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| | Interviews with Nutritional Experts: Antioxidant Nutrients and AIDS: Exploring the Possibilities | |
Interview with Dr. Luc Montagnier
as interviewed by Richard A. Passwater PhD
It doesn't seem like too many years ago that we learned of a dreadful
new and mysterious disease that threatened to wipe out mankind. Little was
known about this new disease, but it was rapidly spreading and some projected
that it would be killing us by the millions within a few years and bankrupting
our health care system along the way. Fortunately, this hasn't happened,
and a large part of the reason why it has not is that scientists led by
Dr. Luc Montagnier of the Pasteur Institute in Paris, determined the cause
of the disease we now call Acquired Immune Deficiency Syndrome (AIDS) and
how it's transmitted.
AIDS was formally recognized as a new disease in 1981. It is characterized
as the breakdown of the body's immune system due to selected cells in the
immune system being changed or their availability changed. These changes
result in defects in immune function which then allows "opportunistic"
infections that healthy people normally fight off to readily infect and
soon kill AIDS patients. During 1980, there were a few reports of certain
diseases such as rare cancers and serious infections that normally don't
kill healthy people leading to quick "wasting" of the patient
and rapid death. [1,2] The Centers for Disease Control established a task
force led by Dr. James Curran to look for other cases, present and past,
and to learn what they could about these alarming new reports. The earliest
confirmed case they could find at that time was in 1978. These increasing
reports were not recognized as a common disorder of the immune system until
1981. It was found that these patients had a depletion of certain white
blood cells called T4- lymphocytes, which are cells that play an critical
role in defending against invading organisms. Later investigation has identified
several other immune changes, but the depletion of CD4+ T-helper
lymphocytes has been related to AIDS ever since its first description.
Thanks to the research of Dr. Montagnier and his colleagues, the cause of
this mysterious disease which behaved differently from normal viral or bacterial
infections, was uncovered by 1983. [3] As a result, most of us don't have
to worry about this disease and we don't give much thought to Dr. Montagnier's
discovery. As an example, you can receive a blood transfusion today and
not have to worry about Human Immune Deficiency Virus (HIV), the AIDS virus,
being transmitted to you in the blood you receive. The fact that a test
had been developed to detect HIV in blood was a comforting thought to me
when I needed blood a few years ago. Even those who are at risk owe a huge
"thank you" to Dr. Montagnier because the discovery of both HIV-1
and HIV-2 strains of virus that is the cause of AIDS has led to preventive
measures that can protect those at high risk.
Dr. Montagnier's discovery goes beyond the development of measures to prevent
the transmission of AIDS; it provides a means to identify those who are
infected and allow treatment at an early stage, it also provides a means
to develop a protective vaccine and drugs to cure AIDS. Otherwise, we would
still be in the dark while AIDS would be mysteriously spreading throughout
the general population, not just the high-risk groups. The fact that AIDS
is being contained in developed countries by education and testing, while
it is pandemic in developing counties, is testament to the effect of Dr.
Montagnier's discovery.
AIDS is still a serious epidemic, but in the countries that take advantage
of the knowledge provided by Dr. Montagnier's discovery, AIDS is under considerable
control, rather than being pandemic as it is in other developing countries
without extensive public health measures. Poverty, lack of education and
exploitation of women can be considered risk factors for AIDS, and these
are common factors in many of the developing countries. However, AIDS itself
is only the tip of the iceberg of the HIV-infection. Although there was
an estimated 13 million HIV-positive people worldwide in 1993, about eight
million of those were in Sub-Saharan Africa. (In Africa, the transmission
route of AIDS is different and the presenting symptoms are different than
in the U. S. as will be discussed later.) The estimate for North America
was about one million, Western Europe about one-half million, Latin America
and the Caribbean was about one-and-a-half million, and South/Southeast
Asia about one-and-a-half million. Of those who have contracted HIV worldwide,
over two million had developed AIDS and died by mid-1993. Since the first
reported cases in the U. S. in 1981, over 402, 000 AIDS cases and more than
241,000 AIDS deaths had been reported through mid-1994
In November 1993, Drs. Linus Pauling and Raxit Jariwalla of the Linus Pauling
Institute of Science and Medicine, and I had the privilege of lecturing
to the Institute for Optimal Nutrition (ION) in London, along with several
European scientists. After the ION lectures, Dr. Jariwalla and I were invited
to speak at the Faculty of Medicine in Paris, standing on the same stones
in the floor of the Grand Amphitheater that Louis Pasteur had given his
lectures in the 1850s and 1860s as professor of chemistry and dean of the
school of science.. Dr. Jariwalla spoke on his research in slowing HIV replication
with vitamin C and I spoke on antioxidants in the prevention of cancer and
slowing the aging process. After the lectures, I visited the Pasteur Hospital
and the Pasteur Institute to survey their research on AIDS. I missed Dr.
Montagnier, who is the Head of the Department of AIDS and Retroviruses,
at that time, as he was out of the Country, but I was able to meet with
him on my next visit on May 3, 1995.
Dr. Montagnier was kind enough to bring me up to date on his continuing
research and particularly his research on the role of antioxidant nutrients
as a key part in slowing the progression of HIV infection to the AIDS stage.
You may also be interested in learning of the research into the possible
roles of antioxidant nutrients and plant extracts in slowing the progression
to AIDS. Dr. Montagnier has agreed to share part of our conversation with
you.
Passwater: Dr. Montagnier, your experience at the Pasteur Institute
was invaluable in leading you to isolate and identify the HIV virus. It
was only fitting that the virus be first identified here at the institute
that Louis Pasteur started over 100 years ago (1888) to treat rabies and
to further his research on "germs." Pasteur's discovery that many
diseases are caused by "germs" is a cornerstone of modern medicine
and became the foundation for the science of microbiology.
You headed the Viral Oncology department since 1972, the Virology Department
since 1982, and since about 1991, you have been Head of the Department of
AIDS and Retroviruses.
You have been Professor and Director of the Virology course at the Pasteur
Institute since 1980 and you are now the President of the World Foundation
for AIDS Research and Prevention. The Pasteur Institute has been a world
leader in virus research for decades, and has produced breakthroughs with
vaccines for malaria, diphtheria, and tuberculosis. Several new viruses
have been identified here and new cancer treatments have been developed
at this prestigious Institute. With this experience and background, what
made you suspect that AIDS resulted from a retrovirus infection, rather
than a virus related to hepatitis B, or Epstein-Barr, or cytomegalovirus
as others were suspecting? Was it the observed T-cell destruction leading
to immune depression?
Montagnier: There were some models, such as with the mouse leukemia
virus, suggesting that retroviruses of animals could induce immuno suppression.
We had the techniques from our cancer research before the AIDS problem came
along and we had the tools to detect retroviruses. It was not just my own
ideas, it was ideas from my colleagues, plus some ideas coming from the
U. S. as well.
Passwater: What led you to the isolation of what you first called
Lymphadenopathy Associated Virus (LAV), which after acceptance as the cause
of AIDS, had its name changed to HIV by the International Committee on Nomenclature
of Viruses. Was it because AIDS patients had enlarged lymph nodes?
Montagnier: Yes, at that time we knew that most AIDS patients started
with swollen lymph glands, and because many infectious agents are trapped
in the lymph glands, it was logical to look there. We wanted to look at
where the disease started so as to lessen our chances of following some
agent that entered the scene later as an opportunistic invader. Opportunistic
agents are normally found in the environment and they are harmful only to
those having weakened immune systems. We had to find the causative agent,
not an opportunistic agent.
Passwater: Was HIV easy to identify?
Montagnier: The first HIV (LAV at the time, now called HIV-1) was
very difficult to grow in vitro (in laboratory glassware). Most viruses
are far easier to grow in vitro than HIV is. This HIV was non-cytopathic
and could have been overlooked. In many patients there are some changes
in the virus with time, and the viruses isolated at the next stage of infection
are more virulent and more cytopathic. Taking blood samples rather than
lymph samples would not have isolated the original virus. The mutated viruses
can be propagated in some cell lines, but the early form of the virus is
not. Thus, we had a difficult time, at first, convincing others that the
virus we isolated and identified was the causative agent for the infection
that progresses to AIDS.
Passwater: How long has the HIV virus been around?
Montagnier: In my opinion, a very long time before the AIDS epidemic.
HIV may have been in Africa for centuries.
Passwater: Why did HIV infection and AIDS suddenly become epidemic
about 1980?
Montagnier: HIV has been around for awhile -- it is only our behavioral
changes that have caused the pandemic. AIDS is a complex disease. There
are four factors that have come together to account for the sudden epidemic;
HIV presence, immune hyper-activation, increased sexually transmitted disease
incidence, sexual behavioral changes and other behavioral changes. All of
these factors had to occur essentially simultaneously for HIV transmission.
The first factor is the HIV virus, which is the causative factor without
which there would be no AIDS. However, the other three factors are secondary
factors or co-factors that make the HIV virus more easily transmitted from
one person to another, and thus make the infection epidemic.
The second factor that is involved is that there must be hyper-activation
of the immune system. What is striking in HIV infection is that abnormal
activation (T cell receptor stimulation) of infected cells is continuous
and lasts throughout the entire course of the disease, including pre-clinical
and clinical stages. Apoptosis (programmed cell death) occurs rapidly after
lymphocyte cell activation. The continuous CD4 cell depletion is the result
of multiple mechanisms and the impairment of T4- cell renewal may contribute
to CD4 cell depletion.
The HIV was already in Africa and Africans often have hyper-activated immune
stimulation because in the tropics there are many infections caused by microbial
parasites, fungi, viruses, etc., that stimulate the immune system. The stimulated
immune system provides more targets for the HIV virus to invade. The CD4
differentiation antigen of the T- lymphocyte is the major cell surface receptor
for HIV, thus the more CD4 activated T- lymphocytes, the more targets for
HIV to infect.
The third factor involves changes in sexual behavior that resulted in more
Sexually Transmitted Disease (STD) activity. The presence of conventional
STD such as syphilis or chancroid increases the risk of HIV transmission
by ten-to-a-hundred times. The birth control pill -- introduced about 1960
-- has led to more "sexual freedom" and with this new freedom
has come change.
The fourth factor involved other behavioral factors. Behavioral factors
include drug use, poor nutrition, stress, wider travel and migration, social
changes, and the like.
Passwater: Thanks to your research and others, we have learned much
about the transmission of HIV and how to prevent it. We know that HIV is
transmitted mostly through blood and semen, but HIV is also present in --
although difficult to transmit via -- saliva, urine, tears, breast milk,
vaginal and cervical secretions. Your research has led to the recognition
of the three primary routes of transmission -- sexual intercourse (vaginal
or anal) with an HIV-infected person, contact with HIV-infected blood or
blood-products, and by infection passed from mother to child during pregnancy
or birth. U. S. statistics for the late 1980s indicated that the high risk
groups were homosexual and bisexual men (73 percent of cases) and intravenous
drug-abusers (17 percent of cases). The public has been educated about the
dangers of unprotected sex and dirty needles and these risks have been reduced.
However, are there other factors that might further help prevent the transmission
of HIV even in the educated, developed countries?
Montagnier: Well, two other cofactors for infection that come right
to mind are poor nutrition and stress. Studies show that nutrition is a
factor in immune system function. Likewise, psychological stress activates
T- cell growth factors which could hyper-activate the immune system.
Passwater: Let's turn from HIV transmission to HIV progression
to the AIDS stage. Some people develop AIDS more quickly than others after
HIV infection. HIV appears to "lie dormant" for several months
for a few people, while in most may not develop immune problems for several
years, and in rare cases, some may go as long as ten years before detectable
immune dysfunction. (Although the infection appears to be dormant, the virus
is replicating actively in lymph nodes and lymphatic tissue and apoptosis
is occurring.) Let me draw a graph to represent this progression through
two major stages. Let point "A" represent the time that a person
becomes infected with the HIV virus and is called "HIV-positive."
Up until now, we have been discussing those factors that either facilitate
or protect against "A." Now let point "B" represent
the time that progressive T- and B-cell dysfunction begins. (T- and B- cells
are immune system components and their decline in function reduces the body's
resistance to disease and infection.)
0 HIV-infection (point A) progresses through several stages. This is illustrated
here by point A, the time of HIV-infection, by point B, the final HIV-infection
stage called AIDS which is the time of noticeable progressive T- and B-cell
dysfunction, that leads to death (point C). The time scale has no dimensions
due to the fact that this period varies from individual to individual.
What can be done to extend the time between HIV infection (point A) and
the beginning of serious immune problems (point B)?
Montagnier: Our goal in following those people who are HIV-positive,
but asymptomatic is to learn how to delay this progression or to completely
halt it. I think that this is possible. There are examples in animals where
they are infected with Simian Immune deficiency Virus (SIV, a monkey retrovirus
similar to HIV) and yet they are not sick. So we have to understand the
complex action between the virus and the immune system. We have to try to
make the immune system take over the virus, and not the other way around.
The complex pathophysiological basis of the profound and seemingly irreversible
immune depression that follows this retroviral infection is still obscure.
At present our best hope is to prevent further immune depression. Based
on animal studies, the indicator as to how fast the immune system fails
is in the lymph nodes. We have shown that when there is rapid HIV replication
in the lymph nodes at an early time, then there is rapid acceleration towards
AIDS. The rate of virus replication in the first few weeks after HIV exposure
is directly related to the progression. If the replication is high in the
first few weeks, then the progression is more rapid.
Oxidative stress is a key factor. There is a higher free radical production
in stage II of HIV infection that could be caused by several factors including
the overproduction of oxygen radicals by polymorphonuclears. The key may
be to reduce oxidative stress at the earliest stage of HIV infection. Antioxidants
and AZT or other drugs could be used at this stage to prevent progression
to AIDS. If the oxidative damage is slowed, then the progression may be
slowed or halted.
I strongly believe that one important factor is the activation of the T-helper
cells. Consecutive T-cell receptor stimulation induces T-cell deletion by
apoptosis. [4] Recognizing the importance of apoptosis in AIDS progression
may have dramatic implications for developing new treatments for AIDS. Apoptosis
may induce oxidative stress. We know also that oxidative stress can mediate
apoptosis. This is a circular cascade.
Being able to reduce apoptosis to a normal rate in lymphocytes of HIV-infected
individuals would put HIV infection in a class with mononucleosis and other
chronic infections where cell death does occur, but the immune system goes
back to normal after a period of time. In the middle and later stages of
HIV infection, apoptosis is a chronic and permanent problem. Antioxidants
including NAC might slow the rate of apoptosis. Apoptosis is not limited
to HIV infection, but proceeds at a higher rate in HIV-infected cells.
Other cofactors may be some ordinary proteins or some external factors which
are present before infection or even carried along with the HIV, and oxidative
stress. If we act on the causative agents that lead to increased apoptosis
-- free radicals, microbial factors, viruses -- or interact with the many
steps of the apoptosis process, we can reduce cell death to a normal rate.
We should treat oxidative stress at the earliest possibility. This requires
measuring the oxidative stress markers in the blood and tailoring the treatment
to the individual based on the results of these tests.
Passwater: What might be done to "flatten" or extend the
time between point "B," the beginning of progressive T- and B-cell
dysfunction and point "C," death?
Montagnier: That's more difficult than treating it earlier. I won't
say it is impossible, perhaps gene therapy might be useful. Still antioxidants
and drugs might delay the more rapid decline.
Passwater: Have you investigated N-acetyl cysteine or other antioxidants
as possible mediators of the progression to AIDS?
Montagnier: Yes. We have started some open trials with NAC following
the work of the Herzenbergs at Stanford and that of Droge in Germany. In
HIV infected patients, the glutathione system is depressed even at early
stages. The rationale is to restore the oxidative protection system back
to normal. When we treat patients for less than six months with NAC, we
don't see much change. However, when the NAC treatment is longer than six
months, NAC will restore apoptosis back to normal levels. This is a preliminary
result and we will repeat the study in our new applied research laboratory..
We plan to open a new research center at the end of this year for HIV asymptomatic
patients, in which we will follow a battery of laboratory markers and treat
patients accordingly.
I am convinced that oxidative stress is indeed involved in the progression
of going from HIV infection to the AIDS stage. I believe, therefore, that
antioxidants are necessary in the treatment , but antioxidants are not sufficient
by themselves.
I advocate adapting the treatment to the patient. Antioxidants are important,
but in order to be effective, they must be rationally used. We must take
into account the parameters of each individual. Some may lack selenium,
or zinc, or vitamin E, or other nutrients, or any combination. So our treatment
must be planned according to these parameters, and thus, our treatment may
change from one individual to another. The treatment must be adapted to
the individual to restore these parameters that we are measuring back to
normal.
We should monitor the markers of oxidative stress such as lipid peroxides
which increase when opportunistic infection occurs, as well as the carbonyl
content of lymphocyte proteins, cytokines and Tumor Necrosis Factor (TNF).
We have laboratory studies showing that the proteins of lymphocytes are
very rapidly degraded due to oxidative stress.
These parameters will be evaluated and then patient treatment may include
several antioxidants such as NAC, beta carotene, vitamins A, C and E, the
enzymes superoxide dismutase (SOD) and catalase, proteins such as metallothionine,
plant extracts and other nutrients as indicated.
Passwater: Will you give the SOD orally or by injection?
Montagnier: Both.
Passwater: I am pleased that you are using oral SOD, because so many
researchers have been dissuaded from using it because of a very questionable
report incorrectly claiming that SOD can't be absorbed orally due to its
molecular size.
Montagnier: There are ways to make SOD assimilable orally. Some preliminary
data support that oral SOD is sufficiently absorbed.
Passwater: Could you comment more on the use of plant extracts?
Montagnier: Plants have invented many more compounds than we have
and before we will. Plants are much richer sources of antioxidants and other
useful nutrients or pharmacologically-active compounds than man. Let nature
help us. They give us a wide spectrum of compounds to work with.
We should not try to purify plant extracts too much. They might contain
several compounds that are effective only when in combination with each
other.
Passwater: You have suggested that mycoplasmas could increase oxidative
stress and thus be a co-factor in how quickly HIV infection progresses to
AIDS.
Montagnier: In 1989 and 1990, I suggested that mycoplasmas may be
cofactors in some individuals. We are still investigating the role of mycoplasmas
trying to verify this hypothesis. We have several types of evidence. One
is the fact that from 20 percent of individuals to almost 40 percent at
the AIDS stage of HIV infection, have antibodies against mycoplasmas such
as Mycoplasma fermentans, Mycoplasma penetrans or Mycoplasma pirum.
Mycoplasma may play a role in signaling lymph nodes to start the integration
of HIV into cells where they can replicate. There is some evidence that
HIV replication does not take place in non-activated cells. The _____ mycoplasmas
is a silent infection, but they may influence HIV pathogenesis by contributing
to oxidative stress, or activating the immune system or producing superantigen.
Mycoplasmas could induce inflammatory cytokines and TNF. They could be sexually
transmitted along with HIV. [5]
Passwater: Is there a switch from "T-helper 1" response
to "T-helper-2" response which seems to promote the progression
to AIDS, and if so, is this "switch" affected by antioxidants?
Montagnier: This concept was put forth by Gene Shearer and Mago Clerici
at NIH. There is still some debate about it. It seems that it is not a clear
cut switch, but that there are some changes. What is observed in patients
progressing to AIDS, is an increase of cytokines which are involved in T-helper
2 immunity which promotes B-lymphocytes, but inhibit the cellular immunity
important in controlling HIV infection.
Passwater: Is the decline of T-cell proliferation and Interleukin-2
production decline, and the increase of interleukins -4, -5, -6 and -10,
plus immunoglobulin production affected by antioxidants or other nutrients?
Montagnier: I haven't seen evidence of this, but it is possible.
You have to tell me if you know. .
Passwater: Yes, I have seen some very preliminary results by Dr.
Ron Watson of the University of Arizona where the antioxidant Pycnogenol(R)
restored these immune components towards normal levels in a Murine AIDS
model in the mouse.
Does research at the Pasteur Institute suggest that there may be a second
HIV receptor, a co-receptor, which is a cell surface protein called CD26,
in addition to CD4?
Montagnier: I personally am not working on that, but some of my colleagues
are. This question is more complex that what it first appeared. The evidence
may not be convincing at this stage, but the research is not at a dead end,
however. CD26 may be involved in the induction of apoptosis along with the
CD4 receptor when the virus envelope glycoprotein gp120 binds to the cell.
Passwater: What can we do for the people of Africa where the AIDS
epidemic is now exploding?
Montagnier: We have seen that international campaigns to educate
the public about AIDS has almost brought AIDS under control in some developed
countries. However, this education is not efficient in some populations
with high drug use. Our educational efforts have almost completely failed
in areas where cultural and epidemic factors collide. Poverty is at the
root of many of Africa's problem, as are cultural factors. There is poor
hygiene where there is poverty. Where, in addition, there are poor conditions
for women then there is an AIDS pandemic. In Africa, AIDS is transmitted
mostly heterosexually,.and both sexes are nearly equally infected with HIV.
Most African males that are HIV-positive are promiscuous heterosexuals,
and many of the females with HIV infection are prostitutes. There are areas
where the culture dictates that women cannot resist sexual contact with
men. In some areas, single men are sent to work and they are supplied with
prostitutes, who are often HIV-infected. In these areas STD are high. HIV
is the virus that causes AIDS, but as we discussed earlier, cofactors such
as STD and parasite infection increase the efficiency of spreading the infection.
Poor nutrition resulting from the poverty handicaps the immune system. The
lack of availability of medical treatment allows these cofactors to be rampant.
This is why studying the cofactors is so important in these countries.
We can reduce the pandemic even without a vaccine. If we can improve hygiene,
or provide chlorine bleach to disinfect, or even electricity, we can reduce
the spread of AIDS in Africa. If we could improve the economic conditions
and educate the population, we could do much more.
Even though AIDS is not spreading out of control in our countries, we must
be vigilant and try to do something for the rest of the world. It is the
humane thing to do, and otherwise we can't eradicate AIDS in developed countries.
There will still be a danger as long as HIV infection is epidemic anywhere
on Earth.
This is why I created, along with Federica Magor, the World Foundation for
AIDS Research and Prevention. Our immediate goal is to launch three or four
centers in sites where HIV infection is high.
Passwater: Well, you have accomplished so much. I know your empathy
for the people, but only political solutions may help there. Let's look
ahead. What's next in your research.
Montagnier: There are many pressing problems. Before working on AIDS,
I was doing cancer research. I want to get back to that, and to also study
Alzheimer's disease, heart disease and arthritis. There is so much to do.
Passwater: Yes, there is. Even though you have done so much already.
Thanks for taking the time to bring us up to date. Who knows, maybe one
of our scientific readers will get an idea from your discussion and help
solve some of these problems.
REFERENCES
1. M. S. Gottlieb and I. Pozalski, Morb. Mortal. Wk. Rept. CDC, 30:250-2
(June 5, 1981)
2. A. Friedman, Morb. Mortal. Wk. Rept., CDC, 30:305-8 (July 3, 1981)
3. F. Barre-Sinoussi et al., Isolation of a T-lymphotropic retrovirus from
a patient at risk foracquired immune deficiency syndrome (AIDS), Science
220:868 (May 20, 1983)
4. M-L. Gougeon and L. Montagnier, Apoptosis in AIDS, Science 260:1269-70(May
28, 1993)
5. A. Blanchard and L. Montagnier, AIDS-associated mycoplasmas, Ann. Rev.
Microbiol.48:687-712 (1994)
All rights, including electronic and print media, to this article are copyrighted
by © Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.)
| Richard A. Passwater, Ph.D. has been a research biochemist since 1959. His first areas of research was in the development of pharmaceuticals and analytical chemistry. His laboratory research led to his discovery of......more |  |
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