HIV/AIDS Skepticism

Pointing to evidence that HIV is not the necessary and sufficient cause of AIDS

What do CD4 counts mean?

Posted by Henry Bauer on 2010/01/29

The level of CD4 cells in peripheral blood is a prime criterion for diagnosing AIDS (in the United States in particular) and for monitoring antiretroviral treatment. However, these applications of CD4 counts stem from the initial and unhappy coincidence that when “AIDS” appeared around 1980, the counting of immune-system cells was in its infancy. By now it is known that CD4 levels are extremely variable in healthy individuals, and that a variety of physiological conditions other than “HIV” may profoundly influence CD4 counts. There seems to be no fundamental evidential warrant for the manner in which HIV/AIDS diagnosis and treatment rely on CD4 counts. Juliane Sacher among others has pointed out that the levels of CD4 cells in peripheral blood are not a meaningful measure of immune-system status, since these cells move around the body according to where they seem to be needed [Alternative treatments for AIDS, 25 February 2008].

An obvious question: what is the range of CD4 counts in healthy individuals and in a variety of illnesses? (I’m grateful to Tony Lance for alerting me to some of the intriguing sources mentioned in the following).

One of the striking aspects of CD4 counts is how enormously they vary among individuals, including healthy individuals. Here, for example, are data from HIV-negative Senegalese:

C. Mair, S. E. Hawes, H. D. Agne, P. S. Sow, I. N’doye, L. E. Manhart, P. L. Fu, G. S. Gottlieb and N. B. Kiviat. Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals. Clinical and Experimental Immunology 151 (2007) 432-440

In any normal distribution, the standard deviation (s.d. or σ) describes the degree of scatter around the average (or mean) value. Only about 2/3 of a sample are within (±) 1 σ; in other words, about 1/6 are further from the mean on both the higher and the lower sides. In the Table above, among the men with mean CD4 count of 712, σ = 333, about 1 in every 6 men have CD4 counts below 379 or above 1045; and about 2% have counts more than 2σ above and below 712 , that is >1378) and <50. CD4 = 200 is about 1.5σ below the mean, which corresponds to about 6-7% (~1/15) of the sample. In other words, about 1 in every 15 healthy HIV-negative Senegalese men has CD4 counts below the 200 that, in HIV-positive people, is taken to be a sign of AIDS.

Of course, CD4 counts may not follow a normal distribution, especially at upper and lower levels; but since this article reports means and standard deviations without specifying a different distribution, the authors themselves are presuming it is normal. Moreover, a similarly wide range of CD4 counts and an approximation to normal distribution is shown in other data sets as well. For example, healthy North Indians were reported to have a mean CD4 count of 720 with σ = 273 and an actually observed range of 304-1864 among 200 individuals; 10% were below 400, consistent with a normal distribution which would have about 16% below 450 (Ritu Amatya, Madhu Vajpayee, Shweta Kaushik, Sunita Kanswal, R.M. Pandey, and Pradeep Seth. “Lymphocyte immunophenotype reference ranges in healthy Indian adults: implications for management of HIV/AIDS in India”. Clinical Immunology 112 [2004] 290-5). Actual distributions for several African populations, however, show a skewing toward higher CD4 counts, which indeed seems highly plausible a priori — one might expect to see a definite lower bound to CD4 counts in healthy individuals (Williams et al., “HIV infection, antiretroviral therapy, and CD4+ cell count distributions in African populations”, J Inf. Dis. 194 [2006] 1450-8).

Worth particular note is the comment in Amatya et al. that “These low counts could be due to physiological lymphopenia potentially caused by protein energy malnutrition, aging, antigenic polymorphism of the CD4 molecule, prolonged sun exposure, circadian rhythm, and circannual variation [9,10]”. The use of contraceptive pills by women has also been reported to influence CD4 counts (M. K. Maini, R. J. Gilson, N. Chavda, S. Gill, A. Fakoya, E. J. Ross, A. N. Phillips and I. V. Weller. “Reference ranges and sources of variability of CD4 counts in HIV-seronegative women and men”. Genitourin Med 72 [1996) 27-31]. Most of those circumstances do not represent illness. So CD4 counts can be low for a variety of fairly normal, not seriously health-threatening conditions. It follows that reliance on CD4 counts as diagnostic of “HIV disease” increases the danger that some unknown number of “HIV-positive” individuals are being told on the basis of laboratory tests — sometimes SOLELY on the basis of laboratory tests — that they are actually sick even though they feel and actually are healthy; and these people are then at risk of being consigned to toxic “treatment” for this imaginary illness. The risk is greatest if the blood tested for CD4 counts happens to have been drawn in the morning, or in the wrong season of the year, because CD4 counts vary appreciably with both those variables: T. G. Pagleironi et al., “Circannual variation in lymphocyte subsets, revisited”, Transfusion 34 [1994] 512-6; F. Hulstaert et al., “Age-related changes in human blood lymphocyte subpopulations”, Clin. Immunol. Immunopathol. 70 [1994] 152-8. Maini et al. (above) report a 60% variation during the day with lowest counts at 11 am. Yet another report describes a similarly large diurnal variation, from 820 at 8 am to 1320 at 10 pm (Bofill et al., “Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis”, Clin. Exp. Immunol. 88 [1992] 243-52).

Just as with the tendency to test “HIV-positive”, CD4 counts are influenced by demographic variables: “race, ethnic origin, age group, and gender” (Amatya et al.). Bofill et al. also report a steadily decreasing CD4 count with increasing age. The contrary has been reported, however, by Jiang et al. (“Normal values for CD4 and CD8 lymphocyte subsets in healthy Chinese adults from Shanghai”, Clinical and Diagnostic Laboratory Immunology, 11 [2004] 811-3). The discrepancy may be owing to differing attitudes toward statistical significance: the raw numbers in Jiang et al. do show an increase with age for men and a decrease with age for women but, as with the data of Bofill et al. and all others, the standard deviations are so large, on the order of one third of the mean values, that differences and trends would have to be very considerable if they are to be statistically meaningful.

Again, Jiang et al. report no difference between Chinese men and women, whereas several sources cite women as having higher CD4 counts than men: in Britain (Maini et al.) and in more than dozen other countries in Africa, Asia, and Europe (Mair et al.). Caucasians have higher CD4 counts than Asians or Africans, according to Amatya et al. and Jiang et al., but not according to Maini et al.

All these variations under the influence of several factors would make the diagnostic application of CD4 counts problematic even if “HIV” or “AIDS” had been shown to be the salient influence on CD4 levels. However, just as with the tendency to test “HIV-positive”, CD4 counts may be “low” in a wide range of conditions; perhaps most relevant to HIV/AIDS, in tuberculosis and general trauma, as well as with primary immunodeficiency, early acute phases of such viral infections as influenza, or Dengue fever (Bofill et al.) or recent respiratory infections (Maini et al.).

Not only are CD4 counts dubious for diagnosis or prognosis; just as with the tendency to test “HIV-positive”, CD4 counts generate a number of conundrums if interpreted according to HIV/AIDS theory: the counts are often HIGHER rather than lower in conditions generally regarded as associated with poor health. For example, smokers have higher CD4 counts than non-smokers (Maini et al., Mair et al.) and prostitutes have higher counts than other women (Mair et al.). Another “striking paradox” is in “co-infection” with “HIV” and herpes:
“We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naïve, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear” (emphases added; Barbour et al., “HIV-1/HSV-2 co-infected adults in early HIV-1 infection have elevated CD4+ T-Cell counts”, PLoS ONE 2(10) [2007] e1080).

************************

There seems to be no clear warrant for diagnosing AIDS by means of CD4 counts, which may be why other countries have not followed the US example of taking <200 as a criterion. Similarly, there seems to be no clear warrant for assessing the progress of antiretroviral treatment by means of CD4 counts. Two practical illustrations of that are the fact that CD4 counts do not correlate with (or, changes in are not predicted by)  “viral load” (Rodriguez et al., JAMA, 296 [2006] 1498-1506), and that the NIH Treatment Guidelines distinguish immunologic failure (no increase in CD4 counts) from virologic failure (no decrease in viral load) and from clinical progression (does the patient’s health improve?).

A somewhat related illustration of the failure of HIV/AIDS theory is that “AIDS” patients with Kaposi’s sarcoma may have quite high CD4 counts: see for example Maurer T, Ponte M, Leslie K. “HIV-Associated Kaposi’s Sarcoma with a High CD4 Count and a Low Viral Load”. N Engl J Med 357 (2007) 1352-3; Krown SE, Lee JY, Dittmer DP, AIDS Malignancy Consortium. “More on HIV-Associated Kaposi’s Sarcoma” N Engl J Med 358 (2008) 535-6; D.G. Power, P. J. Mulholland K. J. O’Byrne. “AIDS-related Kaposi’s Sarcoma in a Patient with a Normal CD4 Count”. Clinical Oncology 20 (2008) 97; Stebbing J, Powles T, Bower M. AIDS-associated Kaposi’s sarcoma associated with a low viral load and a high CD4 cell count. AIDS 22 (2008) 551-2. Mani, D., Neil, N., Israel, R., Aboulafia, D. M. “A retrospective analysis of AIDS-associated Kaposi’s Sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells/mm3”. J Int Assoc Physicians AIDS Care (Chic Ill) 8 (2009) 279-85.

But then it has also long been known that “AIDS” Kaposi’s sarcoma is not caused by HIV, it’s now attributed to KSHV or HHV-8, which just happened — by the sort of extraordinary coincidence or oddity that is so common in HIV/AIDS matters — just happened to appear at the same time among the same risk groups as “AIDS” and “HIV” did; and then just as mysteriously went a separate path, so that KS declined from about 40% of all “AIDS” case in 1982 to well under 10% from 1987 onwards (Table 30, p. 128 in The Origin, Persistence and Failings of HIV/AIDS Theory).

More sales in the offing for snake oil and Brooklyn Bridges.

19 Responses to “What do CD4 counts mean?”

  1. I believe the statistical discussion is correct but a bit confusing because it talks about both the high and low end of the putative normal distribution when we’re interested in only the low end. For example, it’s not clear whether, “about 1 in every 6 men have CD4 counts below 379 or above 1045” means that 1 in 12 are above and 1 in 12 below (adding up to 1 in 6) or 1 in 6 are below 379 and similar 1 in 6 above 1045.

    To be absolutely precise, the difference between 1 and 2 standard deviation is 13.6% on the low side (and the same on the high side). And 2.1% are expected between 2 and 3 SDs on the low side (and also on the high side). Source: Wikipedia (ha ha).

    For the expected percentage of counts 1 or more SDs lower than the mean we can use 15.9% (a bit lower than the 1/6th used above) and the expected number of values 2 or more SDs lower than the mean is 2.3%.

  2. In the Mair study a more complete list of CD4 factors is:

    Factors associated with lower CD4 counts than average are 1) age below 20 or over 30]; 2) young age at first intercourse (≤15); 3) old age at first intercourse (≥19); 4) Fever; 5) high blood pressure; 6) cough; 7) diarrhea; 8) weight loss; 9) pneumonia; 10) swollen lymph nodes; 11) oral leucoplacia; 12) more than 8 children; 13) use of oral contraceptives; 14) abnormal discharge; 15) cervicitis; 16) pregnancy; 17) TB; 18) tallness; 19) maleness

    Factors associated with higher CD4 counts than average are 1) Alcohol use (add 67); 2) Current tobacco use (add 115.6); 3 low weight (60kg);5) Shortness; 6) more schooling; 7) marriage; 8) commercial sex work; 9) birth in Senegal

    So, my advice to people is. Find the inner woman in you. Get married (but not polygamously). Smoke, Drink. Go on a yo-yo diet. Go to school. Be a prostitute. Don’t get sick. And you’ll be fine.

  3. Joe said

    Hi Henry, just to say that I have gay friends in the UK who within the last 2 years were diagnosed as having AIDS, and being put on ARVs because their CD4 count fell below 200. These friends had no actual signs of illness to indicate an AIDS diagnosis.

    Maybe the important diagnostic factors are a) cd4 count, b) being gay or black or a drug user.

    • Henry Bauer said

      Joe: Were their CD4 counts taken (blood for them drawn) just once, or several times, at different times of day? Do their physicians know about the secular variation?

      • Philip said

        Even if the physicians had known, I doubt if they would have given it much pondering. I admit that for physicians like myself sometimes you just look at the paper and that’s that. You don’t really *ask* “what time was this taken” etc etc.

      • onecleverkid said

        One thing Joe is pointing out, and this whole blog post doesn’t seem to touch on, is the idea that it is when CD4 cell numbers drop and drop and drop, in what seems like a steady decline. This is usually the factor that leads to the advice to start the drug regimen (from what I’ve been told by several people in that position). So, it still seems unanswered: Are steadily declining CD4 numbers a predictor of illness? This fascination with the number itself seems useless, but perhaps declining or rising numbers do have some predictive value?

      • Joe said

        Henry, I don’t know what the doctors know. I was just pointing out that the CD4 < 200 seems to still be used as an indication of AIDS and as trigger to initiate ARV treatment.

        My friend who challenged the AIDS doctors most found the doctors seem unaware of any complicating factors in making their judgements. So I doubt that they have any idea that there might be significant variations in count depending on time of day. It doesn't seem to have impinged on their consciousness that even though they are in an almost entirely Asian area, their HIV/AIDS patients fall into three groups: gay, drug users, or African.

        Sometimes my friends on ARVs relate to me the reactions from the nurses when they have their regular blood analysis done. Depending on the nurse a different event will be highlighted each time: "your cholesterol is high" one month, or "your calcium levels are low" the next month. No explanation is given concerning why this might be significant, what might have caused it, what should be done to correct it. I think most of my friends take away from all of this that as long as their CD4 count is increasing, and the "viral load" is decreasing then they are OK.

        During these routine events the patients do not hear from a doctor. Until they become seriously ill they will not see an AIDS doctor again.

      • Henry Bauer said

        Joe: You’re really confirming my speculation, that AIDS treatment is done “by the numbers” and by routine. Yet Weiss & Cowan make abundantly clear that even diagnosing “HIV infection” can’t be done by the numbers, and the NIH Treatment Guidelines make amply clear that antiretroviral treatment must include constant informed monitoring — see Grabbing a monster by the tail.

        .

      • Philip said

        not necessarily by “routine” per se. Medical practice today is dominated by sticking to “protocols” and “treatment guidelines”. You try something different and you can get scolded for it. Thus, what starts out as a “guideline” becomes a blind, robotic, svengali like slavery.

  4. Safely quitting HAART medication is now a concern of mine. Since my friends, including some on anti-retroviral medication, are becoming more aware of my HIV skepticism, some are consulting with me about how to quit safely. Has HEAL or other such organization prepared a pamphlet or a web site for such people? Is there a Patients Like Me group to discuss the problems which may arise and what works to handle them?

    • dog said

      Richard Karpinski

      One of the most prominent individuals I know who has taken the step to quit her antiretroviral therapy is Karri Stokley. She has a website at http://www.myspace.com/rethinkaids and another at https://sites.google.com/site/karristokely/home.

      She has given several interviews and speaks openly about her undertaking. Particularly noteworthy is the observation that some ARVs appear to have narcotic properties (also noted by Clark Baker). This is particularly important because quitting ARVs may result in the onset of withdrawal symptoms. This undertaking therefore requires some serious thought as to what to expect, up to and including sticking with your current therapy.

      Karri does not presume to give medical advice (read her disclaimer), and neither am I. She may be more likely than most of us to answer questions you might have, or point you in directions that worked for her.

      • Dog,

        Thanks for the links. Karri is brave and has built two rich sites to explore. I knew about Sustiva and wonder if anything can be done to alleviate the withdrawal symptoms. Adding an addictive component to HAART seems needlessly cruel, but cruelty is not new for either AIDS or the LGBT community.

      • Aha! This is exactly the site I was seeking: http://www.livingwithouthivdrugs.com/ so now I know a great place to send anyone who is thinking of stopping or even avoiding taking dangerous drugs for conditions which may not mean anything important. Thanks for your help in finding it.

  5. Cal Crilly said

    CD4 counts are from opposite world, if you have low T-cell counts it probably means you are perfectly well and not reacting to infections or allergies… if you have really high T-cell counts it really means you’re immune system is probably attacking an infection, there are allergies or you’re immune system is ripping your body apart.
    I now think low T-cells indicate less drama.
    The reason T-cells rise when taking AIDS drugs is simply because they are poisonous so the immune system is reacting to the poisons.

    • arkadi renko said

      Dear Cal
      Do you mean to say that the less lymphocytes you have, the more healthy you are? Should I be happy about the fact that my lymphocyte count keeps falling and consider it as a strenghtening of my immune system?,

  6. I stopped Truvada & Raltegravir in Sept. 2013. A rebound effect was not unexpected. Nov/Dec. is ALWAYS an emotionally low time for me. I went through a few months of malaise, inability to put on weight (UNUSUAL) and dyspepsia. I had 3 gallstones taken out when I was hospitalised for 5 months from Christmas Eve 2010. At that time I had a multitude of “REAL,” diseases:
    (disseminated MACm CVM colitis + retinal, D. dif., PCP -bronchial lavage was performed and substance with the consistency of “crushed ping-pong balls was cultured, two “undiagnosable parasites -one in my gut & one in my blood). All these diseases were well earned via a lifetime of emotional stress and risky behaviour. -I’m 54 now.

    I take excellent care of myself. Enjoy organic cooking, avoid restaurants and the stressors have been removed for quite a while. I have inflammation (low iron + a ferritin level over 2000). Doctor will investigate lupus & rheumatoid arthritis. I am sure a lot of this is emotional or damage done by the multitude of meds that were required to save me in 2010/11 once “I DECIDED,” to stay on the earth and allow treatment. There is no blame.

    As of yesterday, “IF,” one subscribes to “Medicine by numbers,” I’m dead even though I feel fine & am strong & can put on weight at will. The HIV #’s are in the millions and there are less than 20 CD-4 cells.

    I get a mild fever about every three or four months (under 40c.) which lasts a few hours. Occasionally I spray “mud.” I’ve had migraines & gut issues since I was born and they are OCCASIONAL and not unrelated to bright light, emotions & gallbladder. No swollen glands, no night sweats. All “healthy,” people I know have had colds and flu …I’ve been around them …I NEVER GET SICK.

    CMV & MAC are monitored but not treated prophylactically. There is a certain amount of antimicrobial activity provided by the Truvada & Raltegravir regime …fortunately, when I took it I felt no side effects other than I had more energy. It is my intention to remain free of ARV’s, at the same time …not allowing pride to prevent me from using them “IF” I so choose.

    Apathy is my biggest issue …but as so many of you in my age group …having lost ALL one’s friends several times over …it can be a challenge to muster motivation.

    I have followed R/A and Joan Shenton’s Immunity Resource for a long time and they must also be thanked for their tireless work.

    Thanks for this site. If my CD-4 count had actually come up I wouldn’t have found it. It makes more sense, to quote Mike Hersee from HEAL London, “My T-cells are busy going about the business of keeping me healthy.”

    • Rogers said

      For how long have you been positive and for how lond did you use the meds?

      • Probably 20 years. Tested against my better judgement -because of romance in 2005.

        dYou can read my entire, lengthy story at Questioning AIDS under: “Kewlaid” (as in “Drink The…”

        I had a laundry list of life threatening diseases all at once. I took the Truvada & Raltegravir for 1.5 – 2. years after I was out of the hospital in 2011 + a laundry list totally 19, of other debilitating meds:
        Cipro & Ethambutol were the harshest. Bactrim a close second. I worked on cruise ships for 20 years. VERY VERY STRESSFUL. Crew/entertainers are always coming down with bronchitises and the doctors hand out sulfa antibiotics like candy …drugg’em and keep em performing.

        Right now I feel great. Energy swings balanced out. Dr. appt. tomorrow. I take Dexedrine, Xanax, morphine & have found an abstract from the American Journal of Virology talking about the effects of Alprazolam vs. Valium on immune suppression. It’s too complicated for me. Will take it to my Dr.

        We know not to do “Medicine by Numbers.” I’ve never taken Xanax on a regular basis on land when I was also taking amphetamine. I did so on ships because they want you to sleep and maintain a regular schedule …but that was finite periods of time …i.e. 4 – 6 months. The exception was went I moved to B. Hills in ’89 & was taking .25 mg Xanax 6 times a day …but wasn’t using stimulant during that time.

        What I take is my choice. So I’m going to explore cutting back the Xanax. Interesting that I’m far more terrified of stopping Xanax than I am of possibly dying tomorrow. Curiouser and Curiouser said Alice

  7. Benedetto said

    what about the cd4/cd8 ratio? talking wih a positive friend of mine, he said that, at least here in Italy, doctors rely moslty on this other marker. maybe this is more reliable in assessing the progression to aids?

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