safely manage the side effects? Did the side effects, especially the blood counts, mean you absolutely had to reduce the dose?

Do you have the option of continuing treatment through your own insurance or by funding it yourself, or is being in a study the only way you can afford treatment?

Does a viral breakthrough mean you are starting over from week one of the 48 week treatment regimen or, if your viral load is trending downward again, would it mean only a continuation to the end of the original treatment time-frame?

All these are questions to ponder. You can endlessly mull them over in your mind right away, or you can try to get away from them for a bit and start to obsess about them when your get your retest results.

I tend more toward the drive yourself crazy by obsessing about them continuously camp. Luckily I have a bunch of drugs to calm me down and help me sleep, otherwise by late next week, I would be a mere husk of myself. Try not to go down that path.

They may have dropped the MPSH on me, but even that bounces after it hits you…

The Million Pound Shit-Hammer

It is week 24 of the experimental trial; half down, half to go.

Current Condition:

Hair - Thin and White
Body - Thinner and White
White Cells - Thin but recovering
Red Cells - Thin but stabilizing.
Brain – Stabilized on Antidepressants

Which, as it turns out is a good thing as I got the news today that I had been dreading. The week 24 tests came back and the Hep C virus is Back.

They call it viral breakthrough (HCV-RNA falls with treatment, but then rises even though treatment is continuing). My latest viral load number is about 17,000 IU per ml.

This means that they will retest next week and if I am not undetectable in that test, they will stop my treatment under the experimental trial protocol. Needless to say, I am encouraging my body to kick it into gear over the next several days. I will have had two additional interferon doses since the original test was performed and I am holding myself optimistic that I will remain on treatment in the trial.

I have already emailed my gastroenterologist, the good Dr. C, asking him for his take on the efficacy of continuing on the Standard Of Care treatment of Pegasys and Ribavirin outside of the trial protocol and will ask the same question of Dr. B. the trial hepatologist when I am tested next week.

We’ll see how it all turns out, but I am definitely not giving up. Hep C is not going to win and I am going to keep fighting it until I clear it from my body.

I am still in shock about the news, so this will be short. I want to explore the implications more soon, but now I just want to watch mindless TV.

As an added note, Wednesday was my birthday. I’ll have to change my age to 57…