Antioxidant Nutrients are Important in Slowing the Progression to AIDS from HIV Infection: An Interview with Dr. Luc Montagnier, the Discoverer of HIV
by Richard A. Passwater, Ph.D.
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, except that it was rapidly spreading. 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 due to Dr. Luc Montagnier of the Pasteur Institute in Paris. He and his colleagues discovered the cause of the disease we now call Acquired Immune Deficiency Syndrome (AIDS) and determined how it's transmitted.
AIDS was formally recognized as a new disease on June 5, 1981 when the Centers for Disease Control (CDC) reported that five Los Angeles men had developed an unexplained immune deficiency. It is characterized as the breakdown of the body's immune system due to the decrease of selected cells in the immune system. This decrease results in defects in immune function which then allows "opportunistic" infections that cannot infect people with healthy immune systems to readily infect and soon kill AIDS patients. During 1980, there were a few reports of certain diseases such as rare cancers and infections leading to quick "wasting" of the patient and rapid death. [1,2] There particularly was an increase in cases of Pneumocystis carinii pneumonia and herpes simplex. This was followed by an increase in the incidence of Kaposi's sarcoma.
The CDC 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. AT that time, the earliest confirmed case they could find occurred in 1978. As the number of similar reports increased, they were recognized as a common disorder of the immune system in 1981. It was found that these patients had a depletion of certain white blood cells that play a critical role in defending the body against invading organisms. These cells were formerly called T4- helper lymphocytes, but now by international convention are called CD4 lymphocytes. (CD stands for cluster of differentiation markers.) Because immunology knowledge is rapidly expanding and terminology is perplexing and changing, a glossary for the relevant terms used in this discussion is provided in table 1.
Later investigation has identified several other immune changes, but the depletion of CD4 lymphocytes has been related to AIDS ever since its first description. With the dramatic reduction in number of CD4 lymphocytes, the ratio of CD4 to CD8 cells changes, which is often used as a marker of the disease progress.
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 relatively quickly in 1983.  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) which is the virus that causes AIDS, 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 high risk owe a huge "thank you" to Dr. Montagnier because his discovery of both HIV-1 and HIV-2 strains of the virus has led to protective preventive measures.
HIV is an unusual virus. It is a retrovirus which means that it reverses the normal pattern of replication. Its genetic material contains only RNA instead of DNA. Retroviruses depend on an enzyme called reverse transcriptase to use the genetic material in the white blood cells that they infect to make the proteins needed for the virus to survive. In essence, the HIV turns the white blood cell into a factory to churn out more HIV. HIV is also a lentivirus which means it produces a disease that is slow to develop. The structure of HIV is discussed in more detail in the November 1994 interview with Dr. Will Taylor. In essence, HIV is a spherical virus with several protein coats. The proteins (antigens) on the outside envelope allow HIV to attach to CD4 antigens and infect the T lymphocyte. (The CD4 glycoprotein becomes a receptor for HIV in certain differentiated T lymphocytes. See glossary for more details.)
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 entire 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 a testament to the effect of Dr. Montagnier's discovery. By comparing earlier rates (e. g. 1988) of AIDS propagation to the actual recent rate, I estimate that Dr. Montagnier's discovery has saved more than two million lives worldwide and about 400,000 American lives already (see figure 1).
In the countries that have taken advantage of the knowledge provided by Dr. Montagnier's discovery, AIDS is under considerable control. In countries that have not implemented extensive public health measures based on Dr. Montagnier's discovery, AIDS is still a staggering pandemic. 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. Perhaps you have seen the public service announcement on TV that jolts you with the fact that one in 250 Americans is HIV-positive! Estimates for future AIDS cases vary. In 1994, an expert panel predicted that there will be 30-to-40-million persons worldwide infected with HIV by the year 2000. Currently, there is wide agreement on an estimate that there were 13 million HIV-positive people worldwide in 1993, with about eight million of those being in Sub-Saharan Africa. In central Africa, 70-80 percent of hospital beds are occupied by AIDS patients. (In Africa, the transmission route of AIDS is different and the presenting symptoms are different from those in the U. S. This 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. The economic toll is also a factor with direct costs of AIDS estimated to be about $350 billion, and the indirect costs much higher.
Of those who have contracted HIV worldwide, more than two million had developed AIDS and died by mid-1993. Since the first reported cases in the U. S. in 1981, more than 402, 000 AIDS cases and more than 241,000 AIDS deaths had been reported through mid-1994. In comparison, in its worse year, 1952, the number of U. S. paralytic polio cases was about 21,000.
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 clinical 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 was first identified here at the institute that Louis Pasteur started more than 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 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 immunosuppression. 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, and some ideas coming from the U. S. as well.
Passwater: Fortunately, the AIDS epidemic did not occur before we understood as much as we did about the immune system and retroviruses. 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 clinical 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 a while -- only our behavioral changes 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. (An activated lymphocyte is any lymphocyte in an active state of proliferation or differentiation.) The continuous CD4+ T lymphocyte cell depletion is the result of multiple mechanisms and the impairment of this cell's renewal may contribute to its 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 -- breast milk, vaginal and cervical secretions (HIV antigens are also present in saliva, urine and tears, but as the TV public health message says, "you don't get AIDS by kissing."). Your research has led to the recognition of the three primary routes of transmission -- "unprotected" sexual intercourse (vaginal or anal) with a HIV-infected person, contact with HIV-infected blood or blood-products, and by infection passed from mother to child during pregnancy or birth, and even via breast-feeding. 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). (Intravenous drug users spread HIV primarily via sharing blood-contaminated needles.) 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: You have stressed that hyper-activation is a key in HIV infection and transmission. For the benefit of our readers who are not immunologists, T cells are at rest until "activated." Activation leads to RNA and protein synthesis. The glossary explains more about this process.
Let's turn from HIV transmission to HIV progression to clinical AIDS. Some people develop clinical AIDS more quickly than others after HIV infection. Currently, most HIV infected persons will die within eight-to-ten years of infection. The period of time varies, however, and HIV does not produce symptoms for several years in most people. In approximately five percent of HIV-infected persons, this period may exceed ten years before detectable immune dysfunction is observed. Although the HIV infection is not producing symptoms, it is not dormant, the virus is replicating actively in lymph nodes and lymphatic tissue and apoptosis is occurring. HIV causes T cells to produce more virus particles before these infected T cells die. When infected cells are "activated," viral expression can be increased by 50-fold. The new generation of infected T cells in turn produce more virus particles and then this generation of T cells dies. At first, the body is able to keep pace with T cell death by replacing them with new T cells, however, as the number of infected T cells grows astronomically, the body can't keep pace, thus T cell population swiftly declines and symptoms are observed.
Let me draw a graph to represent this progression through two major stages (figure 4). Let the 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.
What can be done to lengthen the course from HIV infection (point A) and the beginning of serious immune problems (point B) and clinical AIDS?
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 toward 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.  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 the 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 such as lipoic acid and curcumin 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, interleukins (chemical intercellular messengers that regulate cell functions) and Tumor Necrosis Factors (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?
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: When you mention plant extracts, ginkgo biloba, turmeric and Pycnogenol(R) come to mind. 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 cofactor 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 to almost 40 percent of individuals 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 produce 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 interleukins and TNF. They could be sexually transmitted along with HIV. 
Passwater: There seems to be some evidence from laboratory animals that there are subsets of T-helper cells called "T-helper-1" and "T-helper-2," and that these subsets have slightly differing functions with T-helper-1 cells leading to their continued proliferation, while T-helper-2 cells promote an increase in B cells. They are conjectured to be "cross-regulated" interferon-gamma and interleukins -4 and -10. I realize that there is no broad consensus that these subsets exist in man. Could you speculate on whether or not a switch from "T-helper 1" response to "T-helper-2" responses could promote the progression to AIDS, and if so, would this "switch" be affected by antioxidants?
Montagnier: This concept was put forth by Gene Shearer and Mario Clerici at NCI. 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 interleukins 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 and interleukin-2 production, and the increase of the 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 toward 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 than 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: The AIDS pandemic in Africa is frightening. There are countries where poverty, culture, politics and the suppression of women are combining to fuel the AIDS pandemic. These conditions increase the efficiency of HIV transmission as you mentioned earlier. In Uganda and Tanzania, HIV-infection rates are higher in women than in men. In addition, females are infected at earlier ages than males. According to the World Health Organization, in some urban centers in east and central Africa, between one-quarter and one-third of all women and men between the ages of 15 and 49 years are HIV-positive. Uganda is a big concern. The life expectancy there is approximately an average of 40 years. There is hunger, poverty, diarrhea, malaria, plague, cholera, yellow fever, meningitis, AIDS and even the ebola virus which was identified in 1976. There are few older adults. Mostly you see younger children with one parent.
There is not much spent on health education or health care in many African countries. According to the World Bank, the yearly per capita health care spending in Tanzania and Ethiopia is about $4, Uganda $6, Zaire $8, Nigeria $9, Sub-Saharan Africa $24, Zimbabwe $42, and South Africa $ 158. In government hospitals in Kenya, it is common to see two or three patients in a bed, with no basic supplies or medicines, and certainly with poor hygienic conditions.
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 provide education about HIV transmission, 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. Not only in third world countries, but everywhere! As long as HIV-positive persons are discriminated against, those who should volunteer to be tested for HIV will not come forward for fear of losing their jobs and/or insurance. Many years ago when it was mandatory to for hospital patients to be tested for syphilis, there was no civil rights issue because people did not lose their jobs or insurance if they were syphilis carriers.
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.
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 for acquired immune deficiency syndrome (AIDS), Science 220:868 (May 20, 1983)
4. M-L. Gougeon and L. Montagnier, Apoptosis in AIDS, Science 260:1269-7 (May 28, 1993)
5. A. Blanchard and L. Montagnier, AIDS-associated mycoplasmas, Ann. Rev. Microbiol. 48:687-712 (1994)
Acquired immunity - Immune resistance that develops following initial exposure to an antigen (a)
Activation of T cells - T cells are normally at rest. The "activation" of T cells leads to RNA and protein synthesis. Activated T cells secrete IL-2. Two signals are required to activate resting T cells. One signal through CD3 and the other through IL-1 from antigen-presenting cells. (b)
AIDS - Acquired Immune Deficiency Syndrome (or also Acquired immunodeficiency syndrome).
Antigen - A substance, usually a protein, that causes the formation of an antibody and reacts specifically with that antibody. (d)
Apoptosis - Developmental or "programmed cell death characterized by membrane blebs, extensive chromatin condensation, and DNA fragmentation. Plays a role in negative selection of developing T cells and the killing of targets by cytotoxic T lymphocytes. (a)
B cells - B lymphocytes. These cells originate and mature (differentiate) in the bone marrow and live for a few days. They are responsible for the branch of the immune response called "humoral immunity." B cells are cells that rearrange and express immunoglobulin genes, i.e., produce antibodies.
CD markers - Cluster of differentiation markers. Cell-surface molecules designated by international convention. (a) The CD markers on the lymphocyte surface are defined by a cluster of monoclonal antibodies all reacting with the same molecule. (b)
CD4 - Formerly called T4, is a marker of T-helper cells. Human CD4 is the receptor that serves as a docking site for HIV virus on T-helper lymphocytes. Binding of the viral glycoprotein gp120 to CD4 is the first step in viral entry, leading to fusion of viral and cell membranes. CD4 is often, but not always associated with T-helper function. CD4 is a glycoprotein present on the surface of a population of T cells that recognize antigenic peptides presented by class II MHC molecules. (a, d)
CD8 - Formerly called T8. Often, but not always, associated with cytotoxic effector function (suppression). A molecule present on the surface of a population of T cells that recognize antigenic peptides presented by class I MHC molecules. (a) Also called cytotoxic T cells. (d)
Cytokines - This term has generally been replaced by the term "interleukins" when discussing lymphocytes. Otherwise, this term refers to growth and differentiation factors not produced by lymphocytes.
Cytotoxic - Having the property of killing cells. (a)
HIV - Human immune deficiency virus (also human immunodeficiency virus). The virus that infects T cells and leads to AIDS. HIV is a type D retrovirus that belongs to the lentivirus sub-family. (c)
Interleukines - A group of growth and differentiation factors with immunological and other functions. (a)
IL-2 - Promotes growth of T cells, NK-cell activation, B-cell growth and differentiation. (a) Has the ability to initiate the proliferation of activated T cells. (d)
IL-4 - Promotes resting T-cell and activated B cell growth
IL-6 - Supports growth of T cells; B-cell differentiation.
IL-8 - T cell chemotaxis at high doses. (a)
K cell - Killer cell. A lymphoid cell (non-T, non-B) that bears Fc receptors allowing it to bind and kill antibody coated targets. (a)
Killer T cell - Cytotoxic T cell. (a)
Lymphocyte - A small white cell with little cytoplasm. T and B lymphocytes are responsible for all specific recognition of antigens. (b)
MHC - Major histocompatibility complex. A complex of highly polymorphic genes that encode the cell-surface molecules responsible for rapid graft rejection and needed for antigen presentation to T cells. (a)
MHC, class I - Major histocompatibility molecule which presents peptide antigen fragments to
CD8+ T cells. Expressed on nearly all cells and thus provides "self-identity."
MHC, class II -Major histocompatibility molecule expressed on antigen-presenting cells. These molecules present peptide antigen fragments to CD4+ T cells. (a)
Mycoplasma - A genus of ultramicroscopic organisms lacking rigid cell walls and considered to be the smallest free-living organisms. (d)
NF-kappa-B - Nuclear factor-kappa-B is a member of a novel family of transcription factors sharing a common motif for DNA binding and dimerization.
NK cell - Natural killer cell. A large, granular lymphocyte lacking immunoglobulin or T cell receptors that has the ability to recognize and destroy some types of tumor cells. (a)
Null cells - Lymphocytes lacking T or B markers. (a)
Retrovirus - Retroviruses proliferate by a process that is the reverse of normal viruses. Retroviruses contain a single positive-stranded RNA with the virus's genetic information and an enzyme called "reverse transcriptase" in their core. Reverse transcriptase enables the virus to convert viral RNA into DNA. This reverses the normal process of transcription where DNA is converted into RNA. (c)
T cells - T cells are lymphocytes that are produced in the bone marrow and mature in the thymus. T cells are responsible for mediating the second branch of the immune system called "cellular immune response." T cells can live for months to years. This lymphocyte population is defined by the presence of a rearranged T-cell receptor.
T-helper cell - Functional class of T cells that induces effector cell function by releasing growth and differentiation factors upon induction. T-helper cells are usually CD4+ and restricted to class II MHC. (a, b)
TNF - Tumor necrosis factor. Biologically active factors produced by macrophages and some T cells.
T-suppressor cell - Suppresses B cell activity. (CD8)