Articles

Acquired Immune Deficiency Syndrome (AIDS)

Introduction

In 1981, the first cases of symptomatic HIV (human immunodeficiency virus) infection were recognized as AIDS (acquired immunodeficiency syndrome). It has been established that HIV infection is caused by a virion belonging to the family Retroviridae that invades the CD4+ lymphocytes. These lymphocytes are the "helpers" that modulate the actions of other cellular components of the immune system. The eventual loss of CD4+ lymphocytes is the underlying pathophysiology that leads to AIDS. With the breakdown of the immune system, an environment for establishing chronic infections is created which can be the cause of death in the HIV-infected patient. AIDS is now the fifth leading cause of death among adults between the ages of 25 and 44. (1)

For a person to become infected with HIV, there must be direct contact by way of the blood stream or mucous membrane of a non-infected person with infected blood, semen, or vaginal secretions. Intimate sexual contact is the primary route of HIV transmission. HIV can also be transmitted from mother to child perinatally, through transfusions, IV drug abuse, or exposure to infected blood or blood products in the health care setting. There is evidence that has demonstrated a lack of HIV transmission through casual and household contact. The half-life of the virus is only six hours, but an individual with moderate to advanced infection may produce hundreds of billions of viral particles each day.

HIV is a retrovirus that carries its genetic information in RNA rather than in DNA. The process of infection includes virus entry, reverse transcription, integration, gene expression, assembly, budding, and maturation. The stages of HIV reproduction proceed as follows:

    HIV enters a CD4+ cell. HIV is a retrovirus, meaning that the genetic information is stored on single-stranded RNA instead of the double-stranded DNA found in most organisms. To replicate, HIV uses an enzyme known as reverse transcriptase to convert its RNA into DNA. HIV DNA enters the nucleus of the CD4+ cell and inserts itself into the cell’s DNA. HIV DNA then instructs the cell to make copies of the original virus. New virus particles are assembled and leave the cell ready to infect other CD4+ cells.

A diagnosis of AIDS is made in individuals with the following criteria:

A CD4+ cell count of less than 200 cells per cubic millimeter (or CD4 T-lymphocyte percentage of total lymphocytes of less than 14%) and a laboratory-confirmed HIV infection; OR

A laboratory-confirmed HIV infection plus one of a list of additional clinical conditions that includes: candidiasis, invasive cervical cancer, cytomegalovirus disease, histoplasmosis, mycobacterium, recurrent pneumonia, salmonella septicemia, and wasting syndrome due to HIV.

Plasma HIV RNA levels indicate the magnitude of HIV replication and its associated rate of CD4+ T-cell destruction, while CD4+ T-cell counts indicate the extent of HIV-induced immune damage already suffered. Regular, periodic measurement of plasma HIV RNA levels and CD4+ T-cell counts is necessary to determine the risk of disease progression in an HIV-infected individual and to determine when to initiate or modify antiretroviral treatment regimens.

Statistic

Centers for Disease Control, 2004.

    The cumulative number of AIDS cases reported to CDC is 944,305. Adult and adolescent AIDS cases total 934,862 with 756,399 cases in males and 178,463 cases in females. Through the same time period, 9,443 AIDS cases were reported in children under age 13. Total deaths of persons reported with AIDS through 2004 are 529,113, including 523,598 adults and adolescents, and 5,515 children under age 13.

Joint United Nations Programme on HIV/AIDS, 2002.

    Today, 42 million people are estimated to be living with HIV/AIDS. Of these, 38.6 million are adults. 19.2 million are women, and 3.2 million are children under 15. An estimated 5 million people acquired the human immunodeficiency virus (HIV) in 2002, including 2 million women and 800,000 children under 15. During 2002, AIDS caused the deaths of an estimated 3.1 million people, including 1.2 million women and 610,000 children under 15. Women are becoming increasingly affected by HIV. Approximately 50%, or 19.2 million, of the 38.6 million adults living with HIV or AIDS worldwide are women.

Signs and Symptoms

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In the early stages of HIV infection, as viral levels increase, the infected individual may begin to experience symptoms of early infection.

Within the first 12 weeks of HIV infection, the patient may develop nonspecific symptoms that are similar to mononucleosis. These may include:

  • Fever
  • Fatigue
  • Lymphadenopathy
  • Maculopapular rash
  • Headache
  • Arthralgia/ myalgia
  • Nausea, vomiting, diarrhea
  • Night sweats
Symptoms last from several days up to two weeks, but then improve. After the active phase, viral levels may begin to fall and the patient may enter a latency period, during which the individual is symptom-free. Although patients generally feel better during the latency phase, the infection process continues with the eventual destruction of the host’s immune system.

A person infected with HIV may remain free of symptoms and in relatively good health for many years. Nonetheless, the virus continues to reproduce and depress the immune system. Eventually, individuals become vulnerable to opportunistic infections, leading to death. At this time, there is no vaccine or cure for AIDS.

Within approximately 6 months, an HIV antibody test may help confirm a diagnosis.After several years as immune function declines, individuals become vulnerable to opportunistic infections, leading to death.

Treatment Options

Conventional

New mutations of the virus result in a heterogeneous population of virus within the body. As drug therapy is introduced, susceptible strains are destroyed, but resistant strains may be allowed to grow uninhibited because of limited competition from other strains. As resistant strains predominate, antiretroviral resistance develops.

The use of potent combination antiretroviral therapy to suppress HIV replication to below levels of detection of sensitive plasma HIV RNA assays limits the potential for selection of antiretroviral-resistant HIV variants, the major factor limiting the ability of antiretroviral drugs to inhibit virus replication and delay disease progression. Therefore, maximum achievable suppression of HIV replication should be the goal of therapy.

The classification of antiretroviral agents used to treat HIV infection is based upon the stage of the life cycle of the cell that is being interrupted. The therapeutic goal of antiviral treatment is the suppression of viral replication, which will slow the decline of the total number of CD4+ lymphocytes. The development of opportunistic infections or malignancies may require that the goal be modified, but the clinical effectiveness of therapy or the clinical decline of the patient still needs to be monitored.

Fourteen antiretroviral agents have been approved by the FDA for use in HIV infection. Six are nucleoside analog reverse transcriptase inhibitors (NRTIs), five are protease inhibitors, and three are non-nucleoside reverse transcriptase inhibitors (NNRTIs). There is one combination product available that contains two NRTIs (lamivudine and zidovudine). These agents are listed in the table below.

Nucleoside Analogs (NRTI) Protease Inhibitors Non-nucleoside Analogs (NNRTI)
Zidovudine (AZT) Saquinavir Nevirapine
Didanosine (ddI) Ritonavir Delavirdine
Zalcitabine (ddC) Indinavir Efavirenz
Stavudine (d4T) Nelfinavir
Lamivudine (3TC) Amprenavir
Abacavir

The nucleoside analogs were the first effective antiretroviral agents to be approved for HIV therapy in the U.S. The NRTIs work by inhibiting the viral enzyme reverse transcriptase. They reduce replication of cell-included HIV viruses by inhibiting DNA chain elongation prior to insertion into the human genome. By incorporating themselves into the DNA of the virus, they stop the building process. The resulting DNA is incomplete and cannot create new virus. They do not interfere with the replication of HIV viruses once integration has occurred nor, are they active against "cell free" viruses.

Protease inhibitors work at the last stage of the virus reproduction cycle. The protease inhibitors suppress viral replication following insertion into the human genome. They work by inhibiting protease, the enzyme responsible for cleaving viral precursor polypeptides into mature and infective virions. They prevent HIV from being successfully assembled and released from the infected CD4+ cell. They act synergistically with reverse transcriptase inhibitors by interrupting HIV replication at separate stages of the viral cycle.

The newest class, nucleotide reverse transcriptase inhibitors, stops HIV production by binding directly onto reverse transcriptase and preventing the conversion of RNA to DNA. These drugs are called "non-nucleoside" inhibitors because even though they work at the same stage as nucleoside analogs, they act in a completely different way. They inhibit the catalytic reaction of reverse transcriptase that is independent of nucleotide binding. They are approved for use in combination with nucleoside reverse transcriptase inhibitors.

Recent evidence suggests that it is reasonable to try to suppress viral production as early and for as long as possible. Currently available FDA-approved antiviral combinations are powerful suppressers of viral replication, resulting in a 1.0 to 3.1 log reduction of HIV RNA. Since some patients who have had long-term HIV infection have not developed AIDS, a reasonable aim is to achieve significant suppression, although not complete eradication, of viral replication.

Compared with monotherapy, combination therapies are associated with improved survival in asymptomatic patients with intermediate-stage disease. Studies using newer agents in combination have shown even greater virologic potency and the ability to stabilize immunologic parameters. Three and four drug anti-HIV "cocktails" have become the standard of drug therapy.

In the past, the CD4+ lymphocyte count was used as the major marker for disease progression. Because of the changing relationship between CD4+ cell count and the incidence of opportunistic infections, practitioners are now using viral load as the main marker for HIV progression and for initiating antiretroviral therapy. HIV-infected persons, even those with viral loads below detectable limits, should still be considered infectious and should be counseled to avoid sexual and drug-use behaviors that are associated with transmission or acquisition of HIV and other infections.

Patients in the late stages of AIDS are often on complex multiple medication regimens. These medications can include antiretrovirals, anti-infectives for opportunistic infections, analgesics, antidepressants, nutritional support, growth factors, biologicals, chemotherapy, investigational medications, and others. It is important to understand all of the possible drug interactions and additive toxicities of medications used to treat AIDS in order to ensure patients of optimal therapeutic outcome and quality of life.

Nutritional Supplementation


Vitamin A

In one study, 16 AIDS and 12 HIV-positive patients showed greater levels of malnutrition and excreted a substantially larger amount of vitamin A in the urine compared to 11 healthy individuals in the control group. (2) Another study showed that low vitamin A levels could increase the mother-to-child transmission of HIV during fetal development. Out of 338 HIV-positive mothers, 74 mothers who transmitted HIV to their infants had lower concentrations of vitamin A in comparison to the 264 mothers who did not transmit the disease. (3) Therefore, it is advisable to monitor vitamin A levels in patients with HIV and AIDS and provide appropriate supplementation when necessary.


Vitamin B12

Serum vitamin B12 levels are frequently found to be low in (HIV)-infected patients. Patients with HIV and AIDS also frequently have problems with digestion and absorption, which can lead to deficiencies of vitamin B12 and other nutrients. Many of these patients are also found to have inadequate levels of vitamin B12-binding proteins, which can contribute to vitamin B12 deficiencies. In general, vitamin B12 levels tend to worsen as the disease progresses. Studies still have not yet been conducted to determine if vitamin B12 supplementation will increase the long-term survival of AIDS and HIV-infected patients. However, B12 levels should be evaluated and those who are deficient should receive proper supplementation in order to treat or prevent hematological and/or neurological symptoms. (4)

The authors of another study reported that a deficiency of vitamin B12 was associated with a decline in CD4 cell count. It was also determined that patients with lower initial vitamin B12 levels were more likely to have lower CD4 cell counts and accelerated HIV-1 disease progression. (5)


Vitamin C

Preliminary research and observation has noted that extremely high doses, 50-200 grams daily, can suppress the symptoms of the disease and can markedly reduce the tendency for secondary infections. (6) In order to assess the immunological and virological effects of short-term, high-dose antioxidant treatment in patients with HIV infection, 8 patients with HIV infection were given high doses of N-acetylcysteine (NAC) and vitamin C for 6 days. Though further study is warranted, the 5 patients with the most advanced immunodeficiency did experience a rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level as well as improvements in other measures. (7)

Vitamin C was found to be 60% depleted in the frontal cortex region of the brain in patients who had died of AIDS neurotoxicity. Ascorbic acid is known to suppress HIV virus replication and it also modulates glutamate neuronal activity. It is suggested that the low levels of ascorbic acid may make certain neurons more vulnerable to oxidative damage, which may contribute to the development of dementia. (8)


Vitamin E

In one study 28 serologically positive HIV patients and 11 healthy individuals, being the control group, were studied. Vitamin E levels were found to be considerably lower and urinary excretion of vitamin E considerably higher in patients with AIDS and HIV compared to healthy controls. Researchers suggest that vitamin E supplementation should be integrated into the existing medical therapy so that patients can maintain proper vitamin E levels. (9)

Other researchers report that dietary supplementation of vitamin E with current drug therapies such as Zidovudine (AZT), may improve the therapeutic efficiency of drugs and decrease the incidence of opportunistic infections that commonly develop in AIDS patients. It has also been suggested that therapeutic doses of vitamin E may also slow down the progression of the disease to AIDS, possibly by stimulating specific immune cells that are normally destroyed by the HIV infection. (10)


Selenium

Selenium is one of the most common nutrient deficiencies found in AIDS and HIV-infected patients. Selenium is a nutrient that is necessary for proper functioning of the immune system and it also functions as an antioxidant. Selenium levels are highly correlated with AIDS-related mortality. Also, the HIV virus utilizes selenium for some of its metabolic purposes, which may further deplete the patient’s selenium levels. Selenium supplementation has resulted in improved immune markers and lowered the amount of lipid peroxidation. (11)

AIDS and HIV-positive patients were also found to have significant impairments of antioxidant defense activity that is normally provided by selenium, and glutathione peroxidase. (12) These results suggest that selenium supplementation may prove beneficial as an adjuvant therapy for AIDS through reinforcement of endogenous antioxidant defense systems.


Zinc

Zinc is one of the most important nutrients for immune function. Deficiencies weaken the immune system and increase one’s susceptibility to infectious diseases. Many AIDS patients suffer zinc deficiency, which can cause significant decline in the biological activity of the thymic hormone known as thymulin. Providing patients with zinc sulphate supplementation resulted in an increase or a stabilization in the body weight and an increase of the number of CD4+ cells and the plasma level of active zinc-bound thymulin. Zinc supplementation also caused a substantial reduction in the frequency of opportunistic infections. These results suggest that zinc supplementation may be beneficial as an adjunct to AZT therapy in patients with AIDS. (13)

It should be noted that zidovudine (and presumable other similar AIDS-related drugs) cause zinc depletion. Thus, patients being treated with these drugs should definitely be monitored for zinc status. Appropriate levels of zinc supplementation can reduce the incidence of opportunistic infections and boost the overall functioning of the immune system. (14)


Beta-Carotene

Beta-carotene deficiencies are common in all stages of HIV/AIDS in both adults (15) and children. (16) Using a body mass index the nutritional status of 23 symptomatic HIV-infected children were compared with a control group of 36 uninfected children. Results were profoundly deficient serum beta-carotene levels of the symptomatic HIV-infected children which could have immunologic and clinical implications for children with this disease. Patients with the acquired immunodeficiency syndrome (AIDS) are characterized by a decrease in the number of T helper cells, a defect that is linked to the impaired immunologic competence. Vitamin A and its dietary precursor, beta-carotene, increase absolute T helper cell counts as well as indices of T cell function in both human and animal models.

When seven AIDS patients, in a single-blind, non-randomized clinical trial, were given beta-carotene the total lymphocyte counts rose by 66 percent, and CD4+ cells increased slightly, but insignificantly, in the entire group. Six weeks after the beta-carotene treatment, the absolute CD4+ cell count returned to pretreatment levels. These preliminary observations suggest that short-term treatment with beta-carotene may provide some therapeutic benefits in patients with AIDS. (17)


L-Carnitine

AIDS patients may have AZT induced myopathies and may have low carnitine status. (18) Supplementation with carnitine may also improve immune function. (19)


Coenzyme Q10 (CO-Q10)

AIDS patients were found to have lower levels of coenzyme Q10 compared to controls and the deficiency of CoQ10 increased with the increased severity of the disease. In a small trial, 7 patients with AIDS or ARC were treated with coenzyme Q10. Five of the 7 survived, making good symptomatic improvement with no opportunistic infection during 4-7 months. In spite of rather poor patient compliance, the authors felt that the treatment results were very encouraging and at times even quite remarkable. (20)

Patients with AIDS and ARC are known to have low ratios of T4/T8 lymphocytes. Continuous therapy with coenzyme Q10 enabled two patients with ARC to survived four to five years without any symptoms of adenopathy or infection. Coenzyme Q10 also causes an increase in the T4/T8 ratios in healthy subjects. The results of these small trials suggest that coenzyme Q10 is worthy of consideration in the treatment of AIDS and HIV-related diseases. (21)


Omega-3, Omega-6

It has been hypothesized that a relative deficiency in gamma-linolenic (GLA) and eicosapentaenoic acids (EPA) and their metabolites be associated with the development of AIDS. These polyunsaturated fatty acids (PUFAs) may be able to battle the virus destroying the enveloped viruses. Thus, there is a rationale for supplementation with these dietary PUFAs in the prevention, and possibly in the treatment of AIDS. (22)

In another study, it was noted that polyunsaturated fatty acids (PUFAs) can enhance the immune system in vivo and inactivate virus envelopes in vitro. Lipid profiles in patients with AIDS revealed that these patients had significantly reduced levels of the longer chain omega-3 fatty acids known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is suggested that normalizing these fatty acid levels in AIDS patients may provide beneficial therapeutic gains. (23)


Dehydroepiandrosterone (DHEA)

The use of DHEA for the treatment of AIDS is just beginning to be evaluated. Low serum concentrations of DHEA are associated with low immune function. It has also been suggested that a low levels of DHEA may be used to predict a decline in overall health status. (24)

In another study, researchers evaluated the relationship between serum dehydroepiandrosterone sulfate (DHEAS), free and total testosterone levels, and several other HIV illness markers. The results of the study confirmed that low serum DHEAS is increases HIV illness markers, such as viral load, and carries negative prognostic value. (25)


L-Glutamine

L Glutamine is a nonessential amino acid unless infection, trauma, wound healing, or gut disturbances are present. L glutamine is reported to reduce muscle catabolism and shifting the body into the anabolic mode. Glutamine contributes to healing the intestine when intestinal permeability is heightened. (26) , (27) L glutamine seems to improve NK cell activity as well as stimulating macrophages and cytokine production. (28)


Multivitamin

Malnutrition in AIDS and HIV-positive patients can cause or contribute to additional health problems and further weaken the immune system. It has been estimated that malnutrition affects between 50 and 90% of AIDS patients. (29) The nutritional deficiencies that frequently develop in patients with HIV infection and AIDS are serious and often contribute to death. Being malnourished further weakens patients’ health and immune system, which reduces their ability to comply with and respond to treatment. Early detection of malnutrition and proper nutritional intervention can reduce the problems caused by these conditions. It has been suggested that at any stage of disease, a Medical Nutrition program needs to be become a primary component of the therapy for AIDS and HIV-positive patients. (30) A multivitamin supplement showed health benefits in women infected with HIV. (31) A daily high potency multivitamin/mineral supplement will benefit most patients. For more advanced patients, intravenous nutrients may be required.


N-Acetyl Cysteine (NAC)

HIV-infected persons at all stages of the disease were found to have low plasma cystine and cysteine concentrations as well as reduced intracellular glutathione levels. Cellular cysteine levels affect a number of important factors such as intracellular glutathione levels, IL-2-dependent proliferation of T cells and inversely, the activation of the transcription factor NF-kappa B. Therefore, cysteine deficiency in HIV-infected persons may cause both cellular dysfunction and the over-expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 receptor alpha-chain, and beta 2-microglobulin. (32) N Acetyl Cysteine has doubled the life of AIDS patients vs the controls in a recent trial. (33)

When high doses of reduced glutathione were given in together with AZT to AIDS patients, the combination provided synergistic therapeutic benefits in a number of measured parameters. (34)


Lactobacillus, Bifidobacteria

Malabsorption and maldigestion are common problems in patients with AIDS. (35) These reactions can place added duress on their immune function, heighten symptoms and if the intestinal lining is compromised there may be a reduction in absorption of nutrients thus contributing to weight loss. Many physicians recognize that probiotics can be useful in helping to reestablish normal bowel function.


Vitamin B1

Several reports in the last several years have described brain lesions that resemble Wernicke's Encephalopathy in patients with AIDS. Utilizing the functional erythrocyte transketolase activation assay, researchers report finding thiamine deficiency in 9 out of 39 (23%) patients with AIDS or ARC (Aids-related complex). After ruling out alcohol abuse and Wernicke’s Encephalopathy, it was suggested that the thiamine deficiency in these patients was due to cachexia and catabolic deterioration that often accompanies AIDS. These results suggest that nutritional supplementation with thiamine should be considered as part of the treatment for patients diagnosed with AIDS or AIDS-related complex. (36)


Sterols (Sitosterol) and Sterolins (Sitosterolin)

There are many chemical constituents (termed phytochemicals) found in plant medicines that have beneficial pharmacological effects in humans. Some bioactive phytochemicals include tannins, resins, polysaccharides, saponins, glycosides and volatile oils among others. Recent literature has reported that two of these phytochemicals, sterols and sterolins (plant "fats"), occur naturally in fruits, vegetables, seeds and nuts are, have clinically beneficial effects in human subjects in many conditions.

Sterol is found in all plant-based foods, and sterolin is a glucoside moiety joined to the sterol chemical structure. Both sterols and sterolins were identified as early as 1922. In the natural state, these plant "fats" are bound to the fibers of the plant, making the sterols and sterolins difficult to be absorbed during the normal transit of digested food through our gut. Seeds are the richest source of the sterols and sterolins, but are usually removed during processing by the food industry.

Plant sterols and sterolins have been reported to be effective adjunctive agents in the management and treatment of disease states such as high cholesterol levels, benign prostatic hyperplasia, pulmonary tuberculosis and stress-induced immune suppression and HIV among others. (37) , (38) , (39) , (40) , (41) Some of the most promising uses of these plant "fats" is in the management of autoimmune disorders such as lupus, multiple sclerosis, rheumatoid arthritis and myasthenia gravis. Of note is that the sterols should be combined with sterolin in order to be an effective agent for the immune system. (42)

Sterols and sterolins have been reported to modulate the function of T-cells, significantly enhancing the proliferation of the CD-4 TH-1 cells and increasing the production of the interleukin 2 (IL2) and gamma-interferon (FN-g and IFN-y). (43) These results indicate that sterols and sterolins are adaptogenic in that they modulate the immune and stress response.

Care should be taken if an individual is taking immunosuppressive agents. Based on pharmacology, If an individual is taking hypocholesterolemic agents concurrently with plant sterols and sterolins, a dosage adjustment in the pharmaceutical medication may be necessary.

Herbal Supplementation


Arabinoxylane

Arabinoxylane is a polysaccharide dietary fiber formula from the outer shell of rice bran (hemicellulose B) that has been enzymatically modified with hyphomycetes mycelia from three different medicinal mushrooms: Shiitake, Kawaratake and Suehirotake. (44) Arabinoxylane shows great promise not only in immune support, but also in diseases of the immune system such as cancer and HIV. (45)

There have been several reports of a proprietary arabinoxylane extract’s ability to improve immunity. Arabinoxylane’s has been reported to improve the induction of Natural Killer (NK) cell activity in vitro and in vivo significantly, and actually continue to improve NK activity up to 6 months after cessation of therapy. (46) , (47) Dosages of 3gm daily have been used in these therapies. NK cells have been characterized as non-B cells or non-T cells lacking the characteristics of mature macrophages which develop from the bone marrow independently of thymic influence. (48) NK cells play a crucial role in tumor rejection, immune surveillance, resistance to infections, and immune regulation. (49)

Arabinoxylane has also been reported to: (1) increase tumor necrosis factor A (TNF-A) production, and (2) increase interferon-y (IFN-y) synthesis by peripheral blood mononuclear cells in vitro. (50) It was concluded that the high augmentory effect of arabinoxylane makes it a promising immunotherapeutic agent for treatment of various carcinomas.

Arabinoxylane has reported activity against HIV in vitro, inhibiting replication of the virus. (51) Arabinoxylane has been reported to inhibit HIV replication by: (1) inhibition of HIV-1 p24 antigen production in a dose dependent manner, (2) inhibition of syncytia formation. The author also reported that human ingestion of arabinoxylane at concentration of 15 mg/kg/day resulted in a significant increase in T and B cell mitogen response at 2 months after treatment.


Reishi Mushroom

Reishi mushroom is called the "mushroom of immortality" in China and has been used as a tonic and strengthening medicine for thousands of years. Uses in traditional healing include increasing intellectual capacity and memory, promoting agility, and lengthening the life span. (52) Reishi is reported to have some of the most active polysaccharides in the plant kingdom. Polysaccharides are claimed to have immunomodulating activity. Reishi is also reported beneficial as an antioxidant, antihypertensive, hypoglycemic, antiviral, and hepatoprotective agent.

Reishi extracts have been reported to significantly increase the life span of fruit flies by significant amounts (16-17 percent) in several studies, and also enhancing endurance and cellular oxygenation. (53) Reishi has been reported to inhibit superoxide activity and hydroxyl radical activity in vitro, supporting its role as an antioxidant. (54) The constituents with antioxidant activity have been reported to include the triterpenes. (55) Polysaccharides in reishi have been reported several clinical studies to have antiherpetic properties, and has been used in treating herpes (56) and postherpetic neuralgia, decreased pain dramatically in two patients with postherpetic neuralgia recalcitrant to standard therapy and two other patients with severe pain due to herpes zoster infection. (57) The triterpenoid constituents in reishi have reported anti-HIV-1 and anti-HIV-1-protease activity in vitro. (58)


Shiitake Mushroom

Shiitake mushroom grows on the trunks or stumps of trees, with the medicinal part used being the mycelia or immature growing stage of the mushroom. Shiitake has been used in Traditional Chinese Medicine for thousands of years as a medicinal agent. Shiitake mycelia has been reported to be immunomodulating in the following ways: 1. Activation of macrophages, promoting recognition of antigens and information transmission to the T-helper cells, increasing rate of phagocytosis, 2. Increase and reinforce interleukin-1 production, thereby activating the T-helper cells, 3. Promotes the mitosis and proliferation of B-lymphocytes, 4. Increases antibody production. (59) , (60)

Isolated extracts of shiitake (lentinan) also have been reported to be effective in treating HIV and retroviral infections in vivo and in vitro. (61) The water-soluble pepetidomannan EPS-3 has been reported to inhibit the replication of the Human Immunodeficiency Virus in vitro. (62) When compared to AZT and DHT as antiviral agents against HIV-1, HIV-2, and HTLV-I virus, an isolated extract of shiitake mycelia performed equally with the standard antiviral agents in blocking the cell-free infection of HIV-1 and HIV-2; however, only the lentinan polysaccharide preparation blocked the cell-to-cell infection by HIV-1, HIV-2 and HTLV-I. (63) Recently, a new proteinase inhibitor was isolated from shiitake. (64) Shiitake preparations should be studied further in the possibility of managing and treating HIV infection.

Shiitake has been reported to increase lymphokine-activated killer (LAK) cell activity in vitro. (65) Treatment with shiitake mycelia preparation increased the LAK cell concentration by 50%, and reduced the dose of recombinant interleukin 2 (rIL-2) by 50%. This data suggests that shiitake preparations can be used as bio-regulators in LAK cell therapy in tumor treatment. Lentinan (b-1-3-glucan), has been reported to increase host immune responses, with effectiveness for the patients with advanced or recurrent stomach or colo- rectal cancer in combination with chemotherapeutic agents such as mitomycin. Lentinan has been administered as an agent for supportive therapy in patients with advanced breast carcinoma with effectiveness. (66) The b-1,3-glucan (lentinan) reversed tumor growth when injected in mice. It acts by stimulating the immune system, rather than by direct action on the tumor. (67) Lentinan activates the alternative complement pathway, stimulating the macrophages, thus inhibiting tumor growth. It also may activate interleukin-1 secretion, which helps trigger T lymphocytes. Shiitake is also believed to stimulate interferon production. Shiitake significantly inhibited the toxic immunosuppressive effects of cancer drugs such as cyclocy-tidine, when taken with them. Lentinan restores impaired enzyme activity of X-proline-dipeptidyl-aminopeptidase in the serum of mice with tumors. Because of its large molecular size, lentinan may not be absorbed efficiently when taken orally, but studies report enough is absorbed to elicit a positive pharmacological response.

Recently, aqueous shitake extracts have been reported to decrease IL-1 production and apoptosis in human neutrophils in vitro, as measured by ELISA and flow cytometry. (68) The extract was further separated into high and low molecular weight components, and it was found that the low molecular weight component retained the activity of the whole extract. This further suggests that the active substance is a novel compound distinct from lentinan, the well-studied high molecular weight anti-tumour agent found in shiitake.


St. John's Wort

St. John’s wort has gained a great deal of attention for its use in minor depression. Its popularity has stemmed from its extensive use by physicians in Europe as an agent of choice in the treatment of mild to moderate depression. Additionally, hypericum has been used as an antiviral agent, including HIV. (69) It has been reported that, in sufficient blood levels, it may decrease HIV titer and it may increase T-killer cell activity. (70) Hypericum and the xanthrones are thought to be responsible for the antiviral activity. (71) Although its antiviral action has been questioned, several studies report this potential action. (72) , (73) The drawback is that large doses must be taken and this is where side effects related to St. John’s wort (such as phototoxicity) can occur. A recent study has reported no positive effect when using St. John’s wort as an antiretroviral agent. (74)

Recent literature has reported cytochrome P-450 enzyme-inducing activity of St. John’s wort in human studies. Interactions between St. John’s wort and anticoagulants, indinavir, cyclosporin, digoxin, ethinyloestradiol/desogestrel and theophylline have occurred. (75) The mechanism of action was believed to be liver enzyme induction and subsequent alterations of drug levels by the herb. Also, several reports have suggested that concurrent use of St. John’s wort and SSRIs may result in "serotonin syndrome", including sweating, tremor, confusion, flushing and agitation. (76) , (77) Use St. John’s wort with caution if individuals are on these medications. A study recently reported that St. John’s wort decrease the level of the protease inhibitor indinavir significantly. If an individual is taking protease inhibitor medications, do not use St. John’s wort as a therapy for HIV. (78) Also, since anti-retroviral agents are hepatically metabolized, use extreme caution when taking these medications and St. John's wort. Only use under the direct supervision of a physician.


Olive Leaf

Olive leaf extract has been reported to be an effective antimicrobial agent against a wide variety of pathogens, including Salmonella typhi, Vibrio parahaemolyticus and Staphylococcus aureus (including penicillin-resistant strains), Klebsiella pneumonia and Eschericha coli, causal agents of intestinal or respiratory tract infections in man. (79) The component usually associated with olive leaf’s antimicrobial properties is oleuropein. (80) , (81) Oleuropein also has been reported to directly stimulate macrophage activation in laboratory studies. (82)

Olive leaf extract has reported antiviral activity, reportedly caused by the constituent calcium elenolate, a derivative of elenolic acid. (83) , (84)


Larch Arabinogalactan

Arabinogalactans are a class of long, densely branched polysaccharides of the 3,6-beta-D-galactan type with molecular weights ranging from 10,000-120,000. Because of the immune-enhancing properties, LA is receiving increased attention as a clinically useful immunomodulating agent. (85) LA may be a good therapeutic choice for individuals with recurrent immune system problems, including colds and influenza, chronic fatigue and viral hepatitis among others. LA has also been used with positive success in children, specifically in otitis media. (86)

LA is reported to enhance immunity by various methods. Studies report that LA stimulates natural killer cell cytotoxicity, enhances other functional aspects of the immune system, and inhibits the metastasis of tumor cells to the liver. (87) Mechanism of action of LA in immunomodulation include:

    Natural Killer (NK) Cytotoxicity: It has been reported that decreased NK cell activity may be linked to a variety of chronic diseases including cancer, (88) chronic fatigue syndrome (CFS), (89) , (90) prostate cancer, (91) autoimmune diseases such as multiple sclerosis, (92) and viral hepatitis. (93) Investigators reported that LA stimulated NK cell cytotoxicity against a tumor cell line in vitro. (94) The larch arabinogalactan-mediated enhancement of NK cytotoxicity does not appear to be initiated directly, but may be governed by the cytokine network. Generally, LA pretreatment induces an increased release of interferon gamma, tumor necrosis factor alpha, interleukin-1 beta and interleukin-6. Results suggest the increase in interferon gamma was most responsible for the observed enhancement of NK cytotoxicity. Reticuloendothelial and Complement Activation: Low to middle molecular weight (5,000-50,000) arabinogalactan polysaccharides isolated from larch and non-larch sources have been reported to have immunostimulating properties, including the ability to activate phagocytosis and potentiate reticuloendothelial system action. (95) , (96) Several arabinogalactans (isolated from non-larch sources) have also been shown to have anti-complement activity. (97)


Milk Thistle

Historically, milk thistle was used as a digestive tonic; a general tonic for the spleen; stomach and liver; for the gallbladder; to promote bile flow; and as a stimulant for milk flow in nursing mothers. (98) Milk thistle is also used as a hepatoprotective agent and for the treatment of various liver disorders. (99) , (100) The active constituents of milk thistle are a combination of three substances, silybin, silydianin, and silychristin, which collectively are reported to exert hepatoprotective activity. (101)

Silymarin reportedly acts by inhibiting the passage of toxins into the liver cells, by altering the membranes of the hepatic cells and by stimulating regeneration of new liver cells through increased protein synthesis. (102) Silymarin has been demonstrated to increase glutathione content in the liver by more than 35 percent, increasing its antioxidant capacity. (103) Milk thistle is also reported to inhibit inflammatory enzymes, known as leukotrienes, which would normally lead to the destruction of liver tissue. (104) Because of its reported liver enzyme and cell protection capabilities, it is used in a wide variety of conditions, such as chemical-induced liver damage (including industrial chemicals, alcohol and pharmaceutical drugs), hepatitis, gallbladder dysfunctions, and psoriasis. (105) , (106)

Aromatherapy

Aromatherapy for AIDS

Aromatherapy and essential oil therapy may be useful in treating AIDS from the perspective of improving quality of life and providing an enhanced sense of well being. (107) The use of aromatherapy and massage as an effective method of reducing stress in pediatric aids patients suggests that this type of extended care may help reduce anxiety related to hospitalization and may prove to be a beneficial addition to nursing care. (108)

Oils that may prove useful include Roman Chamomile (Chamaemelum nobile) and Lavender (Lavendula augustifolia).

Caution: Essential Oil therapies should not be used during pregnancy or lactation unless under the supervision of a trained aromatherapist or other practitioner.

Diet & Lifestyle

    Get required rest Lymphatic massage may be of benefit Eat a yeast free diet Avoid refined sugar Avoid gluten containing carbohydrates Select nutrient dense foods such as vegetables fruits, whole grains

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Adrenal Function Profiles

Adrenal reserve capacity is compromised in AIDS. (109) Stress activates the HPA axis and has impact on the immune system, particularly through the adrenal hormones. In assessing the HPA axis, adrenal functional abnormalities are relatively simple to identify and address (e.g. when compared to hypothalamic dysregulation or pituitary imbalance).

Organic Acids

Certain biochemical intermediates reflect sufficiency of nutrient cofactors (vitamins of the B complex [pyridoxine has a direct affect on T4 levels (110) ], magnesium, some amino acids, and many others) that are important in carbohydrate, neurotransmitter and fatty acid metabolism, among other vital functions. Organic acids analysis is a useful method for measurement of biochemical intermediates in urine. Stress response can deplete enzymes dependent on these cofactors for synthesis. Chronic stress may also interfere with proper digestion and result in increased allergic response (111) and imbalanced gastrointestinal flora. A subset of organic acids, the dysbiosis markers, may provide useful information regarding gastrointestinal pathogens that can contribute to immune compromise.

Mineral Analysis

The evaluation of essential and/or toxic elements can be of use in the evaluation of AIDS. Essential mineral imbalances can affect nearly any tissue and organ resulting in a myriad of concurrent disorders. Trace element deficiencies can disproportionately affect enzyme systems that are used in regulatory substrates resulting in amplified disease conditions. Toxic elements can be particularly damaging as a result of toxicity responses and inhibition of essential nutrient-dependent mechanisms.

Fatty Acids

Dietary polyunsaturated fatty acids (PUFA) are primarily composed of omega 3 and omega 6 fatty acids. PUFA are vital in the production of eicosanoids – components involved in regulating inflammatory response, blood vessel leakage, lipid accumulation, immune cell response, and optimal control of virtually every body tissue (112) .

Testosterone

Hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality. (113)

Clinical Notes

Assess GI health. Chronic candidiasis can have ravage the individual. Organic acids urine is one way to assess this. It is important to maintain GI integrity for absorption of nutrients as well as improving immune response. Decreased absorption of nutrients will reduce immune functionality. Supporting the cellular energy pathways and detoxification process is also an important factor.

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