I know you have answered a lot of questions about mild anemia, but I am still having a little difficulty with 1. my doctors even discussing anemia, and 2. consistency in advise from various sources (NIH, NHHS, AMA, and Johns Hopkins as well as other sources).
History: 32 year male diagnosed in January 2003. Exercise 5 days a week. Initial viral load: 163,000 ; CD4 861; RBC 4.87; Hemoglobin 14.6; etc. In other words very healthy except for a high viral load. I began treatment taking Koletra and Combivir and viral load dropped to undetectable below 50 after about 3-4 months and CD4 climbed to 1106.
In the summer of 2003 I had what was I assumed to be a persistent illness for about a month or so. Symptoms were general ill feeling, tiredness, aching around the lymph nodes in my neck, mild grade fever (99 - 99.5), and shortness of breath. No congestion or tightness in the lungs. The general practitioner assumed it was a general upper respiratory illness, the HIV doctor assumed the same, chest x-ray was good, and treated it with some antibiotics for 2 weeks. After a month or so, I finally began to feel a little better. I didnt think much about it other than the exceptionally long time it took to get better. In the mean time, I continue to work out 5 times a week with little progress in muscle gain and with some weight loss. I increased protein through nutritional bars and tried to push myself harder working out. I did notice that I had a fair amount of difficulty concentrating directly following my workout until I had a chance to rest as compared to before taking medication.
In January of the next year, my HIV doctor decided to change me from Koletra to Reyataz as I had mentioned some stomach problems but nothing I couldnt handle. There was however some confusion and I ended up taking just the Reyataz and discontinued the Combivir. (Why someone would aggressively emphasize taking a medication only once a day as a selling point when you still have to take another medication twice a day I do not know, but that is another story.) After almost a month, I began to think that taking the Reyataz by itself didnt make any sense and called the doctor to confirm which is when we uncovered the mistake. He then decided to switch me from Combivir to Trizivir. No particular reason. I had not had any significant side effects from the Combivir that I had noticed. My viral load did climb to 83, but went back down to under 50 within in a month (I got lucky).
Around September of this year, I came down with another strange illness. I was very tired, general ill feeling, headaches, shortness of breath (completely out of breath after climbing one flight of stairs that I climb every day and I was still exercising 5 days a week), fast heart rate, difficulty concentrating, mild grade fever, and discomfort around the lymph nodes in my neck. No congestion in my chest and no nasal congestion or drainage of any kind. My general practitioner thought it was a bacterial infection, but wanted to check with my hot shot HIV doctor. The HIV doctor, without examining me, declared it to be an allergy and wrote it off even though I didnt have any symptoms of an allergy (further confirmed by the top allergist in the region who has excellent credentials including training at a top medical school and NIH). I confronted him with this second opinion regarding the allergy diagnosis which I knew had no merit and the arrogant, hot-shot HIV doctor stood by his diagnosis even though there was no evidence of an allergy showing up in my symptoms, basophils, eosinophils, or lymphocytes etc. which were all perfectly normal. Needless to say, I decided the so called hot shot was not particularly bright and was more interested in protecting his ego by not admitting a mistake than providing me with appropriate care. Mind you, this doctor is at a highly respected university so I assumed that he would be competent and up-to-date. That was a bad assumption on my part.
I decided to change doctors, but since the facility does not allow patients to select their own doctors and are not allowed to change to a different doctor within the same facility I requested my medical records to take somewhere else. (No, they were not an HMO or HMO facility, I have luckily have a PPO plan) It was then that I found out to my surprise, that my blood work for the past two years was coming back with Hemoglobin levels around 12 - 13, RBC around 3 and with specific notations of moderate to marked macrocytosis. At no point was I told about any of this, nor was the risk of anemia with theses medication ever discussed with me. Admittedly this is only mild anemia, but I should have been told especially considering my list of symptoms. The lymph nodes themselves had me a little concerned about possibly being early stages of lymphoma, but since my WBC has been steadily around 5.5 with a standard deviation of about 0.2 the whole time, I was able to calm my concern. During this time, I started eating out (junk food) more often instead of cooking for myself as I was too tired essentially doubling my calorie intake. Contrary to my expectations, I did not gain any weight from this. Not that I am particularly complaining about that, I just thought it was strange that I should be able to double my caloric intake with less physical activity and not gain weight.
I located another physician at another reasonably respected university and presented my records and described the history. She blew it off and said that nothing was wrong. I asked her to specifically tell me why she felt that the blood work results were irrelevant and she simply responded that I should let her worry about the numbers. I then pushed her and she said that the low hemoglobin numbers were simply normal variation. When I asked about the symptoms, she said not to worry about it, but she thought I should have the shortness of breath checked out (of course, she is a doctor and could have done that herself).
Interestingly enough there are a couple of variations in the numbers. In January of this year when I stopped taking the Combivir for a month, my hemoglobin whet up to 14.6, my RBC which had baselined at 4.9 went up from 2.9 on Combivir to 3.9, my MCV which had base lined at 89 and had steadily increased to 124 dropped to 106. Bilirubin levels had remained within normal ranges during the first year and serum albumin had remained very constantly around 4 - 4.5. All liver enzymes were within normal. At the same time in 2003 that I had the first extended illness, the hemoglobin was at it lowest level around 11.9 and the MCV was around 120. When I stared feeling better the hemoglobin climbed to 13. In addition, when I started having symptoms this past fall while on Tizivir, my hemoglobin had again dropped to 12, MCV had climbed to 120 again and this time the total bilirubin levels had increased to 2.1 from 0.7 and the serum albumin remained at 4.5.
Needless to say I need to find a doctor that will at least be willing to discuss hemoglobin levels and who will not attempt to give simply dismissive answers. If you make a diagnosis with me, I expect you to be able to describe the clinical facts that back-up that diagnosis especially when diagnostic test results are in hand. As you can tell, I have done a bit of my own research on the topic, but I have to say that there does seem to be a bit of question as to the time to begin treatment for mild anemia. The guidance documents from NHHS that I could find do not mention any treatment for hemoglobin levels above 7.5. NIH has some information on there site about the importance of treating mild anemia, but they only say below normal range with no more specifics. I have seen some studies that grouped men and women together and consider the normal hemoglobin range to be between 12 and 18 which probably explains why those particular studies showed a higher percentage of women than men meeting their threshold of inclusion in the mild anemia category. The drug companies in their physician guidance documents and studies presented the FDA use 7.5 as the threshold when they discuss anemia and thus do not discuss mild anemia at all, but they do have a market push/bias to play with the statistics and to use a lower threshold and give the appearance of fewer patients showing side effects.
I have taken it on my own to start taking B-12 supplements. This seems to be working. I have more energy, am not as fatigued, the discomfort around my lymph nodes has gone away, I am able to concentrate better, and generally feel much better. I can actually sit through a 9 hour meeting again without nodding off several times. I havent had a new set of blood work run since I began taking the B-12 supplement, but I suspect it will be interesting. Also, at no point has either doctor performed a check on my testosterone levels. I at least would have thought they would have wanted to take a baseline.
Am I just over examining and giving these doctors a hard time with this mild anemia thing when I look at the numbers myself especially considering the way the hemoglobin etc returned almost to baseline when I stopped the Combivir for a month and then went back down when I started the Trizvir with the most pronounced symptoms occurring at times when the hemoglobin level was down around 12? Note that I did not know at the time that the hemoglobin levels were low. I only discovered this after the fact? It seems almost like 13 appears to be the magic level where symptoms appear for me.
Are there solid guidelines about treating mild anemia? If not should there be?
What do you make of the increase in bilirubin levels in this last round while I was on Trizivir while the albumum levels remained normal? Is this typical with Trizivir? The numbers while on Combivir seemed to be consistent with mild anemia caused by Combivir and potentially treatable with B-12 and or folic acid, but the increased bilirubin suggests that some of the reduction in hemoglobin could be resulting from the red blood cells being destroyed and not simply malformed or perhaps not properly eliminated at the normal end of the cell life. I wasnt sure if this would be typical or if it might be an additional unrelated factor that I may need to look into further.
What is with this practice today of having a separate HIV doctor from regular internal medicine specialist? I dont know when I get sick if it is related to HIV or is just a regular illness and the regular internal medicine physician doesnt know enough about HIV to tell either. It would seems much more practical to have the HIV physician as the primary or at least have an internal medicine physician within the same practice for everyday problems. That way the close relationship between the two might make it easier to treat both issues.
Also, at no point has either doctor performed a check on my testosterone levels. I at least would have thought they would have wanted to take a baseline.
Let me try to address your major concerns:
In HIVers, anemia is associated with increased morbidity and mortality. In addition, it dramatically influences quality of life, particularly because of its contribution to fatigue. Regarding when and in whom to initiate treatment for anemia, in my opinion, the threshold for treatments depends on the purpose of therapy. By that I mean there is general consensus that lifesaving therapy, such as blood transfusion, is needed at extremely low hemoglobin levels. There is also considerable evidence that treatment of moderate anemia is associated with improved survival in HIVers. Finally, evidence is also accumulating that treatment of milder anemia is associated with improved quality of life. Consequently, I would consider treating anemia in patients with HIV infection when the hemoglobin level falls below 12 g/dL in men and 11 g/dL in women. Certainly clinical judgment, with the goal of maintaining quality of life and functional status, is a crucial component in this decision. I should also mention that initiation of therapy depends not only on the hemoglobin level, but also on the rate of decline and the presence of underlying diseases.
HIV medications, such as AZT, can deplete your red blood cell count and cause anemia by suppressing the production of red blood cells in bone marrow. AZT is a component of both Combivir and Trizivir. AZT also causes an increase in MCV.
Effective treatment of anemia depends on diagnosing the cause or causes and specifically treating the underlying condition. For example, anemia cause by nutritional deficiencies in iron, vitamin B12 and/or folic acid should be treated with supplements. Anemia caused by blood loss due to active bleeding is treated by stopping the blood loss. Anemia caused by HIV itself (anemia of chronic disease) or AZT-induced anemia can be treated with Procrit, a medication that stimulates the bone marrow to increase production of new red blood cells.
I agree all HIVers should be under the care of an HIV specialist. Unfortunately, because there aren't enough qualified specialists available for the ever burgeoning load of HIVers and because HIV medicine has become an increasingly complicated subspecialty, many HIV specialists do not have the capacity to be a primary care provider. However, I believe it's vitally important that you develop a healthcare team (primary care, HIV sub specialist, etc.) that meets your needs. Arrogance and not being willing to admit a mistake are certainly characteristics that would lead me quickly to find a more competent and compassionate provider to work with. Since you have a PPO plan, I would continue to search for an HIV specialist with whom you can develop a better relationship. Certified HIV specialists listed by locality can be found on the American Academy of HIV Medicine's Web site, www.aahivm.org. Once you've settled on an HIV specialist, ask him or her who they work well with on a primary care level and then see if any of those physicians is a good fit for you.
- There are many potential causes of fatigue in the setting of HIV disease. Certainly hypogonadism (low testosterone) is a very common one. Studies indicate between 25 and 45 percent of all male HIVers suffer from low testosterone. Yes, I agree you should definitely have a testosterone level checked and consider supplementation if your levels are confirmed to be low. For other potential causes of HIV-related fatigue, review the archives of this forum.
Finally, I addressed several points I felt were important in deciding on an HIV specialist in a recent posting. I'll reprint that below, as you may find it helpful.
Good luck, Michael.
Switching treatment: Question Posted: Dec 23, 2004
My HIV Doctor is a very well known and therefore I am somewhat hesitant to ask this question. He does not spend any time with me talking about diet or quality of life issues. Your forum has provided me with super info. on these subjects. He simply goes over my lab results, checks me out for less then 10 minuets and is gone. Here is the question. I have been positive for app. 5 years. My meds are Kaletra, Epivir, Zerit. I am experiencing some weight and fat loss but other then that, nothing big. My numbers are relativily good. Not undetectable, CD4 in the 400's. He wants to discontinue the Zerit and Epiver and start me on Epzicom. When I asked him about this he said it was for conveience and no other reason. Because of my concern for drug resistence, is this a good idea? And also, is this new drug the same as my old one? He gave me the option to continue with my old regimine. I have never had trouble adhering to my old regimine. It is now decision time. Please respond as soon as possible. Have a great day and thanks for the valuable info. you provide to us otherwise "ignorant" people.
Dr. Bob' Response:
Never ever be hesitant to ask a question! Just because your HIV doctor is "well known" doesn't necessarily mean he's either competent or compassionate. Doctor Seuss is well known, but I wouldn't let him take care of my HIV disease. That he "does not spend any time with me talking about diet or quality of life issues" already throws up a red flag in my book. Going over your lab results and doing a superficial 10-minute checkup may occasionally be sufficient, but if that's your regular routine, I'd say it's time for you not only to start asking questions, but also to start demanding more comprehensive care. You are experiencing weight loss and fat loss, and are considering a new regimen. These are far from trivial issues. Clearly your doctor's reply to your question about changing from Kaletra, Epivir and Zerit to Kaletra plus Epzicom was inadequate. Convenience is not really your issue since you "never had trouble adhering" to your old regimen. Let me start with the facts. Epzicom is not the same as Epivir plus Zerit. Epzicom is a combination of Epivir plus Abacavir. In essence, you'd be switching Zerit for Abacavir. It is true that Zerit has been implicated in the development of lipoatrophy (fat loss); however, prior to considering abacavir, you should understand that this drug also possesses significant toxicity risks, the most serious being a hypersensitivity reaction (similar to a severe allergic reaction) that can result in death. People taking abacavir need to be counseled on the signs and symptoms to watch out for, before beginning the drug. There are also a number of other switch options open to you that would address your concerns about lipoatrophy. Apparently these were not discussed with you. It is not merely a choice of your old regimen versus Kaletra plus Epzicom. It may be decision time, but at this point, I don't believe you've been given enough information on all the options available for you to make an informed decision. I'd suggest you ask your doctor for an extended visit (at least 30 minutes!) to discuss all treatment options, potential side effects and toxicities. If he is unwilling to cooperate, it's time for you to consider another decision. Is this the guy you want to work with? As persons living with HIV, we face enormous challenges keeping ourselves healthy. To optimally do so, we need to take a very active role in all our healthcare and treatment decisions. Part of "taking charge" of the situation is assembling a healthcare team that meets your personal standards for both treatment and care. One might assume finding a "well-known" doctor is all that's required, but in reality that is not enough. To increase our chances of keeping ourselves healthy as possible for as long as possible, we need to find the right doctor! Personally, I would suggest searching for an HIV specialist who:
- is indeed an HIV specialist (ample experience in treating HIV disease).
is a "hands-on" practitioner, not just a researcher.
keeps up to date on the latest treatments (and encourages you to do the same).
is open minded, willing to listen and follows your lead in terms of how actively you want to be involved and how aggressively you want to fight your illness.
is connected to a network of other HIV-knowledgeable specialists and is willing to consult with them or refer you to them when necessary.
will help you evaluate supplemental or complementary therapies and participate in clinical research trials if you so desire.
encourages you to ask any question on any issue at any time, and answers you in language you can understand.
is sensitive to your particular lifestyle concerns, is nonjudgmental and does not try to change you.
is sensitive to any addiction/abuse history you may have and will openly work with you on recovery-sensitive prescribing and lifestyle options.
has a reasonable patient load so that you are not always kept waiting for appointments and so that you don't feel rushed.
keeps your medical files confidential.
has a personality and "bedside manner" that puts you at ease and makes you feel secure.
has an optimistic attitude toward HIV infection.
is interested in you as a complete human being a real live person and not just a case or clinical problem.
understands "quality of life" issues and adds them into any treatment equation.
Your decision to swap abacavir for Zerit is not an urgent one, so perhaps you should first decide if your ongoing relationship with "Dr. Well-Known" should indeed be ongoing! I'd also suggest you review the information in our "Switching Treatment" forum.