Acquired Immune Deficiency Syndrome (AIDS) may Actually be HIV-Induced Dehydroepiandrosterone (DHEA) Deficiency Syndrome
(A Response to Journal of Acquired Immune Deficiency Syndromes 2003; 33: 635-641)
Copyright 2003, James Michael Howard, Fayetteville, Arkansas, U.S.A.
In 1985, I first suggested that a "reduced level of DHEA is responsible for AIDS." The first reports of reduced DHEA in AIDS appeared in the literature in 1989. I have continued to study this connection of reduced DHEA and AIDS since 1985. However, this is a response to data reported in a new report that allows me to better demonstrate that "acquired immune deficiency syndrome" may actually be "HIV-Induced DHEA deficiency syndrome."
It is my hypothesis that DHEA was selected by evolution because it may "optimize" replication and transcription of DNA. Therefore, DHEA should positively affect all tissues, some tissues more than others. I decided that the immune system was one of these tissues. As DHEA declines during AIDS, all tissues would be adversely affected, hence, I decided that the decline of AIDS is due to the decline of DHEA. That is, the symptoms of AIDS are symptoms of loss of DHEA. Since I also think that the decline of old age is due to the natural reduction of DHEA, I suggest AIDS is a form of premature aging.
I have not written about my hypothesis regarding DHEA and AIDS in some time; I have been pursuing other functions of DHEA. Much information has been published regarding a possible connection of DHEA and AIDS since my last attention to this connection. It is my contention that testosterone reduces availability of DHEA and, therefore, testosterone increases the effects of AIDS. It is known that males and blacks exhibit more negative effects from AIDS. Males and blacks produce more testosterone.
This treatise is an attempt to reconcile levels of DHEA and testosterone with CD4+ and CD8+ levels in HIV infection. JAIDS 2003; 33: 635-641 provides a set of data which may support a connection of DHEA with HIV infection. HIV alters the ratios of CD4+ and CD8+ and reduces DHEA, therefore increasing the testosterone to DHEA ratio. I suggest increasing this ratio may be shown to affect the ratio of CD4+ and CD8+ alone.
Here is the abstract of JAIDS 2003; 33: 635-641 produced by the "European Collaborative Study," (ECS). I contend that the data within this article demonstrates a connection of DHEA and testosterone levels with levels of CD4+ and CD8+ lymphocytes in uninfected and HIV infected children.
"This study investigated whether age-related patterns of immunologic markers in 1488 uninfected (9789 measurements) and 186 infected (3414 measurements) children differed by gender and race. CD4+, CD8+, and absolute lymphocytes by HIV infection status, gender, and race were assessed using linear mixed-effects natural cubic spline models, allowing for prematurity and maternal CD4+ cell count. In uninfected children, levels of all 3 markers peaked twice in the first few months of life, declining to adult levels by around 8 years of age; uninfected boys and uninfected black children had significantly reduced CD4+ and absolute lymphocyte counts; the gender difference was especially pronounced in black children. Infected children had substantially lower levels and distinctly different patterns; with, e.g., by age 6 months CD4+ cell counts nearly 1200 per mm3 lower than in uninfected infants. Levels also significantly differed by gender and race for infected children, although for gender in the opposite direction. The gender and race differences in CD4+ levels were not explained by a general lymphocytosis nor were they confounded by treatment. These substantial differences in immunologic markers may reflect underlying genetic influence on the cellular immune system and may have implications for clinical decisions about therapeutic management."
To demonstrate the connection of DHEA and testosterone levels with these lymphocytes, I will show chronological correspondence of levels of the hormones with levels of lymphocytes. (The following chart is derived from a combination of data in Adrenal Androgens, A.R. Genazzani, Raven Press, 1980.)
Period A is the first year; B is from one year to adrenarche; C is childhood; D is the reproductive period; E and F are redundancy, with E being reproductive redundancy and F, fatal redundancy.
"…a testosterone surge with peak values in the normal range of male adults occurs in healthy male infants during the first 6 months and elevated estradiol concentrations comparable to levels seen during advanced puberty can be observed in healthy female infants during the first 2 years of life." (Fortschr Med. 1980; 98: 235-8)
"Boys older than 3 weeks had higher values [of testosterone] than boys younger than 2 weeks." (Acta Endocrinol (Copenh). 1976; 82: 842-50)
In boys, testosterone peaks around three weeks, declines around six months, then increases again near puberty. For sake of the following interpretation, assume the hypotheses that DHEA stimulates CD4+ and whole lymphocyte count while testosterone reduces the effects of DHEA. When testosterone reduces DHEA availability, this reduces CD4+ count, but not CD8+ count. This may indicate that CD8+ cells response to lower levels of DHEA and may explain why the ratio of CD8+ to CD4+ increases in people with HIV disease. According to my explanation of AIDS, the HIV reduces DHEA so the effects of HIV infection and testosterone should be additive.
ECS reports the following findings in Uninfected Children.
"CD4+ cell counts peaked at 3 weeks of age, then dipped before peaking again at 6 months and declining gradually thereafter. The pattern for CD8+ cell counts was similar although with a more protracted second peak, while for the absolute lymphocytes both peaks were smoothed out." Page 636.
At birth DHEA is very high, declines rapidly the first year, then begins a large increase around age five to six years (adrenarche). I suggest this large level of DHEA stimulates CD4+ cells. It peaks around 3 weeks of age and then declines because of the increase in testosterone. That is, the onset of testosterone around 3 weeks begins a decline in the CD4+s. When the "testosterone surge" declines around six months of age, there is a momentary increase in CD4+s as the testosterone ebbs. DHEA at this time is beginning to decline so this momentary increase is not maintained.
"CD4+ cell counts approach adult values some time after age 6 years. For instance, the predicted CD4+ cell counts peak at 3238 per mm3 at 3 weeks, then again at 3009 at 6 months, dropping to 2597 at 1 year of age and to 1096 by age 5. For CD8+ cell counts, the predicted values peak at 1343 per mm3 at 2 weeks and then at 11 months at 1219; the subsequent … The predicted absolute lymphocyte values peak at 6470 per mm3 at 3 weeks, again at 6702 at 7 months; there was a subsequent gradual decline to 6149 at 1 year, falling to 3016 by 5 years." Page 636.
"CD4+ cells as a percentage of absolute lymphocyte counts fell rapidly from around 55% at birth, leveling off to just <40% by 2 years of age, asymptoting thereafter." Pages 636-7.
Here, again, one may suggest the same explanation as above. Additionally, one should notice that the CD4+ cell count and absolute lymphocyte follow the same pattern and increase again when DHEA begins to increase around 5-6 years (adrenarche).
"Contrary to what was seen for CD4+ cell counts, estimated levels of CD8+ cell counts did not vary by gender, although levels of absolute lymphocytes did. The direction of the association with race and gender was similar to that seen for CD4+ cell counts, with levels for white children higher than those for black children for both CD8+ and absolute lymphocyte counts. Predicted CD4% was higher for girls and white children, indicating that the gender and race differences seen in CD4 cell counts were not due to a general increase in absolute lymphocytes." Page 637.
Testosterone levels are higher in black people. Since the pattern of lymphocyte production in these data fit by gender in these children and my hypothesis regarding the effects of testosterone, I will assume that testosterone is also higher in black children. Accordingly, gender did not affect CD8+ counts but did reduce absolute lymphocytes. Girls and white children produce less testosterone.
ECS reports the following findings in Infected Children.
Remember, from above, that I think the effects of HIV and testosterone should be additive.
"Observed CD4+ cell counts fell quickly below CD8+ cell counts before recovering slightly at around 8 years of age. …Similar to predictions for uninfected children, the peak of 1723 per mm3 for the predicted level of CD8+ occurs at 4 months, falling to 1639 at 1 year, reaching a nadir of 719 at just after 8 years." Page 637.
"The peak for absolute lymphocytes occurs at 2 months at 6738 per mm3, declining to 5098 at 1 year and falling to the lowest value of 1718 at 8.6 years." "Similar to the models for uninfected children CD4+ cell levels for white children are generally higher than those for black children, and both these and gender differences persisted after adjustment by antiretroviral treatment. The patterns by gender did not vary according to race." Page 638.
One may see the additive effects of HIV and testosterone in the data above.