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HIV Lecture



Family Name Genus Name Species Name









Origins:









Transmission:

a) List methods by which transmission occurs-



b) List methods by which transmission does not occur (Refer to CDC Website &

“Search- HIV”)





Clinical Outcome of HIV:









Overview of HIV structure and functions: Draw this out!









Life Cycle and explain significance (You Tube Video:

http://www.youtube.com/watch?v=9leO28ydyfU)





1.







2.

3.





4.



5.





6.







7.







8.









Potential Vaccines:

Vaccine attempts-





Future Outlook for vaccines-





Alternative Strategies:





AIDS-









Prions:





Who discovered?







What are prions?

What diseases are prions linked to?





What two forms do prions come in?







In which hosts do prion diseases develop?

ground flaxmeal and/or “All-1” powder added



Lunch and Dinner



Season sardines in water (green and white label), green salad.

*

Swordfish steak, grilled onions, green salad with flax oil dressing.

*

Flank steak, baked potato, green salad with flax oil dressing.

*

Broiled red snapper, steamed broccoli, baked yams.

*

Large mixed green salad w/ oil and lemon juice, small can of tuna, chopped yellow and

sweet red pepper.

*

Flank steak or any meat, green beans with sliced almonds, brazil nuts, green salad with flax

dressing.

*

Broiled mackerel, steamed broccoli, green beans or other vegetable.

*

Beef, lentil and vegetable soup, (celery, carrots, onion, cabbage).

*

Chicken salad made with sugar-free mayonnaise, roasted vegetables, spinach salad.



Snacks

Fresh coconut, roasted garlic or almond butter on rice cake or celery, protein shakes with

freshly ground flaxseeds added, handful of raw almonds, hazelnuts, walnuts, brazil nuts, or

sesame seeds, an organic apple, pear, or grapes, sugar-free yogurt, rice cakes with nut

butter, 1 whole grain muffin with 1 tsp. No sugar added jam, guacamole and fat-free chips,

fresh or dried organic fruit of any kind, 2 oz. Cheese, lean hormone free meat with

mustard, hard boiled egg.

1

Program HIV





Beverages

Green drinks: Green Magma, Kyogreen, or Green Kamut: (1 tsp. 1-3x day in water)

Herbal Teas: Chia Tea, Chamomile, Green Tea with Cinnamon Stick



Avoid

Sugar, alcohol, processed and refined foods, hydrogenated oils, safflower, sunflower,

corn oils, soft drinks



Suggestions And Goals

Drink at least 8 glasses of filtered water per day, engage in activities which will help keep a

positive mental attitude such as meditation, deep breathing, visualization, yoga, and prayer,

get lots of sleep, and exercise regularly (walking, tai chi, stretching).



Studies show that both forms of carnitine are of benefit for HIV patients. 6 grams per day

of carnitine has been shown to deliver benefit to those with AIDS in as little as 14 days.

AIDS patients who take the drug AZT (zidovudine) must take carnitine. AZT depletes

carnitine, causing a serious shortage in cellular energy. The symptoms of AIDS-- muscle

weakness, loss of lean tissue, fatigue, immune deterioration-- mimic the symptoms of

carnitine depletion.

Supplements



Selenium 400 mcg

Acidophilus and Bifidobacteria 1-6 capsules up to 1-3 Tbsp. of each

Vitamin C 1-50 grams (very individual)

Lipoic Acid 100-600 mg

Carnitine (esp. with AZT users) 1,000-3,000 mg (½ hour before meals)

Acetyl-L-carnitine 500-1500 mg

CoQ10 50-300 mg

N-Acetyl-Cysteine 1200-2400 mg

Taurine 1-3,000 mg

Glutamine 1-20 g (especially when diarrhea is present)

Vitamin E 400-800 IUs

Natural mixed carotenoids 50,000-100,000 IUs

Magnesium 400-600 mg in divided doses

Zinc 15-50 mg or as per ZTT

Folic acid and B12 1,000 mcg of each

EPA/DHA 500-3,000 (esp. useful in wasting syndrome)

GLA 240 mg 1-2 per day

Curcuminoids 100-500 mg

Chlorella and/or Spirulina 1-2 tablespoons per day if budget allows

B complex 50 mg

Thymus Polypeptide Extract 2-3 capsules per day

Helpful Herbs Reishi, Self Heal, Avena Sativa, Astragalus

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Program HIV



Research Review



Selenium Deficiency is an Independent Predictor of Survival in HIV

We researched immune parameters and nutrients known to affect immune function were evaluated at 6-

month intervals in 125 HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5 years. Our

results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1

infection.1



Vitamin C and E Reduce Free Radical Levels and Viral Load

Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol

acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. The vitamin

group (n = 26) had an increase in plasma concentrations of alpha-tocopherol and vitamin C and a

reduction in lipid peroxidation measured by breath pentane, plasma lipid peroxides and malondialdehyde

when compared with controls (n = 23). There was also a trend towards a reduction in viral load.

Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction

in viral load..2



Deficiency in antioxidant micronutrients have been observed in patients with AIDS. An increase in free

radical production and lipid peroxidation has been also found in these patients, and takes a great

importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1

replication secondary to free radicals overproduction. In adults we observe a progressive decrease for zinc,

selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II.

However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal

value. N-Acetyl cysteine or ascorbate have been demonstrated in cell culture to be capable of blocking the

expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis

of infected cells. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants.

The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine

seem to be beta-carotene, selenium and zinc.3



Antioxidants such as vitamin E and selenium are important for keeping the virus from becoming more

virulent.4



Patients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium

dysfunction and have increased needs for antioxidants. Taking 100 microg selenium daily and 30 mg beta-

carotene twice daily over the period of one year protected their endothelium.5



Lipoic Acid Inhibits HIV in Cell Culture Study Better than NAC

We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-

stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was

required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was

completely abolished by 1 mM LA. These findings confirm the efficacy of LA as a therapeutic regimen for

HIV infection and acquired immunodeficiency syndrome (AIDS).6



NAC Helps Restore Redox Potential in Cell Culture Study

Primary murine embryonic fibroblasts transfected with HIV-1 TAT demonstrated decreased levels of high

energy phosphates (ATP, GTP, UTP/CTP), adenine nucleotides (ATP, ADP, AMP), and both



3

Program HIV



NAD+/NADH redox pairs, resulting in a substantial loss of redox poise. A greater than 50% decrease in

intracellular reduced glutathione (GSH) concentration was accompanied by the extracellular appearance of

acidic fibroblast growth factor (FGF-1). Addition of either N-acetyl-L-cysteine or glutathione ester (GSE),

but not L-2-oxothiazolidine 4-carboxylate, partially restored intracellular GSH levels and resulted in loss of

extracellular FGF-1. Collectively, these results suggest that HIV-1 TAT induces a condition of oxidative

stress, which mediates cellular secretion of FGF-1, an observation relevant to the pathophysiologic

development and progression of AIDS-associated Kaposi's sarcoma.7



Folic Acid

A total of 25 subjects with HIV were fasted and given 5 mg oral folic acid; blood samples were taken at

time zero and after 30, 60, 90 and 180 min. Absorption of folic acid appears to be significantly impaired in

HIV disease, irrespective of the stage of the disease and notwithstanding gastro-intestinal complaints,

pathogen-negative diarrhea or drug treatment. We here present functional data, complementary to

previously reported structural and biochemical findings, to support the hypothesis that the virus can cause

an enteropathy in the absence of opportunist infection.8



B12

HIV-positive patients frequently have absorption disorders, including vitamin B12 malabsorption. Current

evidence suggests that low vitamin B12 levels are more common as the HIV disease progresses. 9



Magnesium regulates immune function

Magnesium is closely tied to immune function HIV patients. One study demonstrated that the absolute

number of T4-lymphocytes was directly correlated with the serum Mg concentration.10



Zinc

Impaired cellular and humoral immunity and phagocytic function have been attributed to zinc deficiency.

This study examined the association between low serum zinc concentration and opportunistic infections in

hospitalized patients with the acquired immune deficiency syndrome (AIDS). We examined the records

from all 505 inpatient consultations performed by our Nutrition Service from May 1992 through June

1994. Patients with zinc deficiency (LSZ) had a significantly higher incidence of bacterial infection than did

patients with normal zinc. Patients with borderline zinc levels had an intermediate incidence of bacterial

infection. Severe zinc deficiency was noted in 29% and borderline levels in an additional 21% of

hospitalized AIDS patients. Hypozincemia was associated with an increased incidence of concomitant

systemic bacterial infections.11



Elevated Copper is frequently found in HIV

A total of 142 HIV-infected individuals and 84 control subjects were studied. Serum copper levels in

HIV- infected subjects were significantly higher than those found in control individuals.12



Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS

were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up

time 2.5 years). Serum copper levels were higher (p = 0.002) in HIV-1- seropositive progressors than the

seropositive nonprogressors and the seronegatives. Conversely, serum zinc levels were lower (p = 0.016) in

the seropositive progressors than the seropositive nonprogressors and the seronegatives. Furthermore, in

a logistic regression, higher serum copper and lower serum zinc predicted progression to AIDS



4

Program HIV



independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both

nutrients.13



Carnitine

There is an increasing body of evidence that subgroups of patients infected with human immunodeficiency

virus type 1 possess carnitine deficiency. Tissue depletion precipitated by drug toxicities, particularly

zidovudine (AZT), is a major etiology and concern. Carnitine deficiency may impact on energy and lipid

metabolism, causing mitochondrial and immune dysfunction. There are convincing laboratory data

showing the in vitro ameliorative effects of L-carnitine supplementation of zidovudine-induced

myopathies and lymphocyte function. 14



Acetyl-L-Carnitine

We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral

neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues (ddl, ddC,

d4T). Subjects who did not develop peripheral neuropathy while staying on treatment with ddl (n = 10) or

zidovudine (n = 11) served as the control groups. HIV-negative subjects with axonal on demyelinating

autoimmune neuropathies (n = 10) and healthy individuals (n = 13) were additional control groups.

Subjects experiencing axonal peripheral neuropathy on treatment with ddl, ddC and d4T had significantly

reduced levels of acetyl-carnitine in comparison to the control groups. No difference was observed in the

levels of total carnitine between study subjects and the control groups. Our results demonstrate that

subjects who developed peripheral neuropathy while staying on treatment with ddl, ddC and d4T had

acetyl-carnitine deficiency. The critical role of acetyl-carnitine for the metabolism and function of the

peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may

contribute to the neurotoxicity of ddl, ddC and d4T, even though the interference with mitochondrial

DNA synthesis is regarded as the main cause of their toxicity.15



CoQ10

AIDS patients (2 groups) had a blood deficiency (p less than 0.001) of coenzyme Q10 vs. 2 control groups.

AIDS patients had a greater deficiency (p less than 0.01) than ARC patients. ARC patients had a deficiency

(p less than 0.05) vs. control. HIV-infected patients had a deficiency (p less than 0.05) vs. control. The

deficiency of CoQ10 increased with the increased severity of the disease, i.e., from HIV positive (no

symptoms) to ARC (constitutional symptoms, no opportunistic infection or tumor) to AIDS (HIV

infection, opportunistic infection and/or tumor). This deficiency, a decade of data on CoQ10 on the

immune system, on IgG levels, on hematological activity constituted the rationale for treatment with

CoQ10 of 7 patients with AIDS or ARC. One was lost to follow-up; one expired after stopping CoQ10; 5

survived, were symptomatically improved with no opportunistic infection after 4-7 months. In spite of

poor compliance of 5/7 patients, the treatment was very encouraging and at times even striking.16



Glutamine Reduces Intestinal Permeability

Up to 20% of patients with AIDS have abnormal intestinal permeability. Glutamine seems to play an

important role in preventing the increase in intestinal permeability and loss of intestinal mucosal mass

associated with total parenteral nutrition, and may be superior to glucose for oral rehydration in the setting

of intestinal infection. This study was designed to see if supplemental glutamine could alter the abnormal

intestinal permeability of AIDS. Randomly chosen patients with AIDS from the Jacobi Medical Center

human immunodeficiency virus (HIV) clinic underwent intestinal permeability testing using lactulose and

mannitol. Those with abnormal intestinal permeability were enrolled. Duodenal biopsies were performed

with a Crosby capsule and the patients were randomized in a double-blind fashion to receive placebo or

5

Program HIV



glutamine (4 g/day or 8 g/day) for 28 days, after which intestinal permeability tests and duodenal biopsies

were repeated. Intestinal morphology was graded by ratio of villus height to crypt depth, and by degree of

inflammation. All patients complied with the therapy and there were no dropouts or reported side effects.

The results showed less worsening of intestinal permeability with the 4 g/day dose, compared with

placebo. At the 8 g/day dose, there was stabilization of intestinal permeability and improved absorption

of mannitol. Intestinal morphology and inflammation did not change in any group. These results, although

not significant, suggest a trend towards improved intestinal permeability and enhanced intestinal

absorption with glutamine. Glutamine doses of at least 20 g/day may be necessary to improve intestinal

permeability.17



Omega 3 Fats May Help Prevent Weight Loss

Cytokines may be involved in weight loss and disturbances of metabolism associated with human

immunodeficiency virus (HIV) infection. Dietary n- 3 fatty acids reduce the production of interleukin-1

(IL-1) and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) in normal humans

and prevent IL-1 and TNF anorexia in animals. Accordingly, we studied the nutritional and metabolic

effects of a 10- week trial of dietary fish oil (MaxEPA 18 g/day) in men with weight loss due to acquired

immune deficiency syndrome (AIDS). Twenty men were enrolled, and 16 completed the 10-week

supplementation period. Prior weight loss was 13.7 +/- 1.8 kg(17.4 +/- 1.6% body weight, means +/-

SE). The metabolic measurement of de novo hepatic lipogenesis fell and weight was gained (2.1 +/- 1.3

kg) in subjects who did not develop new AIDS-related complications, but further increases in DNL and

further weight loss were observed in subjects who developed a new AIDS complication (p0.05 for

interaction between new complication and change in DNL). No changes in body weight, food intake,

serum triglycerides, serum cytokines, or DNL were observed in the unsupplemented group. We conclude

that fish oil is a weak anticytokine agent that is unable to overcome the metabolic and nutritional

consequences of acute AIDS-related complications but may exert a clinical anticytokine effect in stable

AIDS patients.18



Cell Culture Study Shows Benefit of Extract of Self-Heal (Prunella Vulgaris)

Crude extracts of four Chinese herbs, Arctium lappa, Astragalus membranaceus, Andrographis paniculata,

and Prunella vulgaris (Self-Heal), were assessed in several tissue culture lines for anti-HIV activity and for

cytotoxicity. One extract, obtained from P. vulgaris, was able to significantly inhibit HIV-1 replication with

relatively low cytotoxicity. Pretreatment of uninfected cells with the extract prior to viral exposure did not

prevent HIV-1 infection. By contrast, preincubation of HIV-1 with the purified extract dramatically

decreased infectiousness. These results suggest that the purified extract antagonizes HIV-1 infection of

susceptible cells by preventing viral attachment to the CD4 receptor.19



1. Baum MK, Shor-Posner G, Lai S, et al. High risk of HIV-related mortality is associated with selenium

deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997;15(5):370-4.

2. Allard JP, Aghdassi E, Chau J, et al. Effects of vitamin E and C supplementation on oxidative stress and

viral load in HIV-infected subjects. Aids 1998;12(13):1653-9.

3. Favier A, Sappey C, Leclerc P, Faure P, Micoud M. Antioxidant status and lipid peroxidation in patients

infected with HIV. Chem Biol Interact 1994;91(2-3):165-80.

4. Beck MA, Levander OA. Dietary oxidative stress and the potentiation of viral infection. Annu Rev Nutr

1998;18:93-116.

5. Constans J, Seigneur M, Blann AD, et al. Effect of the antioxidants selenium and beta-carotene on HIV-

related endothelium dysfunction. Thromb Haemost 1998;80(6):1015-7.

6. Merin JP, Matsuyama M, Kira T, Baba M, Okamoto T. Alpha-lipoic acid blocks HIV-1 LTR-dependent

expression of hygromycin resistance in THP-1 stable transformants. FEBS Lett 1996;394(1):9-13.



6

Program HIV



7. Opalenik SR, Ding Q, Mallery SR, Thompson JA. Glutathione depletion associated with the HIV-1

TAT protein mediates the extracellular appearance of acidic fibroblast growth factor. Arch Biochem

Biophys 1998;351(1):17-26.

8. Revell P, O'Doherty MJ, Tang A, Savidge GF. Folic acid absorption in patients infected with the human

immunodeficiency virus. J Intern Med 1991;230(3):227-31.

9. Remacha AF, Cadafalch J. Cobalamin deficiency in patients infected with the human immunodeficiency

virus. Semin Hematol 1999;36(1):75-87.

10. Beck KW, Schramel P, Hedl A, Jager H, Kaboth W. [Trace element concentrations in HIV infected

patients]. Onkologie 1989;12 Suppl 3:43-7.

11. Koch J, Neal EA, Schlott MJ, et al. Zinc levels and infections in hospitalized patients with AIDS.

Nutrition 1996;12(7-8):515-8.

12. Moreno T, Artacho R, Navarro M, Perez A, Ruiz-Lopez MD. Serum copper concentration in HIV-

infection patients and relationships with other biochemical indices. Sci Total Environ 1998;217(1-

2):21-6.

13. Graham NM, Sorensen D, Odaka N, et al. Relationship of serum copper and zinc levels to HIV-1

seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 1991;4(10):976-80.

14. Mintz M. Carnitine in human immunodeficiency virus type 1 infection/acquired immune deficiency

syndrome. J Child Neurol 1995;10 Suppl 2:S40-4.

15. Famularo G, Moretti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with

neurotoxicity on treatment with antiretroviral nucleoside analogues. Aids 1997;11(2):185-90.

16. Folkers K, Langsjoen P, Nara Y, et al. Biochemical deficiencies of coenzyme Q10 in HIV-infection

and exploratory treatment. Biochem Biophys Res Commun 1988;153(2):888-96.

17. Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V. A double-blind placebo-controlled

pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS. Am J

Gastroenterol 1998;93(6):972-5.

18. Hellerstein MK, Wu K, McGrath M, et al. Effects of dietary n-3 fatty acid supplementation in men

with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of

cytokine production. J Acquir Immune Defic Syndr Hum Retrovirol 1996;11(3):258-70.

19. Yao XJ, Wainberg MA, Parniak MA. Mechanism of inhibition of HIV-1 infection in vitro by purified

extract of Prunella vulgaris. Virology 1992;187(1):56-62.









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