AIDS & Dehydroepiandrosterone

Copyright ã 1995, 1996, 2014, 2015. Revised from 1985 James Michael Howard, Fayetteville, Arkansas, U.S.A.

Very Significant Support found July 18, 2014: RED material below chart “DHEA in Heterosexual and Homosexual Men,” third chart below. The last author, JM Lange was killed in Malaysian Airlines MH17 airliner shot down over the Ukraine, July 17, 2014. He was the main individual mentioned in news coverage of this event among the nearly 100 researchers onboard the plane headed to the International Conference on AIDS in Australia. I researched his work and found the report regarding DHEA and seroconversion in HIV infection which directly supports my hypotheses regarding same, below.

My explanation of acquired immune deficiency syndrome (AIDS) is derived directly from my foundation hypothesis that DHEA (dehydroepiandrosterone) is necessary for duplication and transcription of DNA . Since all tissues depend on DNA, I suggest all tissues depend on DHEA. Therefore, it follows that all tissues compete for a limited supply of DHEA. In 1985, I copyrighted the idea that low DHEA increases vulnerability to infection by the human immunodeficiency virus (HIV) and AIDS. In 1989, it was reported that DHEA is low in men infected with the HIV and lower in those with AIDS compared to healthy seronegative (virus free) controls (Journal of the American Medical Association 1989; 261: 1149). The key to understanding HIV infection and AIDS is that the immune system cannot capture enough DHEA to mount a satisfactory response to the HIV. I am convinced that treatment with DHEA may be the cure. I suggest the symptoms of AIDS are actually symptoms of severe loss of DHEA.

Another non-AIDS study reported that CD4+ lymphocytes declined and a form of CD8+ lymphocytes increased upon use of micronized DHEA (Am. J. Ob Gyn. 1993; 169: 1536). That is, large increases in DHEA in the blood reduce the total number of CD4+ lymphocytes and increase the total number of CD8+s. This pattern of changes in lymphocytes is considered typical of HIV infection. For example, one study found this pattern in HIV infection and also in "infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients" (AIDS 1995; 9: 561). (Remember that DHEA was not low in seronegative (non-infected, healthy) individuals in the JAMA study above.) Another study found differences in a different subset of CD8+ lymphocytes as well as reductions in CD4+ (AIDS 1995; 9: 421). In fact, the clinical features of infections by Epstein-Barr virus or cytomegalovirus resemble HIV infection, and specific antibody tests and history (clinical suspicion) are often necessary to distinguish these viral infections from each other (AIDS 1995; 9: 562). Also in the same journal: "The significance of the cytotoxic [subset of CD8+s] T-cell response in primary HIV infection is not known. However, increased CD8+CD38+ cells are associated with more rapid HIV disease progression and increased CD8+CD38- cells with stable CD4+ lymphocyte counts over time" (AIDS 1995; 9: 562). The important characteristic is that total CD4+s decline and total CD8+s increase in response to viral infections and increases in DHEA. I suggest the common link in total lymphocyte response and clinical symptoms is DHEA response. I suggest the differences in lymphocyte responses rest on the kind of virus and the individual's ability to respond with DHEA. Since the HIV kills CD4+ lymphocytes and increased DHEA also reduces CD4+s, the CD4+ decline is exaggerated during HIV disease and AIDS. This excessive reduction in CD4+s, above the expected CD4+ kill rate caused by the HIV, was noticed in 1988, but was not explained. The combination of HIV and DHEA on CD4+s is the reason. ("Micronized" DHEA is no longer considered to be a necessary form of DHEA for use.)


"Thus, it has been hypothesized that in addition to a direct HIV-induced cytopathic effect on a given T4 [CD4] cell, other potential mechanisms of T4 depletion may be operable." (Science 1988; 239: 619)

I suggest DHEA naturally increases in response to viral and bacterial infections in order to increase availability of DHEA for the immune system. The initial increase is probably derived from DHEA sulfate (DHEAS) in the blood: "DHA [DHEA] never reached zero concentration in plasma, whereas cortisol did. This is explained by the contribution to DHA by hydrolysis of the relatively abundant circulating DHA sulfate [DHEAS]. Because of the low plasma concentration a high degree of biological activity can be implied for DHA, the function of which is at present unknown" (J. Clinical Endocrinology 1971; 33: 87). Those who progress to AIDS, however, cannot maintain the DHEA response. In one study of AIDS, DHEA increased early during HIV disease, but all participants who progressed to full-blown AIDS had low levels of DHEAS (J. Acquired Immune Deficiency Syndromes 1992; 5: 841). They could not maintain their DHEA response to HIV, because they did not have enough DHEAS. (JAIDS is now called the Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. Do not confuse this journal with the one called AIDS.)


"At entry, DHEA levels were higher in the seronegative [virus free] group than in either the seropositive nonprogressors or the progressors. DHEA levels in the progressors approximately 5 months before the diagnosis of AIDS were lower than the levels in the nonprogressors after the same follow-up." (J. Infectious Disease 1992; 165: 413)

The importance of DHEA to the immune system in other mammals (e.g., mice) has been demonstrated.


". . .DHEA protects mice against West Nile virus, Sindbis virus neurovirulent, and Semliki Forest virus lethal infection. Though the mechanism of the protective effect of DHEA is still unknown, it seems that DHEA can modify the host resistance mechanisms rather than the virus itself." (Archives of Virology 1991; 120: 263)

At this point, I want to explain some basics of my theory in order to show how the AIDS research cited later in this paragraph supports my explanation. In proper context, it will be easier to see the connection. It is part of my theory of human evolution that the natural adrenal glucocorticoid hormone, cortisol, evolved to counteract the actions of DHEA, the major adrenal hormone. I think DHEA activates the nervous system; it is known that cortisol is produced during stress. Stress usually weakens our will to act on an impulse. I suggest this is the physiological basis of the "fight or flight mechanism." A person with high DHEA would have more motivation to confront an adversary. If a confrontation causes too much cortisol production, the motivation is weakened. Both of these hormones are produced by the adrenal gland; the gland stimulated in the fight or flight response. DHEA is utilized from the molecular level to the behavioral level, therefore, cortisol also affects DHEA function in the immune system. Cortisol should act in an opposite direction to that of DHEA on CD4+ cells. Remember that increased DHEA causes CD4+s to decline, along with the decline caused by the HIV. (Synthetic glucocorticoid hormones are used instead of cortisol in medical practice, because their structures increase their effects.) These hormones inhibit the decline in CD4+s that occurs during AIDS (AIDS 1995; 9: 35). I interpret this to mean that these glucocorticoids, like cortisol, inhibit the natural function of DHEA. While glucocorticoids may reduce the decline of CD4+s in AIDS and appear beneficial, use of glucocorticoids is known to have negative effects on the immune system when given over prolonged periods. When used too long, they interfere with the natural function of these cells caused by DHEA.


"The conclusion is that DHEA acts acutely as an antiglucocorticoid and exerts its effect in different glucocorticoid-sensitive systems." (American J. Medical Sciences 1992; 303: 366)

November 24, 1995, the Associated Press reported the latest data concerning HIV infection rates in people 27 to 39 years old in the U.S. The A.P. article included the following: women "are four times less likely to be infected," and the infection rates are 1 in 139 in white males vs. 1 in 1,667 in white females; 1 in 33 black men are infected, while 1 in 98 black women are infected. The news release is based on the latest data from the Centers for Disease Control and Prevention (Science 1995; 270: 1372). The article in Science included other data of importance, summarized on page 1375 as: "...a central observation is that AIDS incidence increased much more rapidly in recent years among younger individuals born in 1960 or later than among older individuals." This was followed by: "Any proposed model must explain these qualitatively different epidemic curves." The following diagram shows the two curves; it is taken from the Science article. It represents the incidence of AIDS as cases per month from 1982 to 1994.

AIDS Incidence by Year

I intend to propose a model to explain the two curves above. The reason for these two distinct curves is that the HIV infects people of reduced DHEA availability as a result of two causes, that is, people naturally low in DHEA and people of high testosterone, which reduces the availability of their DHEA. However, in order to do this, I must first explain why differences in race and sex occur. Differences in infection rates between sexes and races result from differences in DHEA and testosterone. Men produce more testosterone than women; black men produce more testosterone than white men, and black women produced more testosterone than white women. As I stated earlier in this treatise, my work suggests testosterone reduces the availability of DHEA. That is, testosterone increases use of DHEA for "testosterone target tissues." Testosterone stimulates transcription of genes which affect other genes. This is a "gene cascade," which eventually produces the effect of testosterone on target tissues. DHEA is used during this cascade of transcription. This increased use (competition) of DHEA for these decreases availability of DHEA for the immune system.

Remember that glucocorticoids reduce the loss of CD4+ cells; an effect I attribute to antagonism of DHEA action on these cells. Increasing testosterone should produce a similar effect by diverting DHEA, away from reducing CD4+s, to use by testosterone target tissues. Since there is reason to expect that using non-micronized, oral DHEA increases testosterone much more than DHEA, it fits that non-micronized DHEA raises CD4+s slightly (Journal of Acquired Immune Deficiency Syndromes 1993; 6: 459). The actions of the glucocorticoids and testosterone are quite different in our bodies, but they have a similar effect on CD4+ in HIV disease. That is, they both reduce the actions of DHEA on these cells.

The effects of periods of reduced DHEA and the effect of testosterone are readily seen in hemophiliacs. Using my chart, below, in hemophiliacs with AIDS, increased resistance to AIDS has been found to be highest during Period C, with increased susceptibility during Periods A, B, and E-F (The New England J. of Medicine 1989; 321: 1141). Periods A, B, E, and F are all times of declining DHEA availability. The investigators also found a slight decrease in resistance to AIDS during Period D. Period D includes puberty, the onset of large productions of testosterone. This decrease in resistance in Period D, a time of rising DHEA, occurs because of testosterone.


DHEA during the Human Life-span


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. (This chart is based on data from Adrenal Androgens, A.R. Genazzani, Raven Press, 1980.)

Men produce much more testosterone than women. Black women produce more testosterone than white women (unpublished results from the University of Tennessee, Medical School). Hence, men are more easily infected than women, and black women are more easily infected than white women. Testosterone is significantly higher in healthy black males compared to healthy white males (J. National Cancer Institute 1986; 76: 45). Black males produce more testosterone than any other group. Therefore, higher levels of testosterone increase susceptibility to HIV infection and worsen the symptoms of AIDS. It is known that "AIDS patients are disproportionately black (26%) and Hispanic (13%), compared with the proportions of blacks (12%) and Hispanics (6%) in the U.S. population." (JAMA 1989; 261: 201) and "The prevalence [of HIV] among black teenaged applicants (1.06 per 1000) was greater than among white (0.18 per 1000) or Hispanic (0.31 per 1000) teenaged applicants [to the military]" (JAMA 1990; 263: 2074). This also explains the "...unexpected finding that under the same social conditions, blacks are apparently infected more readily by Mycobacterium tuberculosis than whites" (The New Eng. J. Med. 1990; 322: 422). Increased HIV seropositivity in blacks and Hispanic intravenous drug abusers (IVDAs) is not due to more needle sharing; white IVDAs share needles more frequently than these minorities (JAMA 1987; 258: 1475).

Women are known to have a more aggressive immune system. I suggest this is due to lower testosterone and higher DHEA in women. Women are known to have less DHEAS than men. This may be due to the "X-linked steroid sulfatase" found on the X chromosome. (A steroid sulfatase removes the sulfate group from a steroid sulfate; this makes DHEA out of the steroid sulfate, DHEAS.) The unusual aspect of this steroid sulfatase is that it is active on both X chromosomes (Proceedings of the National Academy of Sciences USA 1987; 84: 4519). Women have two X chromosomes, men one. Since DHEAS may be the only steroid hormone produced as a sulfate, women would produce more DHEA than men. Therefore, females should react with a greater DHEA response upon HIV infection. Women are able to produce more DHEA from DHEAS, and white women produce the least testosterone of all of these groups. This explains why "Prevalence [of HIV infection] was lowest in white women" (Science 1995; 270: 1374). The ratio of DHEA to testosterone affects infection rates dramatically. ("Dehydroepiandrosterone uniquely sulfated (DHEAS) prior to export into the plasma..." (European J. Immunology 1990; 20: 793; also see Review of Medical Physiology, 16th. ed., Lange Medical Publications, 1993, page 329.)

Men are more readily infected by the HIV than women. Since DHEA naturally begins to decline around age 25 (Period E), mortality from AIDS should concentrate in men over 25. The so-called "incubation period" of AIDS results from early infection, followed by sickness and death, which begins to occur when DHEA begins to decline. Consider the chart of DHEA during the human life-span, above, and the following quotations.


"More than 90% of the AIDS-related mortality occurs in men, with nearly 75% in those 25 to 44 years old." (Science 1988; 239: 611)
"Once AIDS has developed, age continues to be a factor for the worsening of the disease. Large studies in New York and San Francisco have shown decreased survival times for persons with AIDS over 40 years of age." (J. Gerontology 1990; 45: M77)

In 1985, I hypothesized that reduced DHEA causes vulnerability to AIDS and that homosexual males produce low DHEA, because of conversion of part of their DHEA to estrone. I suggest that the combination of low DHEA and increased estrone cause the similarities in the brains of male homosexuals and the heterosexual females. A 1992 French study of homosexual men reported that estrone was 30-50% higher in all groups of HIV infected patients in addition to all also having low DHEAS (JAIDS 1992; 5: 841). It is now known that some homosexual men are vulnerable to the HIV and AIDS, while others have been exposed, but did not seroconvert (Science 1992; 257: 1032). The following chart demonstrates that some homosexual men have DHEA above the heterosexual population, while others produce very low levels (Biological Psychiatry 1973; 6: 31, after Fig. 3).


DHEA in Heterosexual and Homosexual Men

I suggest that homosexual men who produce high DHEA are not vulnerable to HIV infection, low DHEA individuals are vulnerable to HIV infection; those of very low DHEA develop AIDS. Those with higher levels of testosterone will be at increased risk. The higher DHEA in the heterosexual population should protect against HIV infection. Since some heterosexuals are low DHEA and high testosterone, abstinence, or safe sex, is very important.

I just found, today, July 18, 2014, the following research which directly supports my explanation of DHEA and seroconversion levels described in the paragraph above. “Pubmed,” the search engine of the National Library of Medicine did not go public until 1996. I would have loved to have had this when I predicted the DHEA levels and seroconversion (the mentioned paragraph above.)

Journal of Infectious Disease. 1992 Mar; 165(3): 413-8.

Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men.

Mulder JW1, Frissen PH, Krijnen P, Endert E, de Wolf F, Goudsmit J, Masterson JG, Lange JM.


The steroid hormone dehydroepiandrosterone (DHEA) has been reported to protect against certain viral infections in animal models and to be a modest inhibitor of human immunodeficiency virus type 1 (HIV-1) infection in vitro. Serum DHEA levels were determined in 41 asymptomatic HIV-1-seropositive subjects, who progressed to AIDS within 5 years after entering a cohort study, in 41 HIV-1-seropositive controls, who remained asymptomatic, and in 41 HIV-1-seronegative controls. At entry, DHEA levels were higher in the seronegative group (median, 13.3 nmol/l) than in either the seropositive nonprogressors (median, 9.2 nmol/l; P = .01) or the progressors (median, 7.2 nmol/l; P less than .001). DHEA levels in the progressors approximately 5 months before the diagnosis of AIDS were lower than the levels in the nonprogressors after the same follow-up (median, 5.6 vs. 8.8 nmol/l; P = .007). DHEA levels less than 7 nmol/l and CD4+ cell counts less than 0.5 x 10(9)/l both proved to be independent predictors for disease progression in HIV-1-infected men.

"Although derived from independent samples and subject to different biases, these three survey methods yielded a consistent pattern of HIV-1 epidemiology on this campus, whereby the overall prevalence of infection was low and confined to members of high-risk groups, despite the common occurrence of behaviors that might facilitate sexual transmission of HIV-1 among many other students." (Am. J. Epidemiology 1991; 133: 2)

The two different curves in the "AIDS Incidence by Year" chart, above, represent two populations of reduced DHEA availability and differences in testosterone production. A major component of my theory of human evolution is that increases in testosterone were involved in the changes that resulted in the formation of Homo sapiens. I stated at the end of my treatise on this subject that: "Human evolution is viable and unyielding today and affects every aspect of our lives." What I meant by that statement, and will expand later in another part of this website, is that testosterone levels continuously affect human populations. That is, the levels of testosterone in groups of people rise and fall cyclically. Testosterone is rising throughout the world at this time. I think a sign of this is that human sperm counts are currently dropping world-wide (see "Causes Sought for Sperm-count Drop," Science 1994; 265: 309). High testosterone has advantages and disadvantages; one of the disadvantages is that it reduces available DHEA and increases vulnerability to viruses and other infectious agents. The current epidemic of HIV infections is the result of this rise in testosterone.

I think testosterone must reach a "critical" level in a society before negative consequences accrue. (Prior to this, increasing levels of testosterone are beneficial.) This level was first reached prior to the 1960s; this period was the start of noticeable changes in our society that I attribute to significant increases in people of higher testosterone. The mechanism is simple. People of higher testosterone are more sexual and reach puberty earlier than those of less testosterone. Therefore, they produce more children at an earlier age. People of higher sex drive seek out people with higher sex drives. The consequence of this is an increase, each generation, in people of higher testosterone, who are more vulnerable to infections. This group produces the line in the chart labeled "Born in 1960 or later." Since they reach puberty earlier with time, they are affected earlier by testosterone. This shortens the time to HIV infection and AIDS. This is why this line shows a continued increase in AIDS incidence in younger individuals. The other line, labeled "Born in 1959 or earlier," results from people who are not reproducing rapidly. Therefore, this line is leveling off and possibly declining.

In humans and chimpanzees, HIV infection results in a rapid decline in CD4+ T lymphocyte counts. The decline of CD4+s in chimps is transient, and CD4+s routinely return to normal levels without progression to AIDS (Journal of Medical Primatology 1993; 22: 194). Chimps are readily infected with the HIV by way of injected HIV-infected human tissues, but chimps do not develop AIDS. I suggest levels of DHEA are directly responsible for vulnerability to HIV infection, the CD4+ response to HIV infection, and AIDS. DHEA is higher, and testosterone lower, in chimpanzees than humans (chart below). Therefore, humans are vulnerable to HIV infection and AIDS, while chimpanzees are not.


This chart is derived from: human: separate data in Adrenal Androgens, A.R. Genazzani, Raven Press, 1980; and chimpanzee: J. Reproduction and Fertility Supplement No. 28, 1980, from Text-fig. 5, page 137; this reference also contains data concerning testosterone in chimps and humans.

The HIV starts the decline of DHEA in people of low DHEA availability. I define aging as loss of DNA transcription. Since DHEA is necessary for transcription, loss of DHEA, around age 25, is the beginning of aging. People who die of AIDS produce very little DHEA; they are dying of premature aging, the early loss of DHEA. DHEA is very low in people with AIDS, and it is very low in aged people who require care in nursing homes. It is even lower in those who require total care.


"Mean DHEAS was significantly lower in the nursing home men than in the community men. Plasma DHEAS was subnormal in 40% of the nursing home residents and in only 6% of the community subjects. Plasma DHEAS was subnormal in 80% of the nursing home men who required total care." (J. Am. Ger. Soc. 1990; 38: 421)

The cause for nursing home care for people with AIDS, and the men of the study, above, is the same. They do not produce enough DHEA, from DHEAS, to maintain their bodies and their autonomy. AIDS is a disease of the ability to produce DHEA. No one would bring this purposefully on themselves anymore than they would choose to age prematurely. AIDS is not a vengeful act of God or a racist conspiracy. We have to understand that real physiological differences exist between the sexes, the races, and those with different sexual preferences. These differences result in different abilities and susceptibilities, physically and psychologically. To not accept this is to deny the possibility of a treatment for AIDS, and, perhaps, an understanding of many other disease processes.


". . .DHEA can inhibit the replication of AZT-resistant as well as wild-type HIV-1. Since the main targets for DHEA are metabolic and cellular signaling pathways leading to HIV-1 replication-activation, DHEA should be effective against multidrug-resistant strains of HIV-1. Combined with recently discovered immunoregulatory properties, the finding that DHEA is able to inhibit replication of both wild-type and AZT-resistant HIV-1 suggests that in vivo DHEA may have a much broader spectrum of action than originally anticipated." (Biochemical Biophysical Research Communications 1994; 201: 1424)

New Ideas About AIDS That I Have Posted To AIDS-Related Newsgroups

Protease Inhibitors and DHEA

I contend that protease inhibitors produce their effects by reducing production of DHEA. My work suggests that low DHEA results in vulnerability to HIV infection. If DHEA is sufficiently high, the infection is removed prior to antibody formation. That is, infected T cells are identified, attacked, and destroyed immediately. This occurs before the antibody sequence can occur. Their is evidence that DHEA increases significantly during the early phases of HIV infection (Journal of Acquired Immune Deficiency Syndromes 1992; 5: 841).

As I just suggested, I think this is the normal response to infection; in people with high DHEA, this finishes the job. In the citation just given, it is also found that in all individuals in the study, the backup supply of DHEA, called DHEA sulfate (DHEAS), is lower than controls. This indicates that the initial response of DHEA to the infection is never sufficiently high for a complete removal of the virus, and these individuals cannot replenish their supply of DHEA to ever reach the proper level. Another paper, in 1993, found that DHEAS levels were significantly low.


"When analyzed by clinical subgroups, significant differences were also found with a decrease in DHEA-S levels seen in persons with more advanced illness." (Am. J. Med. Sci. 1993: 305: 79)

If the levels of DHEA cannot ever reach the concentration sufficient to complete the removal of HIV-infected cells, the DHEA response becomes chronic. That is, the DHEA response persists, because it is chronically stimulated by infected cells.

Is this hypothesis correct?

Well, it would predict that some individuals exist whose DHEA level is high enough to eradicate the HIV. Individuals have been identified who are proven to have been exposed to the virus, but did not develop even the antibody response. Below this, one should see differences in DHEA levels according to response to the virus. That is, individuals who respond dramatically to the virus will use their DHEA more rapidly for their response than those who respond less actively with their DHEA. How can the response be identified? As I suggested, a sufficient DHEA response will remove infected CD4s. If, however, the response becomes chronic, the numbers of CD4s should lessen at the very same time that DHEA is reduced. You see, the longer this chronic killing of CD4s occurs, the more DHEA is needed. DHEA is low in HIV+ and lower in AIDS (Journal of the American Medical Association 1989; 261: 1149). Is this due to DHEA, I think so. When DHEA is given to a group that has never been exposed, the CD4s decline (American Journal of Obstetrics and Gynecology 1993; 169: 1536). Additionally, it is known that exercise increases DHEA. When forty to 60-year old men perform anaerobic exercise, their CD4 decrease (Int. J. Sports Me. 1995; 16: 2). DHEA increases cause CD4s to decrease. The CD4 reduction should occur in other viral infections for the same reason. For example, one study found this pattern in HIV infection and also in infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients (AIDS 1995; 9: 561).

If I am correct, DHEA should be lower in those that constantly reduce their CD4s, than in those that reduce their CD4 less rapidly. That is, DHEA should be used most in those that kill the most CD4s. This is directly supported in the following quotation.


"The steroid hormone dehydroepiandrosterone (DHEA) has been reported to protect against certain viral infections in animal models and to be a modest inhibitor of human immunodeficiency virus type 1 (HIV-1) infection in vitro. Serum DHEA levels were determined in 41 asymptomatic HIV-1-seropositive subjects, who progressed to AIDS within 5 years after entering a cohort study, in 41 HIV-1-seropositive controls, who remained asymptomatic, and in 41 HIV-1-seronegative controls. At entry, DHEA levels were higher in the seronegative group (median, 13.3 nmol/l) than in either the seropositive nonprogressors (median, 9.2 nmol/l; P =.01) or the progressors (median, 7.2 nmol/l; P less than .001). DHEA levels in the progressors approximately 5 months before the diagnosis of AIDS were lower than the levels in the nonprogressors after the same follow-up (median, 5.6 vs. 8.8 nmol/l; P = .007). DHEA levels less than 7 nmol/l and CD4+ cell counts less than 0.5 x 10(9)/l both proved to be independent predictors for disease progression in HIV-1-infected men." (J. Infect. Dis. 1992; 165: 413)

My work suggests that DHEA is directly involved in replication and transcription of DNA. Anything that interferes with the availability of DHEA will reduce transcription of DNA. One of HIV characteristics, since it is a retro virus, is that its genes are transcribed when the DNA of the host cell is transcribed. Reducing DHEA in a person should reduce the viral transcripts. Ritonavir dramatically reduces the plasma HIV-1 RNA and increases CD4 counts in the person, i.e., in vivo (New England Journal of Medicine 1995; 333: 1528).

I suggest ritonavir causes these effects by inhibiting production of DHEA. Inhibiting DHEA will stop the response of DHEA to infected CD4s. This will stop the removal of CD4s. If DHEA is reduced enough, transcription of HIV DNA within infected CD4s will also slow, or stop. Therefore, the plasma levels of HIV RNA will decrease dramatically. While PubMed will not pull up "ritonavir" and any word associated with the liver, or liver enzymes, various AIDS groups have reported that ritonavir inhibits a liver enzyme called P 450. Another protease inhibitor, L-754,394, designated as a potent anti-HIV agent, can be found by PubMed to cause inhibition of this enzyme group. There are no studies of these protease inhibitors and the adrenal glands, the source of DHEA. It takes a lot of ritonavir, in the human, not in a tissue culture dish, to produce the effects that I think are due to reductions in DHEA. I suspect that it takes this much drug to effectively close down the P450 group of enzymes in the adrenal gland. It has been suggested that loss of P450c17 in the adrenal gland with age is the cause of the normal loss of DHEA with age. "These results suggested that the expression of P450c17 mRNA decreased in aged bovine adrenal, which may cause the age-associated decline in biosynthesis of adrenal androgen." (Gerontology 1991; 37: 262)

There are other indications that the protease inhibitors are producing their effects by closing down production of DHEA within the body, but, for sake of brevity, I will close with this: Ritonavir may be producing its effects by reducing DHEA.


Apoptosis in AIDS - Apoptosis in AIDS is due to loss of DHEA

Whenever I am researching applications of my theory of DHEA in a particular subject, I always see if research exists regarding the subject at issue during times when I know DHEA is declining, naturally. One of these times happens to be during aging. I found the following regarding aging and apoptosis.


"The rate of apoptotic cell death was found to be elevated with age in both diet groups; however, the rate of apoptosis was significantly and consistently higher in the diet-restricted mice, relative to the ad libitum-fed mice, regardless of age." (Am. J. Pathol. 1995; 147: 20.)

It is known that reducing calories (diet restriction) reduces DHEA. Aging also reduces DHEA. (I think the natural loss of DHEA of aging is the cause of aging.) This means to me that loss of DHEA increases apoptosis. DHEA is reduced as AIDS progresses (this is in J. Acquired Immune Deficiency Syndromes 1992; 5: 841 and Am. J. Med. Sci. 1993; 305: 79). If I am correct, the increase in apoptosis in HIV disease should increase with progression. This is the case:


"Altogether these observations indicate that the increased susceptibility to apoptosis of peripheral T cells from HIV-infected persons correlates with disease progression and support the hypothesis that the chronic activation of the immune system occurring throughout HIV infection is the primary mechanism responsible for this cell deletion process." (J. Immunol. 1996; 156: 3509)

I think the loss of DHEA of AIDS is the cause of increased apoptosis in AIDS. I will go further and explain the mechanism in some more detail. First, I have to say that my theory, of 1985, suggested that the natural glucocorticoid, cortisol, evolved as a modulator of DHEA. That is, our natural cortisol acts to inhibit the actions produced by DHEA. I think this developed from the "fight or flight mechanism." This mechanism, however, affects other areas of our physiology.

During the first part of HIV infection, my work suggests that DHEA increases to activate the immune response. I think AIDS is due to the loss of DHEA. In many cases, phenomena that cause DHEA to increase, also cause cortisol to increase. That is, they are often produced simultaneously. However, they can be separated, and AIDS is one example. In AIDS, cortisol production continues. In the following quotation, both DHEA and cortisol are both significantly increased during the first phases of AIDS, but as DHEA declines, cortisol increases. The decline in CD4 counts parallels the decline in DHEA. Group I has a count of "more than 500/microliter," group 2 is "between 350 and 500/microliter," group 3 is "between 200 and 349/microliter," and group 4 is "less than 200/microliter."


"...and DHEA levels were significantly lower in group 2, group 3 (p<0.01) and group 4 (p<0.05) than in controls. Cortisol levels were significantly increased in groups 1 and 4 (p<0.05)..." (Eur. J. Endocrinol. 1995; 133: 418)

So, as DHEA production is reduced and cortisol is increased, the CD4 counts decline, probably due to apoptosis. The synthetic hormone, prednisone, is used to produce the effects of cortisol. Prednisone is a glucocorticoid. If loss of DHEA results in apoptosis, then increased cortisol should also increase apoptosis. This is the case, using prednisone. As you read this, keep in mind that DHEA is known to stimulate IL-2 in lymphocytes (Eur. J. Immunol. 1990; 20: 793). You can read this in full by looking up "More on Protease Inhibitors (Ritonavir works by reducing DHEA)." that was posted to, Sept. 14, 1996.


"PDN [prednisone] blocks PBL [peripheral blood lymphocytes] growth in the G1 phase of cell cycle and inhibits IL-2 receptor (IL-2R) expression and IL-2 secretion. Apoptosis is clearly increased by PDN in PHA-activated human PBL, and the apoptotic effect of PDN is stronger on CD8(+) than on CD(+)T lymphocytes." (Clin. Exp. Immunol. 1996; 103: 482.)

A number of investigators have also decided that DHEA may have "antiglucocorticoid" activity. Of course, I think that glucocorticoids should be labeled as having "anti-DHEA" activity. "The conclusion is that DHEA acts acutely as an antiglucocorticoid and exerts its effect in different glucocorticoid-sensitive systems." (Am. J. Med. Sci. 1992; 303: 366)


"We conclude that DHEA can act acutely as an antiglucocorticoid in the young obese Zucker rat and hypothesize that its chronic anti-obesity effect may reflect, at least in part, a chronic antiglucocorticoid activity." (Int. J. Obes. 1992; 16: 579)
"The results of this study have provided further insight into the mechanism of action of DHEA in this experimental model. The ability of DHEA to preserve immune function in severely thermally injured mice appears to extend beyond an antiglucocorticoid activity." (Endocrinology 1995; 136: 393)

The increased DHEA upon infection of the HIV, activates the immune system. My primary principle is that DHEA is necessary for transcription and replication of DNA. Since the HIV is a retrovirus, that becomes part of the T cell DNA, the increased DHEA due to infection, increases the viral load. As DHEA is "used up," cortisol production increases and the T cells decline due to apoptosis.