Fwd: Can Exercise Help Prevent & Treat AIDS?

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Can Exercise Help Prevent & Treat AIDS?

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Can Exercise Help Prevent & Treat Aids?

 

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Dr. Veljko Velkovic presents evidence on how exercise may

help treat and prevent AIDS, and if so, the simplest, most

widely available and affordable natural 'vaccine' is being

ignored.

 

This article has been posted on the ISIS website

 

www.i-sis.org.uk/CEHPAids.php

 

A fully referenced version of this

report is posted on ISIS member's website.

 

www.i-sis.org.uk/full/CEHPAidsFull.php

 

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can be found at

 

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Introduction

 

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

 

The most effective way to control the HIV/AIDS pandemic

would be the development of a safe and effective HIV

vaccine. Unfortunately, despite enormous scientific and

financial resources being deployed worldwide over the past

15 years, no vaccine candidate is on the immediate horizon

[1,2] (but see " Pink panacea, an AIDS vaccine? " this

series). There are strong indications, besides, that the

AIDS vaccines currently tested in humans are not only

ineffective but also harmful [3-5]. In addition, current

medical therapy of HIV disease is extremely toxic, with

multiple side effects and drug interactions (see " AIDS &

HIV? " this series). It is also very expensive, and carries

risks of developing drug-resistant HIV strains.

 

 

It is clearly desirable to pursue other less toxic,

inexpensive, non-drug approaches in order to slow the spread

of HIV infection and to decrease the burden of HIV infection

and treatment.

 

 

The answer may come from certain antibodies that appear to

be directly involved in controlling HIV disease progression

[6,7]. These antibodies have specific affinity, or cross

reactivity, to the HIV-1 envelope protein (gp120 surface

antigen, residues 280-302, designated peptide NTM); but may

be naturally occurring auto-antibodies (antibodies generated

against the individual's own antigens) against a small

protein molecule that acts to dilate the blood vessels in

the intestine, the vasoactive intestinal peptide (VIP)

[8,9].

 

 

It so happens that aerobic exercise training stimulates the

formation of these anti-VIP/NTM antibodies [10] in both

normal and HIV-positive individuals, and perhaps both could

benefit from such exercise [9].

 

 

Increased levels of anti-VIP/NTM antibodies induced by

exercise may have two beneficial effects. First, in HIV-

negative individuals, the anti-VIP/NTM antibodies could bind

HIV particles in circulation and prevent them from reaching

their target cell, thereby, reducing the risk of infection

with HIV and decrease the transmission of the disease.

Second, in HIV-positive individuals, increased levels of

anti-VIP/NTM could slow HIV disease progression and

reconstitute the damaged immune system.

 

 

Aerobic exercise may be an important, inexpensive, non-

toxic, widely available front line defence and therapy

against HIV/AIDS. By acting as an immune stimulant (for both

HIV positive and HIV negative individuals), it creates a

type of " natural vaccine " that, if widely adopted, could

contribute to a worldwide slow-down of the AIDS pandemic.

 

HIV and AIDS disease

 

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

 

The first step in HIV infection involves the gp 120 on the

outer envelope of the virus binding to receptors on the cell

surface of the host, allowing the HIV virus to enter the

cell. The central portion of the gp120 molecule has an

immunoglobulin-like structure, which facilitates

participation in the immune network. Therefore, immediately

after infection, HIV tries to produce a fit to the host

idiotype (individual type) by producing thousands of

variants of gp120. This process of adaptation usually takes

years, and during this time, the host immune system is more

or less able to control the HIV disease.

 

 

In some HIV-infected persons, this period is short, and in

others it can be quite long, giving rise to the designations

" slow " and " fast " disease progression. After this latent

period, a separate fraction of viruses will be established

whose gp120 carries the host idiotype [11-13]. This

population of HIV becomes accepted by the host immune system

as 'self' and therefore protected from the host's immune

attack. Even worse, these gp120 molecules will be included

in regulation of the immune network, destabilizing its vital

components and accelerating progression of disease [14]. In

this way, HIV may escape from the latent period and

progressively destroy the immune system of the infected

person.

 

 

The gp120 protein represents the key component of all AIDS

vaccine candidates that are currently in clinical trials.

These vaccines may have an important flaw in that they

produce antibodies that neutralize only the HIV variants,

which carry vaccine-like gp120. As the variants of gp120 are

produced by the HIV infection, the vaccine antibodies may

have the effect of disarming the immune system's antiviral

response and thus, increasing the likelihood of rapid

disease progression [1,4,5]. This phenomenon has been seen

in gp120 vaccine volunteers who later became infected with

HIV [15,16], and would certainly reduce the utility of an

HIV vaccine in AIDS prevention.

 

Useful auto-antibodies in HIV disease

 

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

 

If an Achilles' heel exists in HIV, it might be in the

central portion of gp120 (residues 280-302,

RSANFTDNACTIIVQLNESVEIN, designated as peptide NTM [6]).

(The letters stand for different amino acids: R=Arginine,

S=Serine, A=Alanine, N=Asparagine, F=Phenylalanin,

T=Threonine, D=Aspartic acid, C=Cystine, I=Isoleucine

V=Valine, Q=Glutamine, L=Leucine, E=Glutamic acid) This

portion of the molecule is highly conserved in all known HIV

variants and appears to be crucial for viral infectivity. In

fact, researchers have demonstrated that minimal changes in

this sensitive peptide region will completely abolish HIV

infectivity. Unfortunately, this part of gp120 is not

immunogenic in humans [17] because the immune system treats

this part of gp120 as 'self', possibly due to peptide 's

similarity to several human proteins [18]. However, an

antibody, found in both HIV positive and HIV negative

individuals, seems to have reactivity to this region of the

gp120 molecule.

 

 

A computer-assisted search of the Swiss-Prot database

reveals vasoactive intestinal peptide (VIP) as the best

match to NTM among currently analyzed human proteins [8,9].

The antibodies reacting to NTM may therefore be auto-

antibodies against VIP.

 

 

VIP is a small naturally occurring peptide, which plays

several important roles in the human body as a vasodilatator

(dilates blood vessels), neurotransmitter, and modulator of

the immune system.

 

 

VIP stimulates natural killer (NK) cells in the immune

system (among the first line of defence against infection)

and also the production of cytokine, a hormone that

influences the activity of other cells in the immune system.

VIP therefore has a very important role in modulating the

immune system.

 

 

The HIV protein gp120 is sufficiently similar to VIP to

serve as a molecular mimic and interfere with its function.

The main consequence of this mimicry is to undermine the NK

cells, making them dysfunctional, which is common in HIV-

infected subjects. As Peruzzi and co-workers demonstrated,

gp120 inhibits the ability of NK cells to kill infected

cells, and this inhibition affects also the production of

the pro-inflammatory cytokine IFN-gamma [19], which enlists

the help of other cells in the immune system to fight the

infection.

 

 

Thus, increase in circulating VIP can counteract the effects

of the HIV gp120, by overcoming the latter's inhibition of

NK cells, and by stimulating the production of VIP auto-

antibodies which can also bind gp120 and prevent it from

binding to NK cells.

 

 

Finally, both VIP and the peptide NTM has been previously

identified as possessing sequence characteristics

responsible for the interaction between HIV and the CD4

receptor [20], which represents the first step in process of

infection.

 

 

It has also been demonstrated that sera from HIV-negative

asthma patients contains high levels of natural anti-VIP

antibodies with peptide NTM reactivity. A recent study on

sera from 393 HIV- blood donors found that approximately 5%

(21/393) contain significant levels of the anti-VIP/NTM

antibodies, corresponding to two standard deviations above

average.

 

 

For HIV+ individuals, the amount of anti-VIP/NTM antibodies

available appears to strongly correlate with progression of

HIV disease, suggesting that the immune system is attempting

to overcome the infection. HIV patients in the first stage

of illness (characterized by CD4 lymphocytes count greater

than 500/ml), when the immune system is efficiently

controlling HIV, have very low levels of anti-VIP/NTM

reactive antibodies, similar to levels in normal HIV- people

[21].

 

 

The level of these antibodies significantly increases in

disease stages corresponding to CD4 values between 200 and

500/ml. Below that CD4 level (less than 200/ml), however,

the amount of anti-VIP/NTM antibody sharply decreases. In

the terminal stages of AIDS disease, NTM-reactive antibodies

in sera of HIV+ patients appear to be significantly

decreased.

 

 

Neurath and co-workers have also reported differences in the

spectrum of antibodies against HIV gp120 in two groups of

HIV-infected individuals, those who remained healthy for at

least 10 years, and those who developed AIDS within 5 years

of the onset of infection [6]. They found antibodies

recognizing the peptide 280-306 of HIV-1 gp 120 (overlapping

NTM) significantly more prevalent in asymptomatic carriers

than in AIDS patients. Thus, the absence or disappearance of

these antibodies may be a possible factor contributing to

the development of AIDS [6].

 

Exercise as a natural source of VIP/NTM reactive antibodies

 

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

 

A unique method to produce high titers of VIP/NTM reactive

antibodies may be available to both HIV- and HIV+

individuals. An article by Paul and Said in 1988 [10] showed

that auto-antibodies to VIP were present in plasma from

29.6% of healthy (HIV-) human subjects who habitually

performed aerobic muscular exercise, compared to 2.3% of

healthy subjects who did not. The exercise involves running,

cycling, swimming, aerobic dancing, and/or weight training,

three or more workouts per week for a year or more prior to

the study. The antigenic stimulus for the formation of these

auto-antibodies could not be identified from their data.

However, acute exercise has been shown to be associated with

a brisk increase in plasma levels of VIP [22,23]. It is

possible therefore that the antibodies may have been

produced in response to increased VIP levels during

exercise.

 

Effect of aerobic exercise training on HIV-positive

individuals

 

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

 

Several studies on aerobic exercise training in HIV-positive

individuals have demonstrated that it is safe, effective,

and has a number of beneficial outcomes [24-38]. The aerobic

exercise fitness improvements include a 10-25% improvement

in lactic acidosis threshold (a sign of fatigue) and 5-10%

increase in maximal oxygen uptake depending on the exercise

training intensity. In addition, despite concerns about the

stress of aerobic exercise on already damaged immune systems

(specifically, increases in infections, morbidity, or

mortality), there have been no documented adverse effects of

aerobic exercise training in HIV-positive patients at either

moderate or heavy exercise training levels [25]. The

available literature clearly supports the idea that aerobic

exercise is well tolerated by HIV-positive individuals.

 

 

With regards to immunologic improvement with aerobic

exercise training, CD4 counts or viral loads may or may not

improve during the exercise intervention in exercise (see

below), although skin test reactivity to Candida antigen has

been shown to improve with moderate exercise. The quality of

life outcomes, however, were found to have improved

significantly with aerobic exercise training relative to a

non-exercising control group.

 

 

There are indications that exercise can stabilize CD4 cell

count in HIV-infected individuals. Studies showed that

people with CD4 cells between 200 - 500 /ml seemed to

benefit the most from an exercise program. A pilot study

performed by Olson and co-workers found that the mean change

in CD4 percentage over the 24 months interval for weight

lifters was -3.1% compared with -5.9% for runners [26].

According to these researchers, among HIV infected patients

motivated to and capable of regular strenuous exercise,

weight training may offer a salutary benefit superior to

intense running. The same authors have also reported a case

of a long-term survivor (12 years HIV+) of a tri-athlete

with a rigorous daily exercise regimen demonstrating very

low viral burden as reflected in non-detectable HIV RNA

quantitative PCR and increase in CD4 during 6 years from 3

to 50 /ml (usual CD4 cell count is > 800 /ml) [27]. There

was a report that exercise facilitated a return of the CD4

cell count to more normal levels [28].

 

 

In a large study involving 415 individuals (156 HIV positive

and 259 HIV negative) Mustafa and co-workers demonstrated

that exercising 3 - 4 times/week had a more protective

effect than daily exercise [29]. Exercise in the HIV

positive group covered by this study showed an increase in

CD4 count during a year by a factor of 7%. It should be

noted that some authors have reported moderate training can

be sustained without any large change in CD4 cell count [30-

32].

 

Exercise for the masses

 

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

 

Aerobic exercise training has been shown to be a promising,

non-toxic, non-drug adjunct therapy to improve physical

fitness, increase quality of life, and potentially improve

the immune status (as indicated by reactivity to Candida

skin test) of HIV-positive individuals. If aerobic exercise

training can also be shown to increase the titer of anti-

VIP/NTM antibodies in normal individuals (potential to

decrease the risk of HIV transmission) and in HIV-positive

individuals (potential to slow disease progression), it

would strengthen its case to serve as a widely available and

affordable intervention that is non-toxic and free of drug

interactions. It would be applicable worldwide, in both

developed and developing countries.

 

 

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