TOPIC:

The Causes of AIDS

This article was written in June 2000
and posted during the Internet Discussion
of the South African Presidential AIDS Advisory Panel

1. A PROPOSAL FOR THE PHISIOLOGICAL PATHOGENESIS OF AIDS

Five types of immunological stressor agents can alter the functioning of the immune system: chemical, physical, biological, mental, and nutritional. Numerous facts illustrate the incremental growth of these agents in recent decades, as well as their diversity throughout countries and continents (1-3).

Our soil, water, air, and food are polluted with numerous chemical, physical, biological, and nutritional stressors. We are all exposed to stressor agents either involuntarily through the conditions under which we are obligated to live or voluntarily through life styles that we have chosen (1-3).

AIDS occurs in groups of people who¾ through their living conditions or life styles¾ are more heavily exposed than others to the multiple, repeated, and chronic actions of immunological stressor agents (4-11).

These stressors can produce toxicity (immunotoxic effect) and can activate the regular molecular and cell networks (immunogenic effect) when acting on immunocompetent cells. Both immunotoxic and excessive immunogenic effects (over stimulation of immune responses) induce degeneration of cells and the functioning of the immune system (7-10).

AIDS is the most severe of all acquired immunodeficiencies, secondary to multiple, repeated, and chronic exposures to immunological stressors. These progressive and continuous deleterious actions upon the immune system bring the individual to a collapse of immunological functions, with the subsequent and simultaneous appearance of infections, neoplasias, and metabolic disturbances. In addition to acting upon the immune system, stressor agents alter functioning of practically all other bodily systems and organs.

Graph #1 shows a schematic summary of this proposal for the physiopathogenesis of AIDS (7,9).

Chemical [2] and biological [1] stressors produce degenerative-immunogenic effects [6] on immunocompetent cells. On the other hand, physical [3], mental [4], nutritional [5], and chemical [2] stressors, produce degenerative-immunotoxic effects [7] on these same cells.

The immunogenic [6] and immunotoxic [7] effects on cells involved in the immune response [8] are responsible for a variety of alterations upon different steps of the immune response, such as; disturbances in antigen processing [10], lymphocyte activation [11], lymphocyte proliferation [12], lymphocyte differentiation [13], cytokine production [14], cytotoxic effect [15], and antibody production [16].

Additionally, the immunogenic [6] and immunotoxic [7] effects on other immunocompetent cells, those of the bone marrow, peripheral blood, and other tissues, are translated into a variety of alterations in cell division [17], phagocytosis [18], natural killer-cell activity [19], complement system [20], and other immune networks [21], also related to the immune response.

The severe physiological alterations of cells involved in the immune response [8], as well as alterations of other immunocompetent cells [9], are responsible for the deficiency of the three main functions of the immune system: defense [22], homeostasis [23], and surveillance [24].

Following this, certain infectious agents [25] find a unique opportunity to grow within the deficiency of the defensive functions [22], and generate a variety of infectious diseases [28], termed opportunistic infections. The deficiency of the homeostasis functions [23], depending on the physiological status of the tissues and organs of the individual [26], can be responsible for a variety of metabolic disturbances and conditions [29]. The deficiency in surveillance functions, together with the presence of carcinogen agents and all other factors involved in the carcinogenesis process, are responsible for the occurrence of neoplasias [30].

2. A PROPOSAL FOR THE MOLECULAR PATHOGENESIS OF AIDS

At a molecular level, AIDS is caused by the accumulation of free radicals, especially oxidizing agents, in all systems, organs, and tissues, but principally within the cells and chemical reactions of the immune system (4,8,10-22). As a consequence, the clinical manifestations of AIDS¾ opportunistic infections, tumors, and metabolic disturbances and conditions¾ as well as the severity of the illness are directly proportional to the levels of free radicals, especially oxidizing agents in the tissues of the AIDS patient.

Graph #2 is a illustration of this proposal (7,9).

Chemical [2] and biological [1] stressors, through an immunogenic effect [6] with an over stimulation/activation of immunocompetent cells of the immune response [8], stimulate the production of free radicals [9]. On the other hand, physical [3], mental [4], nutritional [5], and chemical [2] stressors cause an immunotoxic effect [7], either by acting directly as free radicals themselves [10], or through an indirect effect [11] can stimulate their production [12], contributing to a critical excess of free radicals [13]. The excess of radicals, together with over-saturation of the oxidation protective mechanisms [14], causes damage to immunocompetent cells through different chemical reactions [15], with degeneration of immunocompetent cells and reactions [16]. As a result, a collapse of all immunological functions will manifest itself with the subsequent and simultaneous appearance of opportunistic infections, metabolic conditions, and neoplasias. In other words, AIDS [17].

3. A PROPOSAL FOR THE DEFINITION OF AIDS

I propose to define AIDS as a toxic and nutritional syndrome, the most severe and profound of all acquired immunodeficiencies, due to multiple, repeated, and chronic exposures to immunological stressor agents. These stressors cause degenerative immunotoxic and immunogenic effects on immune cells and reactions, with the accumulation of free radicals, especially oxidizing agents, in all body systems but principally in the organs and tissues of the immune system. These progressive and continuous deleterious actions upon the immune system bring the individual to a collapse of immunological functions, with the subsequent and simultaneous appearance of infections, neoplasias, and metabolic conditions. Simultaneous with acting on the immune system, stressor agents alter the functioning of practically all other systems and organs. The continuation of this process eventually causes the death of the person (7-10).

The diverse clinical manifestations of AIDS are the direct consequence of the physiologic and molecular pathogenesis of the syndrome. The distribution of immunological stressors varies within the groups of people at risk for AIDS. This fact is the primary explanation for the great deal of variation in the clinical manifestations of AIDS within the groups of people at risk for it. While altering the immune system, the exposure to stressor agents also causes damage to practically all systems, organs and tissues of the body. This is another factor in explaining the great deal of variety in the clinical manifestations of AIDS within the groups at risk for it. In AIDS, not only the immune system collapses, but all other systems as well (7-10).

In brief, AIDS is neither an infectious disease nor is sexually transmitted. It is a toxic and nutritional syndrome caused by the alarming worldwide increment of immunological stressor agents.

REFERENCES

Giraldo RA. AIDS and Stressors I: Worldwide Rise of Immunological Stressors. Toxicology Letter Supplement 1/78. 1995: s34.

Giraldo RA. AIDS and Stressors I: Worldwide Rise of Immunological Stressors. In: AIDS and Stressors: AIDS is Neither an Infectious Disease nor is Sexually Transmitted. It is a Toxic-Nutritional Syndrome Caused by the Alarming Worldwide Increment of Immunological Stressor Agents. Medellín, Colombia: Impresos Begón, 1997: 23-56.

Giraldo RA. El Alarmante Incremento Mundial de Agentes Estresantes Inmunologicos. In: Ahumada C, et al. Relaciones Internacionales, Politica Social y Salud: Desafios en la Era de la Globalización. Bogotá, Colombia: Fundación Cultural Javeriana, 1998: 49-73.

Papadopulos-Eleopulos E. Reappraisal of AIDS – Is the Oxidation Induced by the Risk Factors the Primary Cause? Medical Hypothesis 1988; 25: 151-162.

Duesberg PH. AIDS Acquired by Drug Consumption and other Noncontagious Risk Factors. Pharmac Ther 1992; 55:201-277.

Duesberg PH, Rasnick D. The AIDS Dilema: Drug Diseases Blamed on a Passenger Virus. Genetica 1998; 104: 85-132.

Giraldo RA. AIDS and Stressors II: A Proposal for the Pathogenesis of AIDS. Toxicology Letter Supplement 1/78. 1995: s34.

Giraldo RA. AIDS and Stressors III: A Proposal for the Natural History of AIDS. Toxicology Letter Supplement 1/78. 1995: s35.

Giraldo RA. AIDS and Stressors II: A Proposal for the Pathogenesis of AIDS. In: AIDS and Stressors: AIDS is Neither an Infectious Disease nor is Sexually Transmitted. It is a Toxic-Nutritional Syndrome Caused by the Alarming Worldwide Increment of Immunological Stressor Agents. Medellín, Colombia: Impresos Begón, 1997: 57-96.

Giraldo RA. AIDS and Stressors III: A Proposal for the Natural History of AIDS. In: AIDS and Stressors: AIDS is Neither an Infectious Disease nor is Sexually Transmitted. It is a Toxic-Nutritional Syndrome Caused by the Alarming Worldwide Increment of Immunological Stressor Agents. Medellín, Colombia: Impresos Begón, 1997: 97-131.

Giraldo RA, et al. Is It Rational to Treat or Prevent AIDS With Toxic Antiretroviral Drugs in Pregnant Women, Infants, Children, and Anybody Else? The Answer is Negative. Continuum (London) 1999; 5(6): 38-52.

Dworkin B, et al. Selenium Deficiency in the Acquired Immuno-Deficiency Syndrome. J Parenteral Enteral Nutr 1986; 10:405.

Fabris N, et al. AIDS, Zinc Deficiency and Thymic Hormone Failure. JAMA 1988; 259: 839.

Papadopulos-Eleopulos E. Looking Back on the Oxidative Stress Theory of AIDS. Continuum (London) 1998/9; 5(5): 30-35.

Papadopulos-Eleopulos E, et al. Oxidative Stress, HIV and AIDS. Res Immunol 1992; 143: 145-148.

Turner VF. Reducing Agents and AIDS – Why Are We Waiting? Med J Austr 1990; 153: 502.

Favier A. The Place of Oxygen Free Radicals in HIV Infections. A collection of papers presented at a conference on "The place of oxygen free radicals in HIV infection", Les Deux Alpex, France, January 1993. Chem Biol Interac 1994; 91: 91-100.

Salvain B, Mark AM. The Role of Oxidative Stress in Disease Progression in Individuals Infected by the Human Immunodeficiency Virus. J Leukocyte Biol 1992; 52: 111.

Greenspan HC. The Role of Oxidative Oxygen Species, Antioxidants and Phytopharmaceuticals in Human Immunodeficiency Virus Activity. Med Hypothesis 1993; 40: 85.

Piette J et al. Molecular Mechanisms of Virus Activation by Free Radicals. Collection of 5 articles presented at a conference on "The place of oxygen free radicals in HIV infection", Les Deux Alpes, France, January 1993. Chemico-Biological Interactions 1994; 91: 79-132.

Shallenberger F. Selective Compartimental Dominance: An Explanation for a Noninfectious Multifactorial Etiology for Acquired Immune Deficiency Syndrome (AIDS), and a Rationale for Ozone Therapy and Other Immune Modulating Therapies. Med Hypothesis 1998; 50: 67-80.

Passi S. Progressive Increase of Oxidative Stress in Advancing Human Immunodeficiency. Continuum (London) 1998; 5(4): 20-26.

Roberto A. Giraldo
www.RobertoGiraldo.com

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

"Co-factors" Cause AIDS

This article was written in June 2000
and posted during the Internet Discussion
of the South African Presidential AIDS Advisory Panel

Since it has never been scientifically proven that HIV destroys the immune system and causes AIDS (1), investigators who enthusiastically defend HIV as the cause of the syndrome have proposed a vast variety of agents as helpers, or ‘cofactors", of HIV in the genesis of AIDS (2,3). However, these "cofactors" are by themselves causal agents of immunodeficiency and can generate AIDS with or without the presence of a positive result on the antibody tests for HIV (4,5). I prefer to call the so-called "cofactors" immunological stressor agents that can have chemical, physical, biological, mental, and nutritional origin (6,7).

The following are some of the agents that have been proposed as "cofactors" for HIV: alcohol, cocaine, heroine, morphine, marihuana, cigarette smoking, amphetamines, volatile inhalants like "poppers", environmental chemical pollutants, allergens, CMV, herpes virus type 1, 2, & 6, herpes zoster, EBV, adenovirus, retroviruses other than HIV, hepatitis A, B, & C viruses, papovavirus, mycoplasmas and other superantigens, tuberculosis, leprosy, malaria, trypanosomiasis, filariasis, other tropical diseases, sexually transmitted diseases, semen, blood, factor VIII, anxiety, depression, lack of sleep and rest, exhaustible exercise, unsanitary conditions, poverty, malnutrition, and several vitamin deficiencies (2,3,8-11).

Let us see briefly how multiple, repeated and chronic exposure to immunological stressor agents¾ "cofactors" ¾ can degenerate the immune system and cause AIDS:

1. Role of Chemical Stressors in Immunodeficiency

Practically every single medicament from the following groups have been found to have immunotoxic properties: antibiotics; antifungal, antiviral, and antiparasitic agents; tranquilizers, antiepileptics, antiparkinson, and anesthetics; antihypertensive, anti- anginal, and antiarrhythmic drugs; gastrointestinal medications; antidiabetics, antithyroid drugs, and sex hormones including oral contraceptives; antiallergics; bronchodilating agents; anticoagulants, drugs acting on fibrinolysis, blood expanders, clotting factors, and inhibitors of platelet aggregation; non-steroidal anti-inflammatory drugs, corticosteroids, antirheumatismal, and anti gout drugs; and immunodepressive and immunomodulating drugs such as antitumoral drugs and medications to avoid graft rejection (12-14). The immunotoxicity of AZT has been solidly documented (15-18).

Industrial, chemical, and environmental pollutants are another important source of various abnormalities upon lymphocyte activation, proliferation and differentiation, cytokine production, cytotoxic effect, antibody production, phagocytosis, natural killer cell activity, complement, etc., (19,20). Additionally, immunotoxicity has been found in practically every single chemical that has been tested from the following groups: heavy metals, pesticides, aliphatic and aromatic hydrocarbons and derivatives, alcohols, phenols, and derivatives, airborne pollutants including diesel engine emissions, nitrogen dioxide, ozone, sulfuric acid and food additives and preservatives (13,14,21).

The adverse effects of alcohol and other drugs on the immune system have been documented since the beginning of the last century (22). There is a growing body of human and animal evidence concerning the immunotoxicity of tobacco smoke, alcohol, marijuana, cocaine, heroine, alkyl nitrites, met amphetamines, qualones and other street drugs (23-30). These facts in part form the scientific base for the "drug-AIDS hypothesis" (15,16,31,32).

Chemical stressors can act as free radicals or stimulate the production of them (33-35).

2. Role of Physical Stressors in Immunodeficiency

There is evidence that a variety of physical stressors lead to immunodeficiency. Lymphocytes are much more radiosensitive than macrophages and plasma cells, and alterations of the immune cells are in a dose-dependent fashion. Radiation victims frequently succumb to infection (36,37).

Ultraviolet B radiation (UV) has often been implicated in local and systemic immunosuppression (38). UV exposure decreases the counts of total and helper T lymphocytes with inversion of T4/T8 ratio (33). It also decreases plasma carotenoids, potent antioxidants (39).

Exposures to other non ionizing radiations such as electromagnetic fields, visible light, infrared, radio frequencies and microwaves, lasers, and very low and extremely low radiation frequencies have been shown to increase the risk of degenerative diseases and certain cancers (40-44).

Vibration, heat, and high altitude stressors are also connected to degenerative diseases in which the immune system is known to play protective roles (45-46).

Free radicals have been clearly connected with physical stressors and cell injury (33,35,47,48).

3. Role of Biological Stressors in Immunodeficiency

The immunogenic properties of the components of human semen are known to induce chronic stimulation of the immune system with subsequent immunosuppression (49,50). Lymphocytotoxic autoimmunity is proposed as a mechanism for this phenomenon (51). Passive anal intercourse is recognized as a strong risk factor for AIDS (52-55), even for HIV-negative individuals (47).

Blood and its components are known to be immunosuppresive (56). It has been suggested many times that the immunological abnormalities occurring in hemophiliacs are secondary to the immunogenic properties of foreign proteins in the whole blood, in commercial clotting factor VIII, or to factor VIII itself (56-61). The hemophilia immunologic dysfunctions are obviously proportional to the lifetime dose of therapy received (61). Immunodeficiency has been described multiple times in HIV-negative hemophiliacs (62,63). On the other hand, no immunosuppression has been observed in hemophiliacs treated with available purer factor VIII preparations (64). These facts in part form the base for the "foreign-protein-hemophilia AIDS hypothesis" (58).

A necessary prerequisite for any infectious agent developing potential pathogenic properties is host immunodeficiency (65). On the other hand, and as a consequence of the host-infectious-agent relationships, immunosuppression, especially of the cell-mediated immunity, occurs during all infectious diseases (66). This is particularly valid in intracellular infections¾ gonorrhea, listeriosis, legionellosis, brucellosis, chlamydial infections, mycoplasma infections, rickettsial infections, salmonellosis, tularemia, yersinia infections¾ and with all viral diseases (66,67). Immunodeficiency is also the rule during infections with poly-immunogenic organisms leading to granuloma formation, such as spirochetes (syphilis, bejel, yaws, pinta); mycobacteries (tuberculosis, leprosy); fungi (dermatomycosis, sporotrichosis, chromomycosis, histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, cryptococosis, pneumocystosis, aspergillosis, mucormycosis, candidiasis); protozoa (toxoplasmosis, malaria, leishmaniasis, trypanosomiasis, amoebiasis, giardiasis); helminths (intestinal helminthes, cysticercosis, hydatidosis, filariasis, schistosomiasis, fluke infestations, toxocariasis) (66,68-71).

The role of parasites and infections as a cause of immunosuppression in the underdeveloped world has been addressed many times (8,10,11,72).

Reactive free radicals have been implicated in the generation of immunodeficiency during the course of infectious diseases (73-75).

4. Role of Mental Stressors in Immunodeficiency

Since the times of Galen (200 AD) it has been of public knowledge that the mind can influence the body (76), particularly in disorders related to immunity (77). Different immunological abnormalities have been found in people under psychosocial stress (78). For example, anxiety and depression decrease lymphocyte counts and functions (79). Academic stress lowers natural killer cell activity, blastogenesis, and interferon production (80). Bereavement decreases lymphocyte proliferative response to mitogen and lowers natural killer cell activity (81). DNA repair capability in lymphocytes is highly impaired by mental distress (82).

Only in the last three decades have the mechanisms that allow mental stressors to cause immunodeficiency been clarified (77,83-86).

Lymphocytes are known to produce various hormones and neurotransmitters, originally believed to be produced only by endocrine glands and neurons (87,88). At the same time, lymphocytes have receptors for all types of hormones and neurotransmitters, including endorphins and encephalins (87). Neurons and cells from endocrine glands have receptors for lymphokines (87). Therefore, brain, mind, endocrine glands, and lymphoid tissues are biochemically interconnected (89), structuring a critical part of our defense activities. Furthermore, all types of stressors (chemical, physical, etc.) share pathways during any stress response to them (90).

The issue of mental stress as an immunodepressive agent has been addressed many times in relation to the onset, course, and prognosis of AIDS (78,91,92).

5. Role of Nutritional Stressors in Immunodeficiency

The effects of malnutrition on lymphoid organs were first described during the middle of the 19th century (93). Lymphoid tissues are particularly vulnerable to the damaging effects of malnutrition, and lymphoid atrophy is a prominent feature in nutritional deprivation (94). Cell division is a very singular characteristic of the functioning of immunocompetent cells. All types of immune cells and their products, such as interleukins, interferons, and complement, are known to depend on metabolic pathways that employ various nutrients as critical co-factors for their actions and activities (94). Most of the host defense mechanisms are altered in protein-energy malnutrition [PEM], as well as during deficiencies of trace elements and vitamins (95).

Patients with PEM have impaired delayed cutaneous hypersensitivity, poor lymphocyte proliferation response to mitogens, lower synthesis of lymphocyte DNA, reduced number of rosetting T lymphocytes, impaired maturation of lymphocytes seen through an increased deoxynucleotidyl transferasa activity, decreased serum thymic factor, fewer CD4+ cells, decreased CD4+/CD8+ ratio, impaired production of interferon gamma and interleukin 2, altered complement activity (especially reduction of C3, C5, factor B and total hemolytic activity), poor secondary antibody response to certain antigens, reduced antibody affinity, impaired secretory immunoglobulin A response, decreased antibody affinity, and phagocyte dysfunction (94).

Human malnutrition is usually a composite syndrome of multiple nutrient deficiencies. However, isolated micronutrient deficiencies do happen. Vitamin A deficiency results in reduction in the weight of the thymus, decreased lymphocyte proliferation, impaired natural killer cell and macrophage activities, and increased bacterial adherence to epithelial cells (96). Vitamin B6 deficiency produces failure of several components of both cell-mediated and humoral immune responses (94). Vitamin C deficiency impairs phagocytosis (97) and cell-mediated immune reactions (102). Vitamin E deficiency also alters immune responsiveness (94). Zinc deficiency generates lymphoid atrophy, reduces lymphocyte responses and skin delayed hypersensitivity (94). Copper and selenium deficiencies impair T and B lymphocyte functions (94). Dietary deficiencies of selected amino acids such as glutamine and arginine also alter immunity (94).

Intrauterine malnutrition causes prolonged, even permanent, depression of immunity in offspring (98,99).

Considerable data implicate excess lipid intake in the impairment of immune responses (100). The potential for free radical damage is dependent in large part on the level of potentially oxidizable fatty acids, mainly polyunsaturated fatty acids (PUFAs) in the diet (33). High levels of dietary PUFAs have been shown to be immunodepressive. Dietary fats may undergo free radical-mediated oxidation prior to ingestion, as can occur when foods are fried (33). Animals fed oxidized lipids show marked atrophy of the thymus and T lymphocyte dysfunctions (100,101).

At the molecular level, the damage to immunocompetent cells by several nutritional deficiencies (Vitamin A, Vitamin C, Vitamin E, zinc, copper, zelenium deficiencies) is caused by increased free radicals through oxidative stress (94,102).

As Jain and Chandra (9) have found, "...there is an uncanny similarity between the immunological findings in nutritional deficiencies and those seen in AIDS". The role of nutritional stressors in AIDS has been addressed many times (103,104).

6. Role of Free Radicals in Immunodeficiency

Free radical reactions of special significance to immunological phenomena are, for example, many oxidizing agents that can abstract a hydrogen atom from thiol groups to form thiyl radicals. Thiol groups are important for enzyme activities, receptor functions, disulphite links in immunoglobulins, and T cell activation and proliferation (105). The super oxide anion radical can react with nitric oxide resulting in loss of endothelium-derived relaxing factor activity (106), which is important in the inflammation/disinflammation process. Methionine oxidation can cause protein damage with subsequent changes in immunogenicity (107). Proteolysis can be increased by free radical damage (108). The per oxidation of lipids by reactive free radicals produce many biological modulators as, for example, the 4-hydroxy-alkelans which produces strong chemotactic activity for phagocytes (109), alters the adenyl cyclasa system, increases capillary permeability, and alters lymphocyte activation (110). Lipid hydroperoxides, also from per oxidation of lipids, alter lymphocyte activation (110). Conditions favoring lipid per oxidation may result in chemo taxis of leukocytes, protein modification, immune complex injury, and cell death (105).

Free radicals are produced over the regular immune system network. Despite the beneficial effects of the inflammation responses, they can also aggravate existing tissue damage by releasing free radicals. When uncontrolled, initiated by an abnormal stimulus, or occurring for prolonged periods of time, inflammation may become the disease process (111). It is critical for optimal immune responses that there be a balance between free radical generation and antioxidant protection (33). During phagocytosis by polymorphonuclear leukocytes for example, super oxide anion radicals are released (112). These oxygen free radicals can oxidize thiol groups to thiol radicals, and can stimulate lipid per oxidation with the formation of H2O2, which is very significant in the mechanisms of cell injury (105). Oxygen free radicals produced during phagocytosis of immune complexes are associated with injury due to immune complexes (113).

It has been proposed several times that free radicals and specifically oxidizing species play important roles in the pathogenesis of AIDS (55,114-121).

7. Conclusions

I propose that at a physiological level, AIDS can be explained as a progressive degenerative alteration of different immune cells and immune metabolic reactions, secondary to multiple, repeated, and chronic exposures to immunological stressors. This degeneration can be caused by an immunotoxic effect of stressors on immunocompetent cells. Also, it can be the result of over stimulation/activation of the immune cells through an immunogenic effect. Many chemical and biological stressors can have an immunogenic effect on the immune cells and functions. Additionally, physical, mental, nutritional, and, again, chemical stressors can have an immunotoxic effect on the same cells and activities (4,5).

At a molecular level, AIDS is the result of alterations of immunocompetent cells and immune metabolic reactions due to an excess of free radicals, especially oxidizing agents. Since 1988 Eleni Papadopulos-Eleopulos has been elegantly describing the role of oxidizing agents in the pathogenesis of AIDS (119).

AIDS is neither an infectious disease nor is sexually transmitted. It is a toxic/nutritional syndrome caused by the alarming worldwide increment in immunological stressor agents.

8. Trial Proposal

I propose the following experiments to find out the real role of immunological stressors¾ co-factors¾ in the causation of AIDS:

Have three groups of people: a) symptomatic AIDS patients; b) HIV-positive asymptomatic individuals; and c) very healthy HIV-negative individuals.

The AIDS patients as well as the HIV-positive asymptomatic groups should include individuals from all the groups at risk for AIDS; drug addicted and non-drug addicted gay males, IV and non-IV drug addicted individuals, prostitutes, hemophiliacs, blacks and Hispanics in the USA, Africans and Asians, children from developed and underdeveloped countries, AIDS-phobic people, and an occupational group. The normal individuals to be used as controls should match as closely as possible the individuals in the other two groups.

Retrospective trial¾ before starting any treatment the three groups should be checked for:

· Exposure to immunological stressors of chemical, physical, biological, mental, and nutritional origin. A questionnaire should be used to determine retrospectively past exposures to chemical, physical, biological, mental, and nutritional immunological stressors.

· Levels of oxidizing agents. Test all groups for the presence and levels of surrogate markers of oxidation.

· "HIV status." Test all individuals in each of the three groups with the ELISA, Western blot, and PCR tests.

· Immune system response capabilities. In addition to counting all the T and B cell subsets, it is necessary to evaluate the functioning status of lymphocytes, as well as all other immunocompetent cells, by tests such as lymphoblastotransformation, inhibition of migration, lymphocyte activation, etc. Test the levels of all components of the complement system. Test electrophoresis of proteins, immunoelectrophoresis, levels of serum immunoglobulins G, A, M, D, and E. Test for the presence of all types of autoantibodies, circulatory immune complexes, and skin test reactions. Test for Beta 2 microglobulin.

· Physiological status of all other systems. Run complete chemical, hematological, urine and stool profiles. Also test the status of the endocrine glands, liver, and kidneys. Determine levels of micronutrients such as B-complex vitamins, Vitamin C, betacarothene, vitamin E, selenium, zinc, magnesium, etc. Test Beta 2 microglobulin.

Prospective trial¾ follow the three groups for several years with periodic clinical and laboratory evaluation.

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