FOR THE TREATMENT AND PREVENTION OF AIDS
African Development Community (SADC)
Health Ministers Meeting
Johannesburg, South Africa
January 20-21, 2003
By Roberto Giraldo1
1. Nutritional immunology.
2. Nutritional deficiencies and HIV/AIDS.
3. Nutritional deficiencies and the progression of HIV-positive individuals to AIDS.
4. Nutritional deficiencies and the “transmission” of HIV/AIDS.
5. Reactivity on tests for HIV in sub-Saharan Africa not explained by sexual or vertical transmission.
6. Oxidative stress and HIV/AIDS.
7. Nutritional and antioxidant deficiencies in the pathogenesis of AIDS.
8. Nutritional and antioxidant therapy for the prevention and treatment of AIDS.
1. NUTRITIONAL IMMUNOLOGY.
The effects of malnutrition on lymphoid organs were first described during the middle of the 19th century (1). Lymphoid tissues are particularly vulnerable to the damaging effects of malnutrition, and lymphoid atrophy is a prominent feature in nutritional deprivation (2-5). 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 (5,6). Most of the host defense mechanisms are altered in protein caloric malnutrition (PCM), as well as during deficiencies of trace elements and vitamins (2,4,7,8).
Patients with PCM 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 (2-7).
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 (8-11). Vitamin B6 deficiency produces failure of several components of both cell-mediated and humoral immune responses (2,4,7). Vitamin C deficiency impairs phagocytosis and cell-mediated immune reactions (12). Vitamin E deficiency also alters immune responsiveness (2,4,7). Zinc deficiency generates lymphoid atrophy, reduces lymphocyte responses and skin delayed hypersensitivity (2,4,7). Copper and selenium deficiencies impair T and B lymphocyte functions (2,4,7). Dietary deficiencies of selected amino acids such as glutamine and arginine also alter immunity (2,4,7).
Beta-carotene is a provitamin A carotenoid that may enhance T-cell and B-cell immune function, possibly through conversion to vitamin A or by acting as an antioxidant (13,14). Daily supplementation of beta-carotene among elderly volunteers has led to an increase of T-lymphocytes and cells with interleukin-2 receptors (13). Furthermore, supplementation with beta-carotene or vitamin A is associated with enhanced cellular immunity in both humans and animals (13,15-17). In addition, vitamin A enhances humoral immunity, demonstrated by antibody response to tetanus (18) and measles (19) antigens.
Supplementation with vitamin E in healthy elderly people significantly improved lymphocyte proliferation, IL-2 production, DTH, and response to T-cell-dependent vaccines, and reduced the incidence of infections (20,21).
Vitamin C is an antioxidant that plays a role in immune responses and the formation of connective tissues. Proliferation of T and B lymphocytes increased following supplementation with vitamin C (22), and increased levels of vitamin C have been associated with lower rate of infections (23).
Several B-complex vitamins have roles in immune functions. Vitamin B6 deficiency in healthy elderly individuals significantly reduced the total number of lymphocytes, lymphocyte proliferation, and IL-2 production in response to mitogens; these defects were corrected following B6 repletion (24). Riboflavin deficiency has been shown to impair the ability to generate antibodies (25). Clinical studies show that individuals with low serum vitamin B12 had impaired neutrophil function, while animal studies indicate that vitamin B12 supplements are associated with enhanced humoral and cellular immune responses (25).
Selenium is necessary for the proper functioning of the enzyme glutathione peroxidase, which acts as an antioxidant (26). Selenium deficiency is associated with impaired phagocytosis, decresed CD4 T-lymphocytes, and the occurrence of opportunistic infections (26). Selenium supplementation as parenteral nutrition improved immune response in patients with chronic gut failure (27).
Zinc plays an important role in the growth, development, and function of natural killer cells, macrophages, neutrophils, and T and B lymphocytes (28). Zinc supplementation has resulted in significant reductions in the severity of diarrhea, malaria, and acute respiratory infections among children (29).
Intrauterine malnutrition causes prolonged, even permanent, depression of immunity in offspring (30,31).
Considerable data implicate excess lipid intake in the impairment of immune responses (32). 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 (32). 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 (32). Animals fed oxidized lipids show marked atrophy of the thymus and T lymphocyte dysfunctions (32).
At the molecular level, the damage to immunocompetent cells by several nutritional deficiencies (PCM, Vitamin A, Vitamin C, Vitamin E, zinc, copper, zelenium deficiencies) is caused by increased free radicals through oxidative stress (8-11,32,33).
2. NUTRITIONAL DEFICIENCIES AND HIV/AIDS.
Since the beginning of the AIDS epidemic, researchers have provided scientific evidence that supports the possibility that AIDS can be effectively prevented, treated, and overcome by guaranteeing an optimal nutritional status to the individual or the patient (34,35). However, it seems that propaganda spread by pharmaceutical companies to commercialize antiretroviral medications has prevented these ideas from being widely accepted, despite the toxicity of these medications.
Early in the AIDS era, well recognized researchers in the field of nutrition and immunology, such as Dr. Ranjit Kumar Chandra, noticed that: “There is an uncanny similarity between the immunological findings in nutritional deficiencies and those seen in acquired immunodeficiency syndrome, AIDS” (34).
“There is a similarity between the immune deficiency, multiple infections, and severe weigh loss seen in AIDS patients, and the association of protein caloric malnutrition (PCM) with reduced resistance to infection observed in malnourished children, particularly in the Third World.” “It is also possible that nutritional deficiency may play a significant role in the clinical course of the immunodeficient state.” “These similarities between AIDS and PCM suggest that nutrition may contribute to the immunodeficient state. The immunodeficiency in children with PCM can be reversed by nutritional rehabilitation, which suggests that restoration of nutritional state may be a useful adjunct to therapy for AIDS patients” (36).
As described above, the immunological alterations found in PCM are practically identical to those of AIDS; impaired delayed cutaneous hypersensitivity, lymphocyte proliferation response to mitogens, complement activity and secondary response to antigens. There is also a reduced number of rosetting T lymphocytes, increased deoxynucleotidyl transferase activity, decreased serum thymic factor, fewer helper T cells, impaired production of interferon gamma and interleukins 1 and 2, reduced antibody affinity, impaired secretory immunoglobulin A (IgA) antibody response and phagocyte dysfunction. The proportion of helper/inducer T lymphocytes recognized by the presence of CD4 positive antigen on the cell surface is markedly decreased. The ratio CD4/CD8 is significantly decreased. Lymphoid atrophy is a prominent feature of nutritional deprivation. Serum antibody responses are generally intact in PCM. Most complement components are decreased, especially C3, C5, factor B and total hemolytic activity (37-43).
“Nutritional problems have been a part of the clinical aspects of AIDS from its earliest recognition as a new disease” (37,41). “In fact, in many AIDS patients, death seams to be determined more by the individual’s nutritional status than by any particular opportunistic infection. This is, when wasting of lean body mass approaches 55% of normal for age, sex, and height, death is imminent regardless of the forces resulting is such profound malnutrition” (37,41). Furthermore, the severity of the clinical manifestations of AIDS is proportional to the degree of the nutritional deficiencies (44-47).
“Macronutients are related to wasting and energy balance in HIV-infected patients, while micronutrients play different roles in immune function” (48).
In addition to supporting optimal function of the immune system, nutrition is especially critical in children, as it provides the best opportunity for normal growth and development (49,50).
“All persons with HIV infection should be screened for nutritional problems and concerns at the time of their first contact with a health care professional, and routine monitoring should be performed on an ongoing basis” (49).
Scientific evidence strongly suggests that nutritional and antioxidant deficiencies are a requisite prior to both reacting positively on the tests for HIV (ELISA, Western blot, Viral Load) (51-54) and for progressing to AIDS (55,56).
3. NUTRITIONAL DEFICIENCIES AND THE PROGRESSION OF HIV-POSITIVE INDIVIDUALS TO AIDS.
An optimal nutritional status as well as adequate vitamin levels are known to be by themselves enough to prevent the development of AIDS in people who react positively on the tests for HIV (57-64).
For example, regarding vitamins in HIV disease progression and vertical transmission, researchers from the Harvard School of Public Health state: “The higher rates of HIV progression and vertical transmission in developing countries coincide with similarly higher rates of malnutrition and vitamin deficiencies, indicating that HIV infection, may be modified by nutritional status.” “Numerous observational studies report inverse association between vitamin status, measured bio-chemically or as levels of dietary intake, and the risk of disease progression or vertical transmission.” “Adequate vitamin status may also reduce vertical transmission through the intra-partum and breastfeeding routes by reducing HIV viral load in lower genital secretions and breast milk,” and “Vitamin supplements may be one of the few potential treatments that are inexpensive enough to be made available to HIV-infected persons in developing countries” (65).
Macronutrient (carbohydrates, proteins, fat, and fiber) deficiencies have been associated with low CD4 cell counts in HIV-positive individuals. HIV-positive individuals with low mean weight and low arm and muscle circumference (48,66) and HIV-positive children with growth impairment were shown to have low CD4 cell counts (48,67).
Wasting, particularly loss of lean body mass, is associated with early mortality (68,69) and susceptibility to opportunistic infections (48,69). In a case control study nested within a follow up study, HIV-positive IV drug users with wasting (more than 10% loss of weight from baseline to last visit before death; mean follow-up, 2.4 years) had an approximately 8 fold higher risk of mortality compared with controls, after adjusting for CD4 cell counts (48,55).
Higher mortality has been associated with low serum albumin (48,70). Low lean body mass index and high plasma levels of C-reactive proteins were also significant predictors of mortality among HIV-positive individuals followed for 42 months (48,71). Serum albumin and hemoglobin levels are also predictors of prognosis in HIV-positive children (48,72). Micronutrient deficiencies in HIV-positive individuals are associated with faster progression to AIDS (73).
A growing number of scientific trials implicate low serum vitamin A levels as a risk factor for HIV-positive individuals to progress into the clinical manifestations of AIDS (74-86).
“The risk of death among HIV-infected subjects with adequate serum vitamin A levels was 78% less, when compared with Vitamin A-deficient subjects” (65,78).
“In a study carried out among HIV-positive homosexual men, development of Vitamin A deficiency over an 18-month period was associated with a decline in CD4 cell count, widely used as a marker of HIV immune impairment. Normalization of vitamin A was associated with higher CD4 cell counts” (55,65).
“Lower serum levels of vitamin A were associated with a faster rate of progression among men who participated in the Multicenter AIDS Cohort Study (MACS)” (60,65).
In a nested case-control study, HIV-positive individuals with vitamin A deficiency had a fourfold higher risk of death than controls after adjusting for CD4 cell counts (48,55).
In a longitudinal study among HIV-positive IV drug users in Baltimore, low serum retinal levels were associated with a fourfold increase in risk for mortality after adjusting for CD4 cells counts (48,54).
In Rwanda higher likelihood of survival was noted among HIV-positive women with higher serum retinol levels (48,87).
On the other hand: “Among well nourished HIV seropositive men who participated in the San Francisco Men’s Health Study, high energy-adjusted vitamin A intake at baseline was associated with higher CD4 cell count at baseline, as well as with lower risk of developing AIDS during the 6 year period follow up” (62,65).
Development of vitamin A or B12 deficiency was significantly associated with a decline in CD4 cell count in a longitudinal study in HIV-positive gay men (48,88). In the same study, normalization of vitamin A, vitamin B12, and zinc was significantly associated with higher CD4 cell count, a finding that was not affected by the use of AZT.
In a randomized trial, daily supplementation with 180 mg of beta-carotene for 4 weeks was associated with a small increase in total white blood cell count, an increase in CD4 cell count, and a beneficial change in CD4/CD8 ratio compared with study participants receiving a placebo. These parameters decreased when participants in the beta-carotene arm were switched to the placebo arm (48,89).
Daily supplementation with selenium or beta-carotene for 1 year led to significant increases in glutathion peroxidase activity at 3 and 6 months among HIV-positive men and women in France (48,90).
In Thailand, HIV-positive pregnant women in the first trimester with CD4 counts less than 200 cells/cubic mm had mean serum vitamin A beta-carotene levels 37% lower than those in HIV-negative individuals (48,91).
In a longitudinal study in Miami, HIV-positive women with CD4 counts less than 200/cubic mm were more likely to have lower levels of plasma selenium and vitamin A an E than men with similar CD4 cell counts (48,92).
In a placebo-controlled trial in South Africa among children born to HIV-positive women, Vitamin A supplements resulted in approximately 50% reduction in diarrheal morbidity and progression to AIDS among HIV-positive children (65,77). Increased number of natural killer cells in HIV-infected children has also been observed following vitamin A supplementation in South Africa (48,93).
In addition to vitamin A, a growing number of studies show that “HIV-positive” individuals are at higher risk of deficiency of vitamins B1, B2, B6, B12, C, D, and E (65,94-101). Furthermore, deficiencies of B-complex vitamins, vitamin C, vitamin E and vitamin D increment the risk of progression of “HIV-positive” individuals to AIDS (65,94-101). For example, Vitamin B6 deficiency in “HIV-positive” individuals has been associated with reduced natural killer cell cytotoxicity and impaired mitogen-induced lymphocyte proliferation (102).
In a randomized, placebo-controlled, double-blind study in Canada, a significant reduction in viral load was achieved after 3 months of supplementation with large daily doses of vitamins C and E (48,103).
In the MACS study (104) and in a study in San Francisco (105), high levels of vitamin C, thiamin, or niacin intake were associated with a reduced risk of progression to AIDS (48).
Also in the MACS study, high dietary intake of vitamins B1, B2, B6, and niacin were associated with increased survival time of up to 1.3 years (48,106).
Increase intake of iron, vitamin E, and riboflavin significantly reduced the hazard for AIDS (48,105).
Lower vitamin E levels increased the risk of progression to AIDS (48,107). In the same study population, low serum vitamin B12 levels were associated with a twofold increase in the risk for progression (48,108).
Plasma zinc and magnesium levels were shown to be significant predictors of CD4 cell count among HIV-positive individuals in the United States (48,109).
In San Francisco, higher dietary intake of zinc, thiamine, niacin, and riboflavin were positively related to CD4 cell counts (48,105).
In a case-control study nested in the MACS study, patients who progressed to AIDS had significantly lower levels of serum zinc compared with nonprogressors and HIV-negative participants (48,110).
Selenium deficiency in HIV-positive individuals has been observed to increase risk of death among adults (48,111,112).
4. NUTRITIONAL DEFICIENCIES AND THE “TRANSMISSION” OF HIV/AIDS.
Several studies show that vitamin A deficiency is more prevalent among HIV-positive persons compared with HIV-negative individuals (45,56,58,76,83).
Low levels of vitamin A and carotenoid were found to be a risk factor for reacting positively on HIV tests in Pune, India (113), for seroconversion among Kenyan men with genital ulcers (114), and for seroconversion among Rwandan women (115).
There have been several trials concerning the role of vitamin A and carotenoid deficiencies in mother to child transmission of HIV/AIDS (MTCT) during pregnancy, delivery, and breastfeeding (116-133):
In Tanzania for example: “Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1 infected women” (116,117).
“A growing body of data suggests that low serum levels of vitamin A among HIV-infected pregnant women is associated with higher risk of vertical transmission of HIV” (65).
“Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants was lower than that in 264 mothers who did not transmit HIV to their infants” (121).
“In Malawi, higher serum retinol of HIV-infected pregnant women was associated with a reduced risk of vertical transmission” (65,121).
“In Rwanda, low levels of serum vitamin A among HIV-infected women were associated with increased risk of infant death or perinatal HIV-transmission (134).
“Women who had increasing serum retinol levels over time, however, were at a lower risk, whereas women who had declining serum retinol were at a higher risk of transmitting the virus” (65,133).
“Vitamin A supplementation to a population of HIV-infected pregnant women, many of whom had low vitamin A levels, was associated with a decreased number of preterm births and with reduced mother-to-child transmission of HIV in preterm babies, but was not associated with a reduction in HIV transmission overall. Vitamin A decreased HIV transmission in the preterm babies by 47%” (124).
“Detection of vaginal HIV-1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency” (125).
“Women with CD4 cell depletion, especially those with vitamin A deficiency, may be at increased risk of transmitting HIV-1 to their infants through breast milk” (132).
“Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women” in the United States (120).
“In Kenya, low plasma vitamin levels were associated with higher risk of viral shedding in breast milk among HIV-infected women during pregnancy. These results suggest that maternal vitamin A status before and after delivery is an important factor for breast milk transmission of HIV” (48,135).
“Low serum levels of vitamin A and subclinical mastitis in women in Malawi (136) and South Africa (137) have been associated with high viral load in breast milk and an increased risk of HIV transmission through breast milk” (48).
Scientific studies support, therefore, the contention that the use of vitamins by themselves, especially vitamin A, could be enough to avoid what is known as transmission of HIV from person to person, and from mother to child during pregnancy, delivery, and breastfeeding (65,113-133). If this is the case, as many clinical trials and scientific papers contend, supplementation with antioxidant vitamins such as vitamin A and carotenoids constitute an effective, inexpensive and non-toxic practice for African countries.
5. REACTIVITY ON TESTS FOR HIV IN SUB-SAHARAN AFRICA NOT EXPLAINED BY SEXUAL OR VERTICAL TRANSMISSION.
Recently, researchers from Emory University in Atlanta and from Albert Einstein College of Medicine in New York City, after a comprehensive review concluded: “An expanding body of evidence challenges the conventional hypothesis that sexual transmission is responsible for more than 90% of adult HIV infections in Africa. Differences in epidemic trajectories across Africa do not correspond to differences in sexual behavior. Studies among African couples find low rates of heterosexual transmission, as in developed countries. Many studies report HIV infections in African adults with no sexual exposure to HIV and in children with HIV-negative mothers. Unexplained high rates of HIV incidence have been observed in African women during antenatal and postpartum periods” (138).
Researchers state: “By the end of the 1980s, a consensus emerged among AIDS experts dealing with Africa that over 90% of adult HIV infections in sub-Saharan Africa were acquired through heterosexual contact and less than 2% through unsafe injections [139-142]. Unfortunately, this consensus was achieved without research to address confound between sexual and medical exposures” (138).
The very similar frequency of AIDS in both genders in Africa has been blamed by HIV/AIDS researchers and institutions on sexual promiscuity. However, in one model “Anderson and colleagues assumed a mean rate of annual partner change of 3.5 . In contrast, surveys in 12 African countries show unweighted averages of 74% of men and 91% of women aged 15-49 years with no non-regular sex partners in the past year, and only 3.7% of men and 0.7% of women with more than four non-regular partners ” (138).
Empiric data show that promiscuity is, rather, a matter in developed countries: “A survey in Denmark found that 19% of adults aged 18-59 years reported more than one sex partner in the past year ; a survey in France found 17% of men and 7.9% of women aged 18-44 years reported more than one sex partner in the past year ; and a survey in the UK found that 17% of men and 8.4% of women aged 16-44 years reported more than one sex partner in the past year ” (138). Despite this, the frequency of AIDS in developed countries is about 11 men to 1 woman.
“A Zambian study that sequenced viruses to determine epidemiological linkage reported at least 13% of sequences in newly infected persons were not related to their partner’s HIV” (138).
“A study in Zimbabwe in the 1990s found 2.1% HIV prevalence among 933 women with no sexual experience . In a 1988 study of discordant couples in Rwanda, 15 of 25 HIV-positive women with HIV-negative partners reported only one lifetime sex partner . In a 1990 study of teenagers in Uganda, 6.9% of women with no sex partners in the last five years were HIV-positive vs 23% for those with one or more partners; for men, 1% with no partners in the last five years were HIV-positive vs 2.5% of those reporting partners . Among young adults 15-24 years old in Tanzania, a 1995 study found HIV prevalence of 5.6% among men and 3.6% among women who did not report any lifetime sexual activity vs 4.8% and 12% for men and women reporting one or more sexual partners . In a 1999 study in South Africa, 6.8% of women and 1.2% of men 14-24 years old reported never having sex were HIV positive; however, a validation study found some under-reporting of sexual activity . In a case-control study in Uganda, in two of seven cases with only one lifetime sexual partner, the partner was HIV-negative, three were HIV-positive, and two others not tested ” (138).
About a fifth of HIV-positive children in Africa have HIV-negative mothers: “A study in Kinshasha in 1985 found 39% (16 of 44) of HIV-positive inpatient and outpatient children 1-24 months old to have HIV-negative mothers; only five of 16 had been transfused . A study in Rwanda in 1984-86 found 20% (15 of 76) of children 1-48 months old with AIDS or AIDS related complex had HIV-negative mothers; only 15 children had been transfused . In a later report from Rwanda, 7.3% (54 of 704) of mothers of children with AIDS were HIV-negative; transfusions were identified as a risk factor for 22 of the 54 children . Of 26 children less than 15 years old admitted to Uganda Cancer institute with Kaposi’s sarcoma during 1989-94 for which the mother was tested for HIV, 19% (5 of 26) had HIV-negative mothers . A study in Burkina Faso in 1989-90 found 23% (11 0f 48) of HIV-positive children to have HIV-negative mothers . In a 1994 report from Cote d’Ivoire, De Cock and colleagues report that 21% (3 of 14) of children with HIV-1 had mothers without HIV-1, and one of two with HIV-2 had a mother without HIV-2 ” (138).
“HIV incidence during antenatal and/or post-partum periods exceeded what could be expected solely from sexual transmission” (138,161-171). “In one of the seven studies of antenatal and post-partum women , 30 of 634 women had HIV positive partners; three of these 30 women seroconverted in a year” (138,171). “HIV prevalence in African men is generally lower than in women, and many infected men are partnered with infected women. In eight studies of African couples with HIV in one or both partners [150,172-178], the average percent of women with HIV was more than double the percent without HIV who had HIV-positive partners” (138). The high prevalence of HIV reactivity in women during antenatal or post-partum periods “suggests that something more than simply heterosexual transmission is involved” (138). “Whatever happens during one or two pregnancies and post-partum periods – whether iatrogenic or sexual or something else – may largely account for observed high levels of HIV among low risk women in at least some African communities” (138).
“The recognition that significant proportions of HIV in African adults and children cannot be explained on the basis of current knowledge about sexual and vertical transmission” allowed the researchers from Emory University and Albert Einstein College of Medicine to postulate a hypothesis of “iatrogenic transmission” through medical instruments such as syringes and injections (138).
At this point it is important to remember that there are several publications seriously criticizing the accuracy of tests currently used to diagnose HIV infection (179-184).
Long ago, HIV researchers were aware of the lack of specificity of the HIV antibody tests, especially in countries in Africa where “reactivity may be affected when subjects have dad recurrent malaria and other parasitic diseases [perhaps because of autoantibodies involving antigens in the lymphocyte cell line used to grow the virua]  or previous pregnancies [perhaps because of antibodies to DR4 or other HLA types] [186-188]” (189). The US researcher insisted that: “Since the reliability of ELISA test for the measurement of HTLV-III/LAV antibody in Africa sera has been questioned, the extent of this problem remains uncertain” (189). Speaking about the seroepidemiology in Central African countries, a British immunologist states: “It now appears that some of the results obtained were false positives” (190).
Mann also knew that tests for HIV often wrongly identify antibodies to HIV in blood samples (191). “False positives can also occur, if, for example, the frozen blood has thawed and then been refrozen. To make the situation even more complex, many Africans probably have relatively high levels of antibodies, proteins that signal the body’s attempt to fight disease, in their blood, as a result of having other infections, such as malaria. These numerous antibodies tend to bond to one another and cause blood samples to become sticky, which may lead to false positive results” (191).
“Results in serological surveys for antibodies against HIV in Africa were initially distorted by a high false-positive rate” (192).
It is amazing to note that public health officials also know that “serologic studies of HIV in Africa have been inconsistent because of problems in interpretation of the results from ELISA and Western blot tests of banked specimens, particularly from malaria endemic areas, and the validity of these data has been questioned” (193).
Currently, pharmaceutical companies that make and commercialize the kits for HIV tests acknowledge the inaccuracy of these tests. Accordingly, the inserts that come with the kits typically state the following: “Elisa testing alone cannot be used to diagnose AIDS, even if the recommended investigation of reactive specimens suggests a high probability that the antibody to HIV-1 is present” (194). The insert for one of the kits for administering the Western blot warns: “Do not use this kit as the sole basis of diagnosis of HIV-1 infection” (195). The insert that comes with a popular kit to run viral load warns: “The amplicor HIV-1 monitor test, version 1.5, is not intended to be used as a screening test for blood or blood products for HIV or as a diagnostic test to confirm the presence of HIV infection” (196). Abbott goes even farther when it warns: “At present there is no recognized standard for establishing the presence or absence of antibodies to HIV-1 and HIV-2 in human blood” (194).
There are abundant scientific publications explaining that there are more than 70 different documented conditions that can cause the antibody tests to react positive without an HIV infection (179-184). Some of the conditions that cause false positives on HIV tests are: past or present infection with a variety of bacteria, parasites, viruses, and fungi including tuberculosis, malaria, leishmaniasis, influenza, common cold, leprosy and history of sexually transmitted diseases; the presence of polyspecific antibodies, hypergammaglobulinemias, the presence of autoantibodies against a variety of cells and tissues, vaccination, and the administration of gamma globulins or immunoglobulins; the presence of autoimmune diseases like erythematous lupus, sclerodermia, dermatomyositis and rheumatoid arthriris; the existence of pregnancy and multiparity; a history of rectal insemination; addiction to recreational drugs; several kidney diseases, renal failure and hemodialysis; a history of organ transplantation; presence of a variety of tumors and cancer chemotherapy; many liver diseases including alcoholic liver disease; hemophilia, blood transfusions and administration of coagulation factor; even the simple condition of aging, to mention just a few of the conditions (182-184). Interestingly, most of these conditions are common to the African scenario.
The above considerations permit the proposition that reacting positively on tests for HIV is caused by multiple, repeated, and chronic exposure to chemical, physical, biological, mental, and nutritional stressor agents (184). One of the first consequences of poverty is malnutrition, making individuals susceptible to infectious and parasitic diseases, which in turn stimulate the production of polyspecific antibodies, many of which are being detected by HIV tests.
Many are attempting to explain that the current morbidity and mortality of African communities are a consequence of HIV infections. However, it is possible that reacting positively on the so-called tests for HIV in Africa is a result of chronic exposure to poverty and its consequences, such as malnutrition, infections, and parasites (184).
6. OXIDATIVE STRESS AND HIV/AIDS.
Moreover, since the beginning of the AIDS epidemic, free radicals and specifically oxidizing agents have been implicated in the pathogenesis of the new syndrome (197,198). There have been international meetings concerning the role of oxygen free radicals in HIV/AIDS (199,200).
There is today a growing number of scientific publications indicating that oxidizing stress is an absolute requisite for both testing positive on the tests for HIV (201-207) and for developing the clinical manifestations of AIDS (208-230).
Free radical reactions of special significance to immunological phenomena are, for example, the many oxidizing agents that can abstract a hydrogen atom from thiol groups to form thiol radicals (231-233). Thiol groups are important for enzyme activities, receptor functions, disulphite links in immunoglobulins, and T cell activation and proliferation. The super oxide anion radical can react with nitric oxide, resulting in loss of endothelium-derived relaxing factor activity, which is important in the inflammation/disinflammation process. Methionine oxidation can cause protein damage with subsequent changes in immunogenicity. Proteolysis can be increased by free radical damage. The per oxidation of lipids by reactive free radicals produce many biological modulators such as, for example, the 4-hydroxy-alkelans, which produces strong chemotactic activity for phagocytes, alters the adenyl cyclasa system, increases capillary permeability, and alters lymphocyte activation. Lipid hydroperoxides, also from per oxidation of lipids, alter lymphocyte activation. Conditions favoring lipid per oxidation may result in chemo taxis of leukocytes, protein modification, immune complex injury, and cell death (231-233).
Free radicals are produced throughout 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 a disease process (231-233). It is critical for optimal immune responses that there be a balance between free radical generation and antioxidant protection. During phagocytosis by polymorphonuclear leukocytes, for example, super oxide anion radicals are released. These oxygen free radicals can oxidize thiol groups to thiol radicals, and can stimulate lipid per oxidation with the formation of H2O2, which is highly significant in the mechanisms of cell injury. Oxygen free radicals produced during phagocytosis of immune complexes are associated with injury to immune complexes (231-233).
It has often been proposed that free radicals and specifically oxidizing species play important roles in the pathogenesis of AIDS (189-200,234-236).
The above are the scientific fundamentals for the use of antioxidants such as vitamin A and carotenoids, vitamin C, vitamin E, selenium, n-acetyl cisteine, l-gluthamin, zinc, cooper, manganese, alphalipoic acid, coenzyme Q10, and flavonoids or vitamin P, as supplementation for the prevention and treatment of AIDS (48,188-236).
7. NUTRITIONAL AND ANTIOXIDANT DEFICIENCIES AND THE PATHOGENESIS OF HIV/AIDS.
African countries have a high incidence of malnutrition, vitamin deficiencies, and anemia, as well as bacterial, viral, fungal, and parasitic infections and infestations.
For any infectious or parasitic disease to start, it is always a requisite that the host suffer immunodeficiency (237). At the same time, infectious and parasitic diseases themselves cause additional immune suppression and more malnutrition (238,239). This immune suppression is secondary to the accumulation of free radicals, especially oxidizing species, that occurs during and after infectious and parasitic diseases (232,240).
Therefore, in African countries there is a persistent circular occurrence; poverty, malnutrition, immune suppression, infectious and parasitic diseases, more immune suppression, and more malnutrition (241,242).
On the other hand, there is growing scientific data showing that many chronic diseases of adulthood have their origin at “in utero programming” (243-246). This includes illnesses such as coronary heart disease and stroke, hypertension, type II diabetes and other endocrine alterations (243-248), as well as several immunological disturbances (249-259). Therefore, it appears that whatever happens during embryonic and fetal times will be remembered by cells, tissues, organs, and systems throughout a lifetime.
“Research in Gambia associated season of birth with infectious disease mortality after the age of 15 years, suggesting an association between prenatal undernutrition, immune function, and adult vulnerability to infectious disease” (255,259). Prenatal undernutrition has been found to impair antibody responses to vaccination with Salmonella thyfi that last at least up to adolescent times (253). The findings of these researchers “suggest a role for fetal and early infant experience in programming the immune system” which may accompany the individual during its entire life (252,253).
It is scientifically known that prenatal undernutrition alters several aspects of cell-mediated immunity, causes involution of lymphoid tissues such as the thymus, and suppression of antibody responses to vaccination. These deficits persist for weeks or, in some cases, even years (249-259).
In addition, “murine models have documented impairments in immunity after maternal undernutrition that last through adulthood and into the next generation, despite ad libitum feeding of both F1 and F2 generations” (260). Also in mice, deprivation of zinc during pregnancy causes immunodeficiency that can last at least for three generations (261).
It is therefore very probable that in Africa the consequences of poverty and malnutrition are being transmitted from generation to generation with a cumulative effect and that AIDS in Africa may be the topmost consequence of these cumulative effects of poverty.
In this light, the crucial role of maternal undernutrition in the pathogenesis of pediatric AIDS has to be seriously considered to be the case in developing countries (262,263). This reasoning also indicates that malnutrition constitutes the main risk factor for AIDS in adults in developing countries (262,263). Scientifically speaking, there is no rational for indicting sexual promiscuity as the cause of AIDS in Africa, while underestimating the role of poverty, malnutrition, infections and parasites.
8. NUTRITIONAL AND ANTIOXIDANT THERAPY FOR THE PREVENTION AND TREATMENT OF AIDS.
“It is not surprising, therefore, that dietary therapy for AIDS has been proposed, debated, and more importantly surreptitiously or overtly used from the early days of the epidemic” (41).
Twenty years later, researchers insist: “Because nutrient deficiencies may play an important role in the pathogenesis of HIV disease, medical nutrition therapy and counseling are critical aspects of treatment” (49). Nutritional (264-286) and antioxidant (287-305) therapy is then a must in preventing and treating AIDS.
“Supplementation of several amino acids has been suggested as a method for reducing weight loss among HIV-infected individuals. A combination of three amino acids known as HMB/Gln/Arg-beta-hydroxy-beta-methylbityrate (HMB), a metabolite of leucine, L-glutamine (Gln), and L-arginine (Arg), given for 8 weeks to patients with HIV-associated wasting, resulted in significant weight gain for patients in the treatment arm compared with those receiving placebo ” (48).
Clinical trials have identified in detail the vitamin and mineral needs of HIV-positive persons and those with AIDS. These studies suggest the need for increasing the intake of the micronutrients vitamin A and carotenoids, vitamin C, vitamin E, selenium, n-acetyl cisteine, l-gluthamin, zinc, cooper, manganese, alphalipoic acid, coenzyme Q10, flavonoids or vitamin P, and B-complex vitamins as supplementation for the prevention and treatment of AIDS (34-56,197-236,264-305).
When providing Vitamin A as a supplement its potential teratogenic property (307) should be kept in mind. In this regard, the World Health Organization recommends that pregnant women should not take more than 10,000 IU of Vitamin A per day (65).
If we really want to prevent and treat AIDS in Africa, it is an absolute requisite to provide at least the minimum food needs to HIV-positive individuals, to AIDS patients, as well as to all African communities.
A diet providing adequate sources of macronutrients, vitamins, minerals, and antioxidants would have lots of fruits especially papaya, mango, kiwi, pineapple, avocado, bananas, and dry fruits, as well as vegetables, legumes and alga. Use few animal products. Prefer white fatty fish, sheep and goat meat. Prefer sea salt. Use 60-80% fresh, whole, raw organic food. Use garlic, onions, asparagus, beets, cabbage, broccoli, cauliflower, Brussels sprouts, carrots, yeast, whet, and pollen, as well as sprouts, legumes, and cereals. Prefer cold press oils (below 40 degrees Celcius), since this process preserves essential and polyunsaturated fatty acids needed in anti-inflammatory and regenerative processes. Carcamo, sunflower, and olive oils, in this order, are good sources of vitamin F or linoleic acid. Lino oil is a good source of alpha linoleic acid. Eat whole cereals in any manner (rice, barley, wheat, oat). Decrease sugar and candies. Prefer raw organic vegetables and legumes. Drink lots of liquids; water (at least 1.5 litters per day), juices with fresh fruits and vegetables, especially carrots, vegetable broths, and green juices as a source of chlorophyll (for example, blend with water lettuce, spinach, celery, mint, parsley, coriander, and similar foods, and consume without draining). Also, it is very convenient to use bifidogenic foods, for example yogurt and kumis, better made with sheep or goat milk, as well as tofu and miso. Coconut oil is a good source of louric and caprilic acids which are anti candida (271,276,280-286,308).
Some immune stimulant and/or antioxidant herbs (289,293,294,308-311) are; Aloe (Aloe vera), astragalus (Astragalus membranaceus), Siberian ginseng (Eleutherococcus senticosus), Fo-ti (Polygonum multiforum), turmeric (Curuma longa), echinacea (Echinacea angustifolia y E. purpurea), garlic (Allium sativum), licorice or liquorice (Glycyrrhiza glabra), golden seal (Hydrastis Canadensis), cat’s claw (Uncaria tomentosa), ginkgo (Ginkgo biloba), grape fruit seeds (Vitis vinifera), zarzaparrilla or smilax (Smilax officinalis y S. aspera), African potato (Hyposis hemerocallidea/rooperi), and sutherlandia/cancerbush/kankerbos (Sutherlandia frutensces). Sedative and relaxing herbs include; peace flower (Passiflora incarnata), valerian (Valeriana officinalis), chamomile (Matricaria chamomilla), mint (Menta sativa), lavender (Lavanda officinalis), and Siberian ginseng (Eleuterococus senticosus).
There are numerous scientific papers and books that review the issue of nutritional and antioxidant therapy for the prevention and treatment of AIDS (264-315).
A) Nutritional and antioxidant deficiencies have been documented in all patients with AIDS as well as in persons who react positively on “tests for HIV.”
B) Scientific data indicate that nutritional and antioxidant deficiencies are a requisite prior to reacting positively on “tests for HIV.”
C) Nutritional and antioxidant deficiencies are also a requisite of “HIV-positive” individuals prior to the development of the clinical manifestations of AIDS.
D) Reactivity on “tests for HIV” in sub-Saharan Africa cannot be explained by sexual or vertical transmission. It is very probable that reacting positively on the so-called tests for HIV in Africa is a result of chronic exposure to poverty and its consequences, such as malnutrition, infections, and parasites.
E) Nutritional and antioxidant deficiencies play a major role in the pathogenesis of AIDS.
F) Nutritional and Antioxidant supplements are being used successfully in preventing and treating AIDS. An optimal nutritional and antioxidant status can guarantee success in preventing and treating AIDS.
G) Some of the nutritional and antioxidant supplements that have been used in the treatment and prevention of AIDS are; combinations of amino acids, vitamin A and carotenoids, vitamin C, vitamin E, selenium, n-acetyl cisteine, l-gluthamin, zinc, cooper, manganese, alphalipoic acid, coenzyme Q10, B-complex vitamins, and flavonoids or vitamin P.
H) To prevent and treat AIDS in Africa, it is an absolute requisite to provide at least the minimum food needs to HIV-positive individuals, to AIDS patients, and to all African communities. Moreover, diets rich in fresh and organic fruits, vegetables, and cereals, as well as diets rich in bifidogenic foods (yogurt, kumis) are known to be immune stimulants.
Simon J. A physiological essay on the thymus gland. London: Ranshaw; 1845: 100.
Beisel WR. Single nutrients and immunity. Am J Clin Nutr 1982; 35: 417-468.
Beisel WR. The history of nutritional immunology. J Nutr Immunol 1991; 1: 62-78.
Chandra RK. Micronutrients and immune functions, an overview. Ann NY Acad Sci 1990; 587: 9-16.
Chandra RK. Nutrition and Immunity. In: Lachmann PJ et al. Clinical aspects of immunology. Boston: Scientific Publications; 1993: 1325-1338.
Chandra RK. Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in malnourished children. BMJ 1975; 2: 583-585.
Bendich A, Chandra RK. Micronutrients and immune function. New York: New York Academy of Sciences; 1990.
Prabhala RH et al. Immunomodulation in humans caused by beta-carotene and vitamin A. Nutr Res 1990; 10: 1473.
Semba RD. Vitamin A, immunity, and infection. Clin Inf Dis 1994; 19: 489-499.
Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev 1998; 56: S38-S48.
Chandra RK, Au B. Single nutrient deficiency and cell-mediated immune responses. III. Vitamin A. Nutr Res 1981; 1: 181-185.
Anderson R, et al. Vitamin C and cellular immune functions. In: Bendich A, Chandra RK. Micronutrients and immune function. New York: New York Academy of Sciences 1990: 34-48.
Watson RR et al. Effect of beta-carotene on lymphocyte subpopulations in elderly humans: evidence for a dose-response relationship. Am J Clin Nutr 1991; 53: 90-94.
Ross AC, Stephenson CB. Vitamin A and retinoids in antiviral responses. FASEB J 1996; 10: 979-985.
Prabhala RH et al. The effects of 13-cis-retinoic acid and beta-carotene on cellular immunity in humans. Cancer 1997; 67: 1556-1560.
Semba RD et al. Abnormal T-cell proportions in vitamin A-deficient children. Lancet 1993; 341: 5-8.
Bendich A, Shapiro SS. Effects of beta-carotene and canthaxanthin on the immune responses of the rat. J Nutr 1996; 116: 2254-2262.
Semba RD et al. Depressed immune response to tetanus in children with vitamin A deficiency. J Nutr 1992; 122: 101-107.
Coutsoudis A, Kiepiela P, Coovadia H, et al. Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles. Pediatr Infec Dis J 1992; 11: 203-209.
Meydani SN et al. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr 1990; 52: 557-563.
Meydani SN et al. Vitamin E supplementation enhances in vivo immune response in healthy elderly: a dose-response study. JAMA 1997; 277: 1380-1386.
Bendich A. Antioxidant vitamins and immune responses. In: Chandra RK, Alan R. Nutrition and immunology. New York: Liss., Inc., 1988: 125-147.
Hemila H. vitamin C and infectious diseases. In: Pacler L, Fuchs J. Vitamin C in health and disease. New York: Marcel Dekker, 1997.
Meydani SN et al. Vitamin B-6 deficiency impairs interleukin-2 production and lymphocyte proliferation in elderly adults. Am J Clin Nutr 1991; 53: 1275-1280.
Bendich A, Cohen M. B vitamins: effects on specific and non-specific immune responses. In: Chandra RK, Alan R. Nutrition and immunology. New York: Liss, Inc., 1988: 101-123.
Rotruck JT et al. Selenium: biochemical role as a component of glutathione peroxides. Science 1973; 179: 588-590.
Peretz A et al. Effects of selenium supplementation in immune parameters in gut failure patients on home potential nutrition. Nutrition 1991; 7: 215-221.
Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Nutr 1998; 68: 447S-463S.
Black RE. Therapeutic and preventive effects of zinc on serious chilhood infectious diseases in developing countries. Am J Nutr 1998; 68: 476S-479S.
Chandra RK. Fetal malnutrition and postnatal inmunocompetence. Am J Dis Chil 1975; 125: 450-455.
Chandra RK. Interactions between early nutrition and the immune system. In: Barker DJL, Whelan J. The childhood environment and adult disease. Siba Foundation Symposium # 156. London: Wiley; 1991: 77-88.
Gurr MI. The role of lipids in the regulation of the immune system. Prog Lip Res 1983; 22: 257-287.
Jacob RA, et al. Immunocompetence and oxidant defense during ascarbate depletion of healthy men. Am J Clin Nutr 1991; 54: 1302s-1309s.
Jain VK, Chandra RD. Does nutritional deficiency predispose to acquired immunodeficiency syndrome? Nutr Res 1984; 4: 537.
Beach RS, Laura PF. Nutrition and the acquired immunodeficiency syndrome. Ann Intern Med 1983; 99: 565-566.
Gray RH. Similarities between AIDS and PCM (Protein Caloric Malnutrition). Amer J Publ Health 1983; 73: 1332.
Keusch GT, Farthing MJG. Nutritional aspects of AIDS. Annu Rev Nutr 1990; 10: 475-501.
Coodley GO. Nutritional deficiency and AIDS. Ann Intern Med 1990; 113: 809.
Bristol-Myers. Malnutrition and the immune response: Focus on cancer and AIDS. Princeton, NJ; 1994; 26.
Raiten DJ. Nutrition and HIV infection: A review and evaluation of the extant knowledge of the relationship between nutrition and HIV infection. FDA Contract No. 223-88-2124; 1990.
Keusch GT, Thea DM. Malnutrition in AIDS. Med Clin NA 1993; 77(4): 795-814.
Beisel WR. AIDS. In: Gershwin ME, German JB, Keen CL. Nutrition and immunology: Principles and practice. Totowa, NJ: Human Press; 2000; 389-402.
Watson RR. Nutrition and AIDS. 2nd Ed. Boca Raton: CRC Press; 2001: 231.
Chelluri L, Jastremski MS. Insidence of malnutrition in patients with acquired immunodeficiency syndrome. Nutr Clin Pract 1989; 4: 16-18.
Coodley GO et al. Micronutrient concentrations in the HIV wasting syndrome. AIDS 1993a; 7: 1595-1600.
Kotler DP et al. Body composition studies in patients with the acquired immunodeficiency syndrome. Am J Clin Nutr 1985; 42: 1255-1265.
Chlebowski RT. Significance of altered nutritional status in acquired immune deficiency syndrome (AIDS). Nutr Cancer 1985; 7: 85-91.
Kiure AK, Msamanga GI, Fawzi WW. Nutrition and HIV infection. In: Essex M, Mboup S, Kanki PJ, Marlink RG, Tlou SD. AIDS in Africa. 2nd edition. New York: Kluwer Academic/Plenum Publishers. 2002: 419-435.
Mahan LK, Escott -Stump S. Medical nutritional therapy for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In: Food, nutrition, and diet therapy. Philadelphia: W.B. Saunders Company. 2000; 889-911.
Heller L. Nutrition support for children with HIV/AIDS. J Am Diet Assoc 1997; 97: 473.
Melchior JC et al. Resting energy expenditure is increased in stable malnourished HIV-infected patients. Am J Clin Nutr 1991; 53: 437-441.
Ehrenpreis Ed et al. Malabsortion and deficiency of vitamin B12 in HIV-infected patients with chronic diarrhea. Dig Dis sci 1994; 39: 2159-2162.
Ward BJ et al. Vitamin A status in HIV infection. Nutr Res 1993; 13: 157-166.
Semba RD et al. Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med 1993; 153: 2149-2154.
Semba RD et al. Vitamin A deficiency and wasting as predictors of mortality in human immunodeficiency virus-infected injection drug users. JID 1995; 171: 1196-1202.
Karter DL et al. Vitamin A deficiency in non-vitamin-supplemented patients with AIDS: a cross-sectional study. J AIDS Hum Retrovirol 1995; 8: 199-203.
Baum MK et al. Micronutrients and HIV-1 disease progression. AIDS 1995; 9: 1051-1056.
Beach RS et al. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 1992; 6: 701-708.
Moseson M et al. The potential role of nutritional factors in the induction of immunologic abnormalities in HIV-positive homosexual men. JAIDS 1989; 2: 235-247.
Tang AM et al. Dietary micronutrient intake and risk progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. Am J Epidemiol 1993; 138: 1-15.
Bogden JD et al. Micronutrients status and human immunodeficiency virus (HIV) infection. Ann NY Acad Sci 1990; 547: 189-195.
Abrams B et al. A prospective study of dietary intake and AIDS in HIV- seropositive homosexual men. JAIDS 1993; 6: 949-958.
Skurnick JH, et al. Micronutrients profiles in HIV-1-infected heterosexual adults. J Acq Immundef Syndr Hum Retrov 1996; 12: 75-83.
Periquet BA et al. Micronutrient level in HIV-1 infected children. AIDS 1995; 9: 887-893.
Fawzi WW, Hunter DJ. Vitamins in HIV disease progression and vertical transmission. Epidemiology 1998; 9: 457-466.
Castelbon K et al. Nutritional status and dietary intakes in human immunodeficiency virus (HIV)-infected outpatients in Abidjan, Cote d’Ivoire, 1995. Eur J Clin Nutr 1997; 51: 81-86.
Johann-Liang R et al. Energy balance, viral burden, insulin-like growth factor-1, interleukin-6, and growth impairment in children infected with HIV. AIDS 2000; 14: 683-690.
Kotler DP et al. Magnitud of body-cell-mass depletion and the timimg of death from wasting in AIDS. Am J Clin Nutr 1989; 50: 444-447.
Wheeler DA et al. Weight loss as predictor of survival and disease progression in HIV-infection. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Def Syndr Huma Retrovirol 1998; 18: 80-85.
Feldman JG et al. Serum Albumin as a predictor of survival in HIV-infected women in the Women’s Interagency HIV study. AIDS 2000; 14: 863-870.
Melchior JC et al. Malnutrition and wasting, immunodeficiency, and chronic inflammation as ondependent predictors of survival in HIV-infected patients. Nutrition 1999; 15: 865-869.
Shearer WT et al. Evaluation of immune survival factors in pediatric HIV-1 infection. Ann NY Acad Sci 2000; 918: 298-312.
Semba RD. Vitamin A and HIV infection. Proc Nutr Soc 1997; 56: 459-569.
Fawzi WW et al. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania. Pediatr Infect Dis J 1999; 18: 127-133.
Tang AM et al. Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS 1997; 11: 613-620.
Ullrich R et al. Serum carotene deficiency in HIV-infected patients. AIDS 1994; 8: 661-665.
Coutsoudis A et al. The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women. Am J Public Health 1995; 85: 1076-1081.
Semba RD et al. Vitamin A deficiency and wasting as predictors of mortality in human immunodeficiency virus-infected injection drug users. JIF 1994; 171: 1196-1202.
Semba RD. Vitamin A and human immunodeficiency virus infection. Proc Nutr Soc 1997; 56: 1-11.
Landesman S. Vitamin A relationships to mortality in HIV disease and effects on HIV infection: recent and late breaking studies. Presented at forum, Lawton Chiles International House, National Institutes of Health, Bethesda, MD, May 16, 1996.
Tang AM et al. Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS 1997; 11: 613-620.
Garewal HS et al. A preliminary trial of beta-carotene in subjects infected with the human immunodeficiency virus. J Nutr 1992; 122: 728-732.
Ullrich R et al. Serum carotene deficiency in HIV-1 infected patients. AIDS 1994; 8: 661-665.
Loya S et al. The carotenoid halocynthiaxanthin: a novel inhibitor of the reverse transcriptase of human immunodeficiency viruses type 1 and type 2. Arch Biochem Biophys 1992; 293: 208-212.
Watson RR et al. Enhanced survival by vitamin A supplentation during retrovirus infection causing murine AIDS. Life Sci 1988; 43: 13-18.
Yang Y et al. Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells. Proc Natl Acad Sci USA 1995; 92: 3051-3055.
Camp WL et al. Serum retinal and HIV-1 RNA viral load in rapid and slow progressors. J Acquir Immune Defic Syndr Hum retroviral 1998; 18: 401-406.
Baum MK et al. Micronutrients and HIV-1 disease progression. AIDS 1995; 9: 1051-1056.
Coodley GO et al. Beta-carotene in HIV infection. J Acquir Immune Defic Syndr 1993; 6: 272-276.
Delmas-Beauvieux MC et al. The enzymatic antioxidant system in blood and glutathione status in HIV-infected patients: effects of supplementation with selenium or beta-carotene. Am J Clin Nutr 1996; 64: 101-107.
Baum MK et al. HIV-1 infection in women is associated with severe nutritional deficiencies. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16: 272-278.
Phuapradit W et al. Serum vitamin A and beta-carotene levels in pregnant women infected with HIV-1. Obstet Gynecol 1996; 87: 564-567.
Hussey G et al. Vitamin A status and supplementation and its effects on immunity in children with AIDS. In: Program and abstracts of the XVII international vitamin A consultative group meeting: 1996, Guatemala City, Guatemala. Washington DC: International Life Sciences Institute: pages 6, 81.
Harakeh S, Jariwalla RJ, Pauling L. Suppression of human immunodeficiency virus replication by ascarbate in chronically and acutely infected cell. Proc Natl Acad Sci U.S.A. 1990; 87: 7245-7249.
Harakeh S et al. Mechanistic aspects of ascarbate inhibition of human immunodeficiency virus. Chemico-biological Interactions 1994; 91: 207-215.
Tang AM et al. Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS 1997; 11: 613-620.
Wang Y et al. Nutritional status and immune responses in mice with murine AIDS are normalized by vitamin E supplementation. J Nutr 1994; 124: 2024-2032.
Wang Y et al. Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS. Immunopharmacol 1995; 29: 225-233.
Tang AM et al. Low serum vitamin B12 concentrations are associated with faster human immunodeficiency virus type 1 (HIV-1) disease progression. J Nutr 1997; 127: 345-351.
Baum MK et al. Association of vitamin B6 status with parameters of immune function in early HIV-1 infection. JAIDS 1991; 4: 1122-1132.
Haug C et al. Subnormal serum concentration of 1,25 -vitamin D in HIV infection: Correlation with degree of immune deficiency and survival. JID 1994; 169: 889-893.
Baum MK et al. Association of vitamin B-6 status with parameters of immune function in early HIV-1 infection. J AIDS 1991; 4: 1122-1132.
Allard JP et al. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects. AIDS 1998; 12: 1653-1659.
Tang AM et al. Dietary micronutrients intake and risk of progression to AIDS in HIV-1-infected homosexual men. Am J Epidemiol 1993; 138: 937-951.
Abrams B et al. A prospective study of dietary intake and AIDS in HIV-seropositive homosexual men J AIDS 1993; 6: 949-958.
Tang AM, Graham NMH, Saah AJ. Effects of micronutrient intake on survival in HIV-1 infection. Am J Epidemiol 1996; 143: 1244-1256.
Tang AM et al. Low serum B-12 concentrations are associated wiuth faster HIV-1 disease progression. J Nutr 1997; 127: 345-351.
Bogden JD et al. Status of selected nutrients and progression of HIV-1 infection. Am J Clin Nutr 2000; 72: 809-815.
Graham NM et al. Relationship of serum cooper and zinc levels to HIV seropositivity and progression to AIDS. J AIDS 1991; 4: 976-980.
Allavena C et al. Relationship of trace elements, immunological markers, and HIV-1 infection progression. Biol Trace Elem Res 1995; 47: 133-138.
Baum MK et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immuno Defic Syndr Hum Retrovirol 1997; 15: 370-374.
Mehendale SM et al. Low carotenoid concentration and the risk of HIV seroconversion in Pune, India. JAIDS 2001; 26: 352-359.
McDonald KS et al. Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers. AIDS 2001; 15: 635-639.
Moore PS et al. Role of nutritional status and weight loss in HIV seroconversion among Rwandan women. JAIDS 1993; 6: 611-616.
Fawzi WW et al. Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania. JAIDS 2000; 23: 246-254.
Fawzi WW et al. Randomized trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 1998; 351: 1477-1482.
Landers DV. 1995 Nutrition and immune function II: Maternal factors influencing transmission. Nutrition in pediatric HIV infection: Setting the research agenda, Bethesda, MD, September 1995.
Stiehm RE. Newborn factors in maternal-infant transmission of pediatric HIV infection. In: Nutrition in pediatric HIV infection: Setting the Research Agenda. Bethesda, MD: NIH, September 1995.
Greenberg BL et al. Vitamin A deficiency and maternal-infant transmission of HIV in two metropolitan areas in the United States. AIDS 1997; 11: 325-332.
Semba RD et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994; 343: 1593-1597.
Phuapradit W et al. Serum vitamin A and betha-carotene levels in pregnant women infected with human immunodeficiency virus-1. Ostet Gynecol 1996; 87: 564-567.
Semba RD et al. Infant mortality and maternal vitamin A deficiency during human immunodeficiency virus infection. Clin Inf Dis 1995; 21: 966-972.
Coutsoudis A et al. Ramdomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. AIDS 1999; 13: 1517-1524.
Lan Y et al. Carotenoid status of pregnant women with and without HIV infection in Malawi. East Afr Med J 1999; 76: 133-137.
Semba RD et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994a; 343: 1593-1597.
Semba RD et al. Maternal vitamin A deficiency and child growth failure during human immunodeficiency virus infection. JAIDS 1997; 14: 219-222.
Coutsoudis A et al. Effect of vitamin A supplementation on viral load in HIV-1 infected pregnant women. JAIDS 1997; 15: 86-87.
John GC et al. Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency. JID 1997; 175: 57-62.
Mostand SB et al. Hormonal concentration, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from cervix and vagina. Lancet 1997; 350: 922-927.
Shah RS et al. Liver stores of vitamin A in human fetuses in relation to gestational age, fetal size and maternal nutritional status. Br J Nutr 1987; 58: 181-189.
Nduati RW et al. Human immunodeficieny virus type-1 infected cells in breast milk: association with immunosuppression and vitamin A deficiency. JID 1995; 172: 1461-1468.
Landesman S. Vitamin A relationships to mortality in HIV disease and effects on HIV infection: recent and late breaking studies. Presented at forum, Lawtom Chiles International House, National Institutes of Health, Bethesda, MD, May 16, 1996.
Graham N et al. Effects of maternal vitamin A deficiency on infant mortality and perinatal HIV transmission. Paper presented at the National Conference on Human Retroviruses and Related Infections: December 12-16, 1993; Baltimore, Maryland, USA.
Mostad SB et akl. Hormonal concentration, vitamin A deficiency, and other risk factors shedding HIV-1 infected cells from cervix and vagina. Lancet 1997; 350: 922-927.
Semba RD et al. HIV load in breast milk, mastitis, and mother-to-child transmission of HIV-1. J Inf Dis 1999; 180: 93-98.
Willumsen JF et al. Subclinical mastitis as a risk factor for mother-infant HIV transmission. Adv Exp Med Biol 2000; 478: 211-223.
Gisselquist D, et al. HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. International J SID & AIDS 2002; 13: 657-666.
Chin J, Sato PA, Mann JM. Projections of HIV infections and AIDS cases to the year 2000. WHO Bull 1990; 68: 1-11.
Mann JM. Heterosexual transmission of HIV: a global view a decade later. Int J STD AIDS 1993; 4: 353-356.
N’Galy B, Ryder RW. Epidemiology of HIV infection in Africa. J Acquir Immune Defic Syndr 1988; 1: 551-558.
Johnson AM, Laga M. Heterosexual transmission of HIV. AIDS 1988; 2 (Suppl 1): S49-S56.
Anderson RM, Gupta S, Ng W. The significance of sexual partner contact networks for the transmission dynamics of HIV. J Acquir Immune Defic Syndr 1990; 3: 417-429.
Carel M et al. Sexual behavior in developing countries: implications for HIV control. AIDS 1995; 9: 1171-1175.
Melbye M, Biggar RJ. Interactions between persons at risk for AIDS and te general population in Denmark. Am J Epidemiol 1992; 135: 593-602.
Spira A et al. AIDS and sexual behavior in France. Nature 1992; 360: 407-409.
Johnson AM et al. Sexual lifestyles and HIV risk. Nature 1992; 360: 410-412.
Fideli US et al. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retrov 2001; 17: 901-910.
Zaba MW et al. Adjusting ante-natal clinic data for improved estimates of HIV prevalence among women in sub-Saharan Africa. AIDS 2000; 14: 2741-2750.
Allen S et al. Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa. BMJ 1992; 304: 1605-1609.
Konde-Lule JK et al. Adolescents, sexual behavior and HIV-1 in rural Rakai district, Uganda. AIDS 1997; 11: 791-799.
Tengia-Kessy A el al. Assessment of behavioral risk factors associated with HIV infection among youth in Moshi rural district, Tanzania. East Afr Med J 1998; 75: 528-532.
Auvert B et al. HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behavior. AIDS 2001; 15: 885-898.
Malamba SS et al. Risk factors for HIV-1 infection in adults in a rural Ugandan community: a case-control study. AIDS 1994; 8: 253-257.
Mann JM et al. Risk factors for immunodeficiency virus seropositivity among children 1-24 months old in Kinshasha, Zaire. Lancet 1986; ii: 654-657.
Lepage P et al. Are medical injections a risk factor for HIV infection in Children? Lancet 1986; ii: 1103-1104.
Commenges D, et al. Estimating the incubation period of pediatric AIDS in Rwanda. AIDS 1992; 6: 1515-15-20.
Zeigler JL, Kotongole-Mbidde E. Kaposi’s sarcoma in childhood: an analysis of 100 cases from Uganda and relationship of HIV infection. Int J Cancer 1996; 65: 200-203.
Prazuck T, et al. HIV infection and severe malnutrition: a clinical epidemiological study in Burkina Faso. AIDS 1993; 7: 103-108.
De Cock KM, et al. Retrospective study of maternal HIVB-1 and HIV-2 infections in child survival in Abidjan, Cote d’Ivoire. BMJ 1994; 308: 441-442.
Taha TE, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998; 12: 1699-1706.
Wawer MJ, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomized community trial. Lancet 1999; 353: 525-535.
Taha TE, et al. Trends of HIV-1 and sexually transmitted diseases among pregnant and postpartum women in urban Malawi. AIDS 1998; 12: 197-203.
Olayinka BA, Obi CL. Symptomatic HIV-infection in infants according to serostatus of mothers during pregnancy. East Afr Med J 1999; 76: 566-570.
UNAIDS. Zimbabwe. Epidemiological Fact Sheet [2000 update]. Geneva: WHO, 2000.
Qolohle DC et al. Serological sreening for sexually transmitted infections in pregnancy; is there any value in re-screening for HIV and syphilis at the time of delivery? Genotourin Med 1995; 71: 65-67.
Datta P, et al. Mother-to-child transmission of human immunodeficiency virus, type 1: report from Nairobi study. J Infect Dis 1994; 170: 1134-1140.
UNAIDS. Kenya. Epidemiological fact sheet [2000 update]. Geneva: WHO, 2000
Leroy V et al. Seroincidence of HIV-1 infection in African women of reproductive age: a prospective cohort study in Kigali, Rwanda, 1988-1992. AIDS 1994; 8: 683-686.
UNAIDS. Rwanda. Epidemiological fact sheet [2000 update]. Geneva: WHO, 2000.
Hira SK et al. Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia. J Pediatr 1990; 117: 421-424.
Senkoro KP et al. HIV incidence and HIV-associated mortality in a cohort of factory workers and their spouses in Tanzania, 1991 through 1996. J Acquir Immune Defic Syndr 2000; 23: 194-202.
Serwadda D, et al. The social dynamics of HIV transmission as reflected through discordant couples in rural Uganda. AIDS 1995; 9: 745-750.
Carpenter LM et al. Rates of HIV-1 transmission within marriage in rural Uganda in relation to HIV sero-status of the partners. AIDS 1999; 13: 1083-1089.
Roth Dl et al. Sexual practices oh HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men. Int J STD AIDS 2001; 12: 181-188.
Ryder RW, Ndilu M, Hassig SE. Heterosexual transmission of HIV-1 among employees and their spouses at two large business in Zaire. AIDS 1990; 4: 725-732.
McKenna St et al. Rapid HIV testing and counselling for voluntary testing in Africa. AIDS 1997; 11(suppl 1): S103-S110.
King B et al. Voluntary confidential testing for couples in Kigali Rwanda [letter]. AIDS 1993; 7: 1393.
Papadopulos-Eleopulos E, Turner V, Papadimitrioy JM. Is a positive western blot proof of HIV infection? Bio/Technology 1993; 11: 696-707.
Papadopulos-Eleopulos E, Turner V, Papadimitrioy JM, Causer D. HIV antibodies: turther questions and plea for clarification. Curr Med Res Opin 1997; 13: 627-634.
Turner V. Do HIV antibody tests prove HIV infection? Continnum (London) 1996; 3: 8-11.
Johnson C. Factors known to cause false-positive HIV antibody test results. Zenger’s Magazine, San Diego, California, September 1996: 8-9.
Johnson C. Is anybody really positive? Continuum (London); April/May 1995.
Giraldo RA, Ellner M, Farber C, et al. 1. The tests used for the diagnosis of “HIV infection” are highly inaccurate. 2. Being “HIV-positive” does not mean that the person is infected with “HIV”. In: 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.
Biggar RJ et al. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet 1985; ii: 520-523.
Kuhnl P, Seidl S, Holzberger G. HLA DR4 antibodies cause positive HTLV-III antibody ELISA results. Lancet 1985; I: 1222-1223.
Weiss SH, Mann DL, Murray C, Papovic M. HLA-DR antibodies and HTLV-III antibody ELISA testing. Lancet 1985; ii: 157.
Hunter JB, Menitove JE. HLA antibodies detected by ELISA HTLV-III antibody kits. Lancet 1985; ii: 397.
Biggar RJ. The AIDS problem in Africa. Lancet 1986; I: 79-83.
Pinching AJ. AIDS in Africa: lessons for us all. J Roy Soc Med 1986; 79: 501-503.
Mann JM. AIDS in Africa. Sci Amer 1987; March 26: 40-43.
Melbye M et al.Evidence for heterosexual transmission and clinical manifestations of human immunodeficiency virus infection and related conditions in Luzaka, Zambia. Lancet 1986; ii: 1113-1115.
Quinn TC, Mann JM, Curran JW, Piot P. AIDS in Africa: anelidemiological paradigm. Science 1986; 234: 955-963.
Abbott Laboratories. Human immunodeficiency virus types 1 and 2: (E. coli, B. megaterium, recombinant antigen) HIVAB HIV-1/HIV-2 (rDNA) EIA. Abbott Laboratories Diagnostic Division.68-0158/R12, December 1996.
Epitope, Organon Teknika. Human immunodeficiency virus type 1 (HIV-1). HIV-1 Western blot kit. PN201-3039 Revision # 6, page 11.
Roche Molecular Systems. Amplicor HIV-1 Monitor test, version 1.5. 58003466-01. August 2002.
Dworkin BM, Rosenthal W, Wormser G, Weiss L. Selenium deficiency in the acquired immuno-deficiency syndrome. J Parenteral Enteral Nutr 1986; 10: 405.
Papadopulos-Eleopulos E. Reappraisal of AIDS – Is the oxidation induced by the risk factor the primary cause? Medical Hypothesis 1988; 25: 151-162.
Favier A. The place of oxygen free radicals in HIV infection. A collection of papers presented at a conference on “The place of oxygen free radicals in HIV infection”, Les Deux Alpex, France, January 1993. Chemico-Biological Interactions 1994; 91: 77-224.
Piette 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.
Fuchs J et al. Oxidative imbalance in HIV infected patients. Med Hypothesis 1991; 36: 60-64.
Shallenberger F. Selective compartmental dominance: An explanation for a nonifectious, 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.
Jarstrand C, Akerlund B. Oxygen radical release by neutrophils of HIV-infected patients. Chemico-Biological Interactions 1994; 91: 141-146.
Salvain B, Mark AW. The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leukocyte Biol 1992; 52: 111.
Baruchel S, Wainberg MA. The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leukocyte Biol 1992; 51: 111-114.
Polkyov VM et al. Superoxide anion production and enzymatic disbalance in peripheral blood cells isolated from HIV-infected children. Free Radic Biol Med 1994; 16: 15-21.
Hommes MJT et al. Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage. Am J Clin Nutr 1991; 54: 311-315.
Passi S. Progressive increase of oxidative stress in advanced human immunodeficiency. Continuum (London) 1998; 5(4): 20-26.
Favier A et al. Antioxidant status and lipid peroxidation in patients infected with HIV. Chemico-Biological Interactions 1994; 91: 165-180.
Fuchs J et al. Oxidative imbalance in HIV infected patients. Med Hypothesis 1991; 36: 60-64.
Lacey CJ et al. Antioxidant-micronutrients and HIV infection. International J STD & AIDS 1996; 7: 485-489.
Javier JJ et al. Antioxidant micronutrients and immune function in HIV-1 infection. FASEB Proc 1990; 4A: 940-945.
Allard VP et al. Oxidative stress and plasma antioxidant micronutrients in humans with HIV infection. Am J Clin Nutr 1998; 67: 143-147.
Revillard JP, Favier AE, Zittoun M. Lipid peroxidation in human immunodeficiency virus infection. J AIDS 1992; 5: 637-638.
Constants J et al. Fatty acids and plasma antioxidants in HIV-positive patients: correlation with nutritional and immunological status. Clinical Biochemistry 1995; 28: 421-426.
Dworkin BM. Selenium deficiency in HIV infection and the aquired immunodeficiency syndrome (AIDS). Chemico-Biological Interactions 1994; 91: 181-186.
Cirelli A et al. Serum selenium concentration and disease progress in patients with HIV infection. Clin Biochem 1991; 24: 211-214.
Schrauzer GN, Sacher J. Selenium in the maintenance and therapy of HIV-infected patients. Chem Biol Inter 1994; 91: 199.
Simon G et al. Effects of glutathione precursors on huma immunodeficiency virus replication. Chemico-Biological Interactions 1994; 91: 217-224.
Staal FJT et al. Intracellular glutathione levels in T-cells subsets decrease in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe Seyler 1989; 370: 101-108.
Buhl R et al. Systemic glutathion deficiency in symptom-free HIV seropositive individuals. Lancet 1989; ii: 1294-1298.
Dorge W, Eck HL, Mihm S. HIV-induced cysteine deficiency and T-cell dysfunction: a rationale for treatment with n-acetyl-cysteine. Immunol Today 1992; 13: 211.
Passi S et al. Study on plasma polyunsaturated fatty acids and vitamin E, and on erythrocyte glutathion peroxidase in highrisk HIV infection categories and AIDS patients. Clin Chem Enzym Comns 1993; 5: 169-177.
Quey B et al. Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral n-acetyl-cysteine. AIDS 1992; 5: 814.
Kalevic T et al. Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester and N-acetyl-cysteine. Proc Natl Acad Sci U.S.A. 1991; 88: 986
Fabris N et al. AIDS, zinc deficiency and thymic hormone failure. JAMA 1988; 259: 839.
Walter R et al. Zinc status in human immunodeficiency virus infection. Life Sci 1990; 47: 1579.
Falutz J et al. Zinc as a cofactor in HIV-induced immunosuppression. JAMA 1988; 259: 2850-2851.
Graham N et al. Relationship of serum cooper and zinc levels to HIV-1 seropositivity and progression to AIDS. JAIDS 1991; 4: 976-980.
Staal FJT et al. Antioxidants inhibit stimulation of HIV transcription. AIDS Res Hum Retroviruses 1993; 9: 299-306.
Kehrer JP. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 1993; 23: 21-48.
Slater TF. Free radicals: formation, detection, reactivity, and citoxicity. In: Lachman PJ, Peters SK, Rosen FS, Walport MJ. Clinical aspects of immunology. Boston: Blackwell Scientific Publications; 1993: 377-393.
Reid L. Oxidative stress and antioxidants. A nutritional perspective. Continuum (London) 1998; 5(3): 52-54.
Papadopulos-Eleopulos E. Looking back on the oxidative stress theory of AIDS. Continuum ( London ) 1998/1999; 5(5): 30-35.
Papadopulos-Eleopulos E, et al. Oxidative stress, HIV and AIDS. Res Immunol 1992; 143: 145-148.
Giraldo RA. Role of free radicals in immunodeficiency. In: Aids and Stressors. Medellín: Impresos Begón; 1997: 72-75.
Peterson PK. Host defense abnormalities predisposing the patient to infection. Amer J Med 1984; 72: 2.
Playfair JHL. Overview: parasitism and immunology. In: Llachmann PJ et al. Clinical aspects of immunology. Boston: Blackwell Scientific Publications; 1993: 1439-1454.
Ware RE, Kline MW. Immunodeficiency secondary to infectious disease. In: Rich RR et al. Clinical immunology: principles & practice. St. Louis: Mosby; 1996: 808-826.
Slater TF. Free radicals mechanisms in tissue injury. Biochem J 1984; 222: 1-15.
Chandra RK. Nutrition, immunity and infection: present knowledge and future directions. Lancet 1983; i: 688-691.
Giraldo RA. Papel de las enfermedades tropicales en el debilitamiento del sistema inmunolígico y en la fisiopatogénesis del sida. In: Sida y agentes estresantes. Medellín: Editorial Universidad de Antioquia; 2002: 37-46.
Barker DJ. In utero programming of chronic disease. Clin Sci (Colch) 1998a; 95: 115-128.
Barker DJ. Fetal and infant origins of adult diseases. London: BMJ Publishing Group; 1992; 343.
Barker DJ. Mothers, babies and diseases in later life. London: BMJ Publishing Group; 1994.
Barker DJ. Mothers, babies & health in later life. 2nd ed. Church Press 1998b; 217.
Naeye RL et al. Relation of poverty and race to birth weight and organ and cell structure in the newborn. Pediat Res 1971; 5: 17 -22.
Leon DA. Fetal growth and adult disease. Eur J Clin Nutr 1998; 52(suppl ): S72-S82.
Chandra RK. Fetal malnutrition and postnatal immunocompetence. Am J Dis Child 1975b; 129: 450-454.
Chandra RK. Serum thymic hormone activity and cell-mediated immunity in healthy neonates, preterm infants, and small-for-gestational age infants. Pediatrics 1981; 67: 407-411.
Ferguson AC. Prolonged impairment of cellular immunity in children with intrauterine growth retardation. J Pediatr 1978; 93: 52-56.
McDade TW et al. Prenatal undernutrition is associated with reduced immune function in adolescence. FASEB 2000; 14: A792 (abs.).
McDade TW et al. Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr 2001a; 74: 543-548.
McDade TW et al. Prenatal undernutrition and postnatal growth are associated with adolescent thymic function. J Nutr 2001b; 131: 1225-1231.
Moore SE et al. Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa. Int J Epidemiol 1999; 28: 1088-1095.
Lewis D, Wilson C. Developmental immunology and the role of host defenses in neonatal susceptibility. In: Remington J, Klein J. Infectious diseases of the fetus and newborn infant. 4th ed. Philadelphia: W.B. Saunders; 1995; 108-139.
Moscatelli P et al. Defective immunocompetence in foetal undernutrition. Helv Paediatr Act 1976; 31: 241-247.
Hasselbachh H et al. Thymus size in infants from birth until 24 months of age evaluated by ultrasound. Acta Radiol 1999; 40: 41-44.
Moore SE et al. Season of birth predicts mortality in rural Gambia. Nature 1997; 338: 434.
Chandra RK. Antibody formation in first and second generation ofspring of nutritional deprived rats. Science 1975c; 190: 289-290.
Beach RS et al. Gestational zinc deprivation in mice: persistence of immunodeficiency for three generations. Science 1982; 281: 469-471.
Giraldo RA. AIDS and Stressors II: A proposal for the pathogenesis of AIDS. In: AIDS and Stressors. 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. Medellín , Colombia : Impresos Begón ; 1997; 97-131.
Steinbrook R. Battling HIV on many fronts. NEJM 1997; 337: 779.
Goldberg B. AIDS. In: Alternative Medicine. The definitive guide. Fife, Washington: Future Medicine Publishing Inc.; 1994: 494-509.
Abrams DI. Alternative therapies. In: Sande MA, Volberding PA. The medical management of AIDS. 6a ed. Filadelfia: W.B. Saunders Company; 1999: 601-612.
Null G. Alternative treatments. In: AIDS: A second opinion. New York: Seven Stories Press; 2002: 487-581.
Badgley L. Healing AIDS naturally: natural therapies for the immune system. Foster City, California: Human energy Press; 1990: 410.
Byrnes S. Overcoming AIDS with natural medicine: A program for recovery. Revised, 2nd edition. Honolulu, Hawaii: Ecclesia Life Mana; 2001: 183.
Chaitow L. The natural way: HIV & AIDS. Your guide to complementary therapies, alternative techniques and conventional treatments. Shaftesbury, UK: Element Books Limited; 1999: 150.
Passi S, De Luca C. Dietetic advice for immunodeficiency. Continuum (London) 1998-1999; 5(5): 43-52.
Ferguson A, Griffin GE. Nutrition and the immune system. In: Garrow JS, James WPT, Ralph A. Human nutrition and dietetics. Edinburgh: Churchill Livingstone; 2000: 747-766.
Embid A. Inmunidad aumentada por incremento de micronutrients. Medicinas Complementarias 1994; No. 35: 172.
Embid A. Inmunoterapia a dosis infinitesimales. Medicinas Complementarias 1995; No. 38: 170.
Gerrior J, Wanke C. Nutrition and Immunodeficiency Syndromes. In: Coulston AM, Rock CL, Monsen ER. Nutrition in the prevention and treatment of disease. San Diego: Academic Press; 2001; 741-750.
Life Sciences Research Office, FASEB. Nutritional therapy and nutrition education in the care and management of AIDS patients. Tentative report, Task Order 7. Washington, DC: Center for Food Safety and Nutrition, FDA, DHHS, 1990.
Tang AM et al. Effects of micronutrients intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol 1996; 143: 1244-1256.
Romeyn M. Nutrition and HIV: A new model for treatment. San Francisco : Jossey -Bass Publishers; 1995: 353.
Young J. HIV and medical nutrition therapy. J Amer Diet Assoc 1997; 97: S161.
Collins CL. Nutrition care in AIDS. Diet Curr 1988; 15: 1.
Fenton M, Silverman E. Medical nutritional therapy for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In: Mahan K, Escott-Stump S. Krause’s Food, nutrition and diet therapy. Philadelphia: W.B. Saunders Company; 2000: 889-911.
Hickson JF. Diet and nutrition for optimal immune function. In: Bahl SM, Hickson JF. Nutritional care for HIV-positive persons: a manual for individuals and their caregivers. Boca Raton: CRC Press; 1995: 1-36.
Fenton M, Silverman E. Medical nutrition therapy for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In: Mahan LK, Escott-Stump S. Food, nutrition, & diet therapy. Philadelphia: W.B. Saunders Company; 2000: 889-911.
American Dietetic Association (ADA). Position of the ADA and the Canadian Dietetic Association: Nutrition intervention in the care of persons with HIV infection. J Am Diet Assoc 1994; 94: 1042.
American Dietetic Association (ADA), HIV/AIDS medical nutrition therapy protocol. Medical nutrition therapy across the continuum of care, 2nd ed. Chicago: ADA, 1998.
Bahl SM, Hickson JF. Nutritional care for HIV-positive persons: A manual for individuals and their caregivers. Boca Raton: CRC Press; 1995: 190.
Bendich A. Role of antioxidants in the maintenance of immune function. In: Frei. Natural antioxidants in human health and disease. (Chapter IV, Immunity and Infection). San Diego: Academic Press; 1994: 447-467.
Bendich A. Antioxidant micronutrients and immunity. In: Roitt IM, Delves PJ. Encyclopedia of immunology. San Diego: Academic Press; 1992: 151-153.
Fishman RHB. Antioxidants and phytotherapy. Lancet 1994: 344: 1356.
Turner VF. Reducing agents and AIDS - Why are we waiting? Med J Austr 1990; 153:502.
Halliwell B, Cross C. Reactive oxygen species, antioxidants and acquired immunodeficiency syndrome. Arch Intern Med 1991; 151: 29-31.
Adam ES. Antioxidant supplementation in HIV/AIDS. Nurse Practit 1995; 20: 8.
Greenspan HC. The role of oxidative oxygen species, antioxidants and phytopharmaceuticals in human immunodeficiency virus activity. Med Hypothesis 1993; 40: 85.
Greenspan HC, Arouma O. Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunol Today 1994; 15: 209.
Greenspan HC, Arouma O. Could oxidative stress initiate programmed cell death in HIV infection? A role for plant derived metabolites having synergistic antioxidant activity. Chemico-Biological Interactions 1994; 91: 187-197.
Tang AM et al. Improved antioxidant status among HIV-infected injecting drug users on potent antiretroviral therapy. JAIDS 2000; 23: 321-326.
Byrnes SC. Staying on top of oxidative stress. Healthy and Natural Journal, Millenium Wellness Guide 1999. firstname.lastname@example.org. Available in http://www.powerhealth.net.
Zhang Z, Inserra PF, Watson RR. Antioxidants and AIDS. In: Garewal HS. Antioxidants and disease prevention. Boca Raton: CRC Press; 1997; 45-66.
Garewal HS. Antioxidants and disease prevention. Boca Raton: CRC Press; 1997: 186.
Sies H. Oxidative stress: oxidants and antioxidants. London: Academic Press; 1991: 507.
Frei B. Natural antioxidants in human health and disease. San Diego: Academic Press; 1994: 588.
CoodleyY GO. Beta-carotene therapy in human immunodeficiency virus infection (Abstract). Clin Res 1991; 29: 634A.
Coodley GO et al. Beta-carotene in HIV infection. JAIDS 1993; 272-276.
Coodley et al. Beta-carotene in HIV infection: an extended evaluation. AIDS 1996; 10: 967-973.
Cathart R. Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS). Med Hypothesis 1984: 14: 423.
Clark RH et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methyl butyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN 2000; 24: 133-139.
Rothman KJ et al. Teratogenicity of high vitamin A intake. NEJM 1995; 333: 1369-1373.
Rogers SA. Man does not live by bread alone: enzymes, juicing, cleansing, flushing and brushing. In: Wellness against all odds. Syracuse, NY: Prestige Publishing; 1994: 110-144.
Schultz V, Hansel R, Tyler VE. Agents that increase resistance to disease: adaptogens; immune stimulants; botanical antioxidants. In: Rational phytotherapy. A physician guide to herbal medicine. Springer; 1998: 269-273, 273-281, 282-286.
Yuan-kun L et al. Modulation of immune responses. In: Handbook of probiotics. New York: John Wiley & Sons, Inc.; 1999: 161-177.
Embid A. El yogur estimula la inmunidad. Medicinas Complementarias 1994; No. 35: 171.
Fields-Gardner C. Human immunodeficiency virus infection. In: Matarese LE, Gottschlich MM. Contemporary nutrition support practice: A clinical guide. Philadelphia: Saunders; 2003: 520-532.
Giraldo RA. An effective alternative for the prevention of AIDS. Internet Discussion during the South African Presidential AIDS Advisory Panel, 2000 http://www.robertogiraldo.com/eng/papers/AnEeffectivePreventionForAIDS.html
Giraldo RA. An effective alternative for the treatment of AIDS. Internet Discussion during the South African Presidential AIDS Advisory Panel, 2000. <http://www.robertogiraldo.com/eng/papers/AnEffectiveTreatmentForAIDS.html
Giraldo RA, Ródenas P, Flores JJ, Embid A. Tratamiento y prevención del sida: guía de principios básicos para una alternativa no tóxica, efectiva y barata. November 2002 http://www.robertogiraldo.com.html
1 Physician, specialist in internal medicine, infectious and tropical diseases. New York. E-mail: RobGiraldo@aol.com Website: www.robertogiraldo.com
Roberto A. Giraldo