AIDS research - causes of AIDS - AIDS treatment video - retroviruses - protease inhibitors - cure? Antiretroviral therapy for HIV

AIDS research / video - causes of AIDS - AIDS treatment - retroviruses - protease inhibitors - cure? Antiretroviral therapy HIV

Note: This chapter of the Truth about AIDS by Dr Patrick Dixon is the original text as published by Kingsway in 1994 updated 2002 and may be reproduced with acknowledgment. Search this book.

Symptoms of HIV and AIDS - worried about yourself or someone you love?

Dr Patrick Dixon explains about HIV symptoms: what happens when someone is infected with HIV. Early symptoms of AIDS. Risks of transmission? Why some people get infected with HIV and not others. Dr Dixon is a physician and founder of the international AIDS agency ACET, with prevention and care programmes in many of the poorest nations. He is also Chairman of Global Change Ltd - future trends.
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Latest AIDS statistics, AIDS information - Africa AIDS Crisis - History of AIDS - AIDS epidemic, India, Asia, Eastern Europe, Central Europe, Russia, America, China

All viruses are dead. There is nothing alive in a virus at all. A virus is no more living than a computer game you can buy in the High Street. Bacteria are different: bacteria breathe oxygen or carbon dioxide, need warmth to grow, and they grow larger and divide into two. In fact bacteria behave like cells in your own body.

Some bacteria make poisons such as the tetanus toxin which causes rapid death. Others live quite happily on every corner of your body. An example is in your gut where bacteria help you to digest food. If you take antibiotics, some of these bacteria die and the result can be diarrhoea. So while some bacteria keep us healthy, others bring disease because of the poisons they make when growing.

You can see bacteria under the microscope. I have taken a swab from a man or woman's genitalia and touched a microscope slide with it. You can see the red gonorrhoea bacteria easily and make an instant diagnosis. In most cases a single large dose of penicillin will kill the bacteria. Penicillin works by weakening the cell wall that holds the little organism together. The bacteria swell, burst, and die. A swab containing syphilis organisms is even more interesting: these creatures swim like little eels, thrashing about on the wet glass slide. Instant diagnosis. Immediate high dose penicillin. Immediate cure in most cases.

But AIDS is caused by a virus (HIV). Thousands of bacteria can fit inside a cell in your body, but virus particles are so minute that hundreds of thousands of them could fit inside a single bacterium. They are totally invisible under a normal light microscope. Viruses cannot grow and cannot divide. They don't breathe, don't need food, don't live, and never die. All our technology has failed to produce a single non-toxic drug that attacks and destroys a virus efficiently.

The only real weapons we have against viruses are natural ones: antibodies which can also destroy bacteria. These are Y-shaped. The mouth of the antibody is shaped exactly to fit over part of a germ. Thousands of them lock onto a germ so that the tails bristle like a hedgehog. Sometimes that is enough to burst bacteria or to stop viruses from being able to touch a cell. Special white cells in the body stick on to these bristles and eat up the germ. These white cells are those that you find in pus, cleaning up an infected wound. The trouble with antibodies is that the body takes three days to produce the right antibody for the right virus. During this critical three-day period, the body is totally unprotected. Yet only an hour or two after viruses enter the bloodstream they have completely disappeared. You can hunt through the entire body cell by cell, with the best electron-firing microscope, and find nothing.

Why? Because every virus particle has disintegrated. Each one has burst like a soap bubble when it touches the ground.

The virus bag has disintegrated and vanished. What about the contents? They too have disappeared without trace, but the cell they touched has received the kiss of death.

A virus is a bag containing a short piece of coiled-up `string'. The string is formed entirely of four different chemicals arranged in an order. When stretched out, it reads like a language:

This language is what we call a genetic code. It is the language used by the nucleus (brain) of every cell in your body. A cell of your body under the microscope looks a little like an egg. It has a central round core called a nucleus and a more transparent-looking outer area. The nucleus is black and is packed full of your chromosomes. You have forty-six chromosomes which determined everything from the moment you were conceived, including the length of your arms, whether you have black or brown hair, whether you will be bald by the time you are thirty, your height, gender, basic build, the shape of your nose. Everything.

Each of these chromosomes is tightly coiled up like a spring. If we stretched out the message and then typed out the sequence, and put all the messages from all the chromosomes in one cell in your body into a book, that book would be the size of Encyclopaedia Britannica.

These instructions program not only your outside appearance, but also every type of cell in your body. Have you ever thought how a skin cell learned it was a skin cell and not a nail- or hair-producing cell? How does a cell know it should produce bone and not hormones? If I cut my hand, how does a skin cell know to divide and go on dividing until the gap is covered and then stop? The answer lies in that vast book of instructions. The amazing thing is that every cell nucleus in your body carries a carbon copy of your entire genetic code.

We have already succeeded in altering the genetic code of a bacterium so it contains a small piece of code taken from a human being. This piece of code tells the bacterium not to produce poison but to produce human insulin---previously diabetics were dependent on insulin obtained by crushing the pancreas of a pig or cow. This new strain of bacteria grows and divides for ever, with each new organism containing a perfect set of instructions for making human insulin.

In 2002 over 500,000 genetically-mutated animals were born in UK laboratories, each unlike any animal ever seen before. Human genes have been added to pigs to make them grow faster. The `superbreed' is blind, impotent and suffers from severe arthritis. Human genes have been added to cows, sheep, rabbits, mice---and even fish. Scorpion poison genes have been added to cabbages, spider genes to goats---the list is almost endless. We urgently need the technology to cure disease and to feed the world, but its abuse to create, say, designer families for tomorrow's parents is just one nightmare possibility for the future.

Various laboratories around the world have now `decoded' the entire genetic material of a human. This will one day enable us to say that:

The correct bit for any part of a human can then be cut out and transferred, or be reprogrammed and put back into the cell.

So then, it is also possible to map out every single instruction a virus contains and understand precisely what it does in the cell it affects. Why can't all this remarkable technology produce a cure for AIDS? Consider what happens when the virus bubble touches its target cell.

The surface of HIV is specially shaped so that it only fits onto a very small range of cells in the body. The flu virus latches onto cells in the nose, while HIV mainly latches onto one particular type of white cell (CD4 + T-lymphocyte), some brain cells, and one or two others.

When HIV touches the cell and the bubble bursts, the genetic code (RNA) is injected into the cell. Within minutes the code is being read by the cell and the message carried into the cell brain, or nucleus. The message is then added permanently to that cell's `book of life' as DNA. The process took only a few minutes and is complete. The cell looks normal in every way but is now doomed. It may continue to look normal for several years. During this time the white cell continues to travel in the blood looking for invaders while blissfully unaware of the invader within. If the attacked cell divides, the two daughter cells also carry perfect copies of the hidden message. It is likely that the infected cells in semen or vaginal fluids are the main source of HIV transmissions during sex.

Each cell infected by HIV becomes a biological time-bomb travelling in the bloodstream. Millions of them waiting to explode.

One day a particular germ enters the body that this particular cell is geared to deal with. There are thousands of different white cells, all designed to kill different kinds of organisms. It just so happens that out of all the thousands of different infections a person could have caught, this particular one fits the role of this particular cell. It springs into action, programmed by its brain to react. It starts to produce proteins. The cell should help the body turn out finished antibodies that are the exact shape and form to fit the intruding germ and kill it. It's at this point that the effect of the virus is finally revealed. The virus message then overrides the entire cell system and orders a new product to be made: thousands and thousands of HIV messages in genetic code. These are then carried to the outside wall of the cell where each is wrapped and thrown out of the cell. So infected white cells become factories for more virus, instead of factories to help the body make antibodies.

You can see special electron microscope photographs of hundreds of these viruses appearing as little bulges as they poke out from the cell. Eventually they emerge as little round balls, and the cell dies. Millions of virus particles are released into the bloodstream, each one floating in the blood until it touches another CD4 white cell, bursts, injects its message, reprograms the cell, and the process continues.

The trouble is that despite all our modern technology it is hard to detect an infected cell. They look identical from the outside until they are dying. Nor are we able to find the virus easily when it is floating in the bloodstream.

The extraordinary thing about the virus is that its outer bag is formed from your own cell membrane. When it came out from the white cell, it was clothed in cell membrane, so its outer feel is in many ways just like a human cell. It is true that there are some distinguishing marks on the outside of the virus and the body does produce antibodies. However, when the antibody latches on to one of these lumps on the virus coating, the lump can break off, leaving the virus intact just as a lizard sheds its tail.

The problem with HIV is that the body cannot produce antibodies against the virus. On the contrary, almost every person produces antibodies. That is how we test for infection: not by looking for the virus, but by testing for antibodies. The sinister thing is that the virus appears to be to antibodies. No antibodies have yet been found in a human being that are effective in the long term against HIV. That is why a vaccine will be so difficult to find. It is easy to produce antibodies against the virus, but we don't know how to produce one that will prevent infection because we have no natural model from which to work.

The other worrying thing about this virus is its ability to alter its shape. Earlier we saw that antibody-producing cells are specific. An antibody against one organism is only rarely effective against another. If an organism changes its outer coating at all, it is back to the drawing board to make a new antibody. HIV can change shape in subtle ways in the same person over the course of a few months, and a person can be infected with several differently shaped viruses at once, possibly with varying abilities to cause disease. Even worse, HIV occasionally changes its shape radically. We are currently seeing new HIV-like viruses emerging every year or two somewhere in the world. There are at least six HIV strains already. Each of these major variants may have a slightly different ability to infect different groups.

Some strains seem to have lower virulence, as seen in a group infected by blood transfusions from someone with HIV in Australia. Most are still well after years, and the virus cultured seems relatively mild. An increasing number of people are infected with more than one type of HIV. Every time someone is infected, there is a minute chance that radical new changes will occur. As the number of infected people worldwide continues to increase each year, so does the risk of new strains emerging.

The common cold virus is also unstable. That is why we are always getting colds. I probably have antibodies in my blood now to fifty or a hundred different shaped cold viruses. By the time one of those viruses has infected people between here, North America, Japan, Korea, India, Greece and back again, its shape has changed so much that I can catch the same cold all over again. That is why we are light years away from a vaccine against the common cold.

The flu virus is also unstable, but less so. We can usually reckon on two or three different viruses causing most flu for a year or so before changing. We spot the new ones, make a vaccine, and give it to people each year. This annual vaccine has never been popular. Why? Because it often gives people a mild dose of the very flu they were hoping not to catch in the first place, and also because protection only lasts until the virus mutates.

Even if---and a big if---we could create a new vaccine radically different from any other we have ever made, one that somehow could make the body produce antibodies that latch on to any kind of HIV, whatever its shape, there is the worry at the back of people's minds that it could have some serious side effects.

Vaccination of animals against viruses similar to HIV made some of the animals ill. A shortage of chimpanzees and lack of a true animal model for HIV infection mean that animal testing does not tell us much. Vaccines have to be tested at an early stage on humans. Even if vaccines do not give people AIDS, there is the possibility that they might get ill more quickly if infected later. One reason for this is the suggestion that antibodies against HIV may help destroy infected white cells that were otherwise circulating quite harmlessly in the bloodstream. The immune defences of the body against HIV may actually be part of the reason for illness developing.

Imagine giving 10,000 New York school children the new vaccine. How many years do you think it would take before we could be 100% sure that none of them would ever go on to develop problems with the vaccine? The answer is probably five to fifteen years because that is the time scientists now think it can take to develop AIDS. Testing of vaccines requires human guinea pigs. On whom are we going to try it? The answer is that trials are being planned to take place in countries like Uganda. This raises big ethical questions, especially as those vaccinated may think they are now protected. First generation vaccines do not work, although they do give us useful information.

There is the possibility that we could make millions of virus particles without the damaging genes inside. This should be safe but may not be effective. Damaged virus particles tend to produce a very poor immune response and are usually very poor vaccines. Almost all the effective vaccines we possess depend on a milder form of the virus actually infecting the body. Polio vaccine is an example. But there is no milder form of AIDS that we dare risk giving people.

Attempts have been made to take a mild virus used in another vaccine (called `vaccinia') and change it so the outside looks like HIV but is relatively harmless. However, as we have seen, the virus may still turn out to be immune to the antibodies produced. Any vaccine, whether effective or not, will cause all those vaccinated to give `positive' test results, making detection of infection more difficult in those vaccinated.

So then, in summary, we are a long way from a widely available, effective vaccine. In the meantime you will continue to read of countless spectacular claims. Even if a vaccine existed today that was 100% safe and reasonably effective, it would probably take five years to become widely available at reasonably low cost. When it does come, it will almost certainly be useless at treating those millions already infected. However, work is also continuing into different kinds of vaccines which might help an infected person fight infection.

Our only other hope lies in a drug that could destroy viruses in the body. We have none that is effective. For forty years we have searched in vain for a single drug that would work well against a virus without killing the person who takes it. When such a drug appears it will almost certainly cure polio, chickenpox, flu, and a host of other diseases from which our only protection at the moment is vaccination. We will undoubtedly find such a drug one day but it is a long, long way off. How do you kill something that does not breathe, does not need food, does not live and never dies?

1.´Before it touches a cell and its genetic code is injected through the cell wall.

2.´When the genetic code has been unravelled inside the cell and the message is being transferred to the cell brain (nucleus) using a special enzyme called `reverse transcriptase'.

All the newspaper reports of so-called `AIDS wonder drugs' over the next few years will fall into one of these groups.

Attempts have even been made to flood the bloodstream with small pieces of cell wall (CD4) so the viruses are unable to touch living CD4 white cells. Another method being tried is to inject antibodies (`neutralising') from HIV-positive people to give extra protection to people with AIDS.

Others are now looking closely at the virus to try to find any important piece of `machinery' which is unique to virus production and cannot be found in a normal human cell. Machines in cells are called enzymes.

Enzymes are what are found in biological washing powders. We understand what they do very well. Like antibodies they are very specific indeed and each enzyme is capable of only one thing. Enzymes either split large molecules into two smaller ones---which is how they loosen dirt in clothing---or take two smaller ones and join them together. There is a particular enzyme that reads the genetic code of HIV to form the message that reprograms the cell. It is called `reverse transcriptase'. The body does not usually make it, and only viruses use it. If we could find a way of jamming it effectively without bad side effects, we could prevent viruses from reprogramming cells.

We are able to jam various other enzymes in the body. For example, aspirin and arthritis drugs jam an enzyme which makes the most painful substance known to man: prostaglandin. This is produced whenever cells are injured in the body. Nerves are irritated by it and fire thousands of electrical impulses which your brain understands as pain. By jamming this enzyme, prostaglandins are reduced and pain is lessened.

There would be one terrible problem with all such potential drugs. If they can be found, they will have to be taken for life. If some cells in the body are already infected, then a drug preventing entry of new viruses into unaffected cells will need to be taken until every reprogrammed cell and its descendants are dead---which could take fifteen years or longer. If we stopped the drug after ten years and a single reprogrammed white cell were to be activated to make more virus particles, the disease could start progressing all over again. This applies also to drugs preventing reprogramming, virus manufacture, or budding from the cell.

Almost all drugs have side effects and this particular range of drugs has more than its fair share of them. Zidovudine (AZT), for example, which works by jamming the enzyme reverse transcriptase, is also a poison to the bone marrow of the body which produces all your blood cells. You can die from taking too much Zidovudine for too long, and Zidovudine-resistant strains seem to be developing rapidly. Likewise there is an entire family of other drugs called HIV-protease inhibitors. But they also are toxic, and dangerous to use even in experienced hands with all the backing of a well equipped laboratory. Every year new substances are developed and tried in ever-changing combinations and dosages. And survival of people with HIV on these drugs is improving all the time. The effects can be dramatic. Many AIDS wards in wealthy nations have closed as people with HIV are now living longer and healthier lives. But it is not an easy road, and even with new discounts for poorer nations and some factories making medicines unofficially, the prices are still far too high for most people. But even of they were almost free, the drugs themselves could easily kill people unless their use is properly supervised.

Every drug currently being tested has either been found to be poisonous to some degree or other or to have little or no anti-viral effect. In fact, some are so obviously dangerous that the only way a licence can be obtained to give them to human beings at all is because it is on the strictest understanding that all the `human guinea pigs' are going to die soon anyway from AIDS so a death from the drugs is less serious, even if the hope of cure is remote.

The United States federal government is usually extremely strict on new drugs. Drugs have to be tried on vast numbers of animals for years before they can be tried on humans. The United States federal government has never approved so many half-developed products so quickly, propelled by a ghastly sense of urgency for the million or more United States citizens already infected. The same is likely to happen in many other nations.

So the drugs currently being tried are usually suitable only for those already affected by AIDS, and while some may be suitable for those who have only become infected, they are completely unsuitable for giving to the whole nation.

However, as doctors are now seeing such a large proportion of those infected go on to develop AIDS, the pressure is growing to try using these drugs on more and more people at an earlier stage.

Drug companies are pouring billions of dollars into research to find better treatments and much less into vaccines. With a lot less work they can rush through testing and licensing and bring a new drug onto the market. Advertising is unnecessary. Media hype does most of it, and pressure becomes irresistible from patients who are desperate for any hope of cure. Doctors and governments are forced into using drugs which are very expensive---possibly $4,000 per patient---but may hardly work at all and may actually make the patient worse.

Of course we need research trials but they need to be carefully regulated. You can spend millions on a treatment for 500--1,000 patients, or maybe for the same money get 500 full-time health educators on the road into schools, clubs, colleges, factories and offices, preventing maybe 20,000 or more extra AIDS deaths a year. New treatments available in many industrialised nations have increased the cost of caring for someone with AIDS from diagnosis to death.

Vaccines are a different matter altogether: they are very complex to make and many doubt we will ever be able to make one for AIDS that works and is safe. A long period of investment is required over five to ten years before the drug company that develops a vaccine is likely to earn any money. Even if a company creates an effective vaccine, there is a risk of financial ruin if the vaccine turns out to have serious side effects. In the United States, public liability laws and the vast size of lawsuit claims make drug companies vulnerable to bankruptcy if they market something which turns out to be unsafe. As a result, a new Bill has been introduced to US Congress designed to protect researchers and manufacturers from liability in testing AIDS vaccines.

AIDS is big business and many other organisations stand to gain or lose millions of dollars over what happens. A furious argument over who first discovered the AIDS virus took place between French and American scientists. At stake were world rights to royalties from every blood test for AIDS. The row took years to resolve.

Some companies also fear that they would have to make their new product available `at cost' if it turned out to be a wonder cure or an effective vaccine. Public reaction would be great if profits were seen to be made out of tragedy.

Governments need to look at this urgently. No one expects drug companies who operate on behalf of shareholders to go bankrupt in the public interest. They need to be reasonably sure of a return, or if the risks of heavy losses are too large, they need some kind of financial inducement such as low taxation on profits from AIDS vaccines. Failure to address this fundamental issue could set back progress by another couple of decades.

Unfortunately, in the absence of large numbers of volunteers for vaccines in places like the UK, trials are taking place in Uganda, Rwanda, Brazil and Thailand. One might question the ethics of this. The vaccines being used today are useless at preventing AIDS. They produce a degree of immune response, but are only a very first step. Yet in a developing country, an injection of `the latest experimental vaccine' may well create a false sense of security in those taking part in the study. The result could be their deaths.

The vaccines are so unproven, and have such a high risk of potential side effects that it is highly unlikely that parents of children or teenagers in developed countries would want to volunteer members of their family. So are we so sure it is right to proceed in other nations? It can be argued that no adult takes part without giving consent, but it is easy to underestimate the huge faith many villagers place in a Western doctor with high-tech equipment offering the very latest in medical research. At the moment there is nothing to stop someone in a country like Canada or the UK from going over to Africa and doing research there which would be illegal at home. There are huge ethical issues here tied up with inequality of resources and exploitation of developing nations.

Most vaccines so far have been made using `recombinant' genetic engineering. Cells are programmed to make millions of harmless virus fragments which are then injected into people. Antibodies to the fragments should then cross-react with intact infectious HIV. The World Health Organisation is worried that a vaccine might emerge which is very expensive and works only against certain strains in specific areas, useless and unaffordable to developing countries.

The World Health Organisation is now encouraging the development of an infectious non-lethal form of HIV as a vaccine, similar to the vaccine for polio.

There are many examples where people may be making money out of AIDS in various ways. Pacific Dunlop (condoms and surgical gloves) profits grew by 31% in six months of a single year due to the AIDS scare.

There is a fascinating possibility that by 2010 scientists and doctors will be able to program back to normal any cell that has already been reprogrammed by a virus. Suppose a cell has been taken over by a virus and the book of life is now altered. In the laboratory they painstakingly write a new message and put it into genetic code. Then they (somehow) place the new code into an empty virus bag. The test-tube virus is now allowed to touch a white cell. It enters and releases the new message which programs back the book of life so it reads normally.

If you are familiar with computers, it is a bit like recreating a corrupt disc. We are a long way from this, not least because most viruses get cells to produce a special chemical called interferon as soon as they have entered, preventing a second virus from entering the same cell, whether a wild one or a test-tube virus.

A major step forward in human reprogramming was taken in 1990, with children who had adenosine deaminase deficiency. This gene defect is something children are born with and means white cells fail to work properly. The result is an illness like AIDS, with early death.

In a remarkable breakthrough, scientists at the US National Institute of Health located the correct gene, inserted it into viruses built in the laboratory, removed defective white cells from the child, infected the cells to program them back to normal, and then replaced the cells. The child was cured - but only for s short time. Others have carried the work on and in 2002 the result was a permanent cure for a child. To do the same in HIV-infected white cells would mean overcoming the interferon locking system HIV activates once inside a cell, designed to prevent other viruses from entering.

Some have suggested that AIDS is the result of a laboratory accident. HIV was made, they say, in a search for new germs for use in wartime and escaped, or was tried out on a few human guinea pigs and spread wildly across the world.

Although we now possess the means to make viruses far more deadly than HIV, we know that HIV virus first appeared at least as far back as the early 1970s and probably as early as the 1950s, at a time when such technology did not exist. Similar naturally-occurring viruses are common in some animals in some countries and have probably been around in one form or another for centuries.

Twenty years ago we hardly understood anything about viruses and could not even locate the human code for insulin, let alone anything else. It is extremely unlikely that this virus was first made in the laboratory, although it is conceivable that it mutated in a laboratory from an animal virus used to infect human cells in a test-tube experiment.

When you read a newspaper report, take great care. Medical journals are full of papers which contradict others published only a month or two before. This happens because some studies are badly designed or have very few patients in them. If you throw two dice three times and get three sixes, two ones and a three, you could write a little report saying that you conclude that the dice contains lots of sixes, no twos, and no fours or fives. Everyone would laugh at you because they can pick up the dice and look at them. So what went wrong with your research? You threw the dice too few times to comment and you failed to understand how dice work.

Now if, on the other hand, you threw the dice 10,000 times and half the time they came up with sixes, you might correctly conclude that the pair of dice behave as if they are weighted. If you wrote a newspaper article telling people that all dice from a particular shop are weighted people might believe you---particularly when they hear you threw the dice 10,000 times. You and they would be wrong. How can you generalise about all dice when you tested only two?

You may think these illustrations are an insult to your intelligence, but research workers all over the world make classic blunders every day in the same way. You may not think it possible, but it is.

Take the pill, for example. A very effective contraceptive---but is it safe? Every now and then there is a large increase in the number of pregnancies, many of which unfortunately are ended by abortion. These usually follow some report or other from somewhere in the world that the pill may cause some rare cancer or problem with blood or whatever.

Even if the reports are true---and they are often contradicted by others published months before or after but reported in the press---there is a vital fact missing. None of the reports points out that to be pregnant carries a risk to life. A small risk, but a risk nonetheless. Abortion also carries a risk. The risk to most women is far less from continuing to use the pill than from changing to the notoriously unreliable condom with the possibility of a new unwanted pregnancy.

So then, how do we assess the newspaper scoops on new wonder drugs? Ask yourself what the drug does. Where does it act on our scheme of things earlier in the chapter? What are the risks of taking it and how long do you need to take it? How many patients has it been tried on and how many of them have died? Have the results been published in a reputable scientific journal? Many so-called treatments turn out to be elaborate hoaxes or frauds. Recently a woman was jailed for providing a useless preparation for a fee. People feel better after eating chocolate if you tell them it contains a wonder drug. This is called the placebo effect. Did these patients know they were being given a wonder drug? If they did, then no wonder they reported feeling better. Your own doctor will be able to advise you on these things. The vast majority of so-called wonder drugs are nothing of the sort, so do not be too disappointed by the negative reaction of your doctor when you show him a press clipping.

When several research papers say the same thing, when each study contains a large number of people with objective results, eg, numbers still alive after five years, then we can start to feel more confident.

Several new approaches have been developed, all of which are highly experimental, yet could offer hope for the future.

Using anti-HIV drugs in combination, so that the dose of each is kept low, side effects are reduced and the virus is hit hard. This approach may also help prevent drug resistance developing in new virus mutations, although early results have been disappointing.

Liposomes are protein bags similar to ones which occur naturally in the body. They fuse with cell walls, so the contents of the liposome (genes or medication) end up inside the cell. This could be helpful in the future, and is becoming a method of delivering new genes to the lungs of people with cystic fibrosis.

This covers a very large number of different approaches, all designed to help the body fight HIV by adding new genes to human cells. These genes can be designed to help cells block infection, or to help prevent virus multiplication.

This approach uses another relatively harmless virus to control HIV. For example, scientists have found a human herpes virus (HHV7) that only targets CD4 cells, the same ones that HIV infects. When CD4 cells are occupied by HHV7, there is some evidence that HIV is prevented from access. Inactivated HHV7 shows some effect too. There is a possibility then of a live vaccine one day: a mild virus targeting CD4 cells, spreading in the same way as HIV

There is some evidence that many dying white cells are destroyed not by HIV directly, but by the body's own defences which have been made aggressive by HIV. For example, an attack on infected white cells can easily damage `innocent' uninfected cells. Indeed, one part of the HIV structure looks and feels very similar to part of a CD4 cell, so a reaction against HIV could also wipe out white cells directly. It might seem a strange approach in someone with an immune deficiency, but there may be a rationale in some cases in the future to dampen down another part of the immune system using drugs, in order to keep someone well. It all depends which bit of the immune system is dampened down. As we have seen, HIV damages just one part. The rest functions normally, or is even overactive.

We know the cancerous Kaposi's sarcoma is caused by HIV operating together with another agent we have yet to identify. It is a serious condition in people with AIDS and a common cause of death. It seems that HIV makes some white cells overactive so they produce a large amount of a chemical stimulant called cytokine. As a result, cells lining small blood vessels begin to divide and the sarcoma develops. By blocking cytokine production it may be possible to help prevent Kaposi's sarcoma.

For those seeking to avoid sexual infection with HIV, there is an urgent need to develop a new spermicidal cream which is highly active in destroying HIV. This could be used in addition to a condom.

In summary, then, HIV infection is highly complex, involving new, dangerous genes being added to white cells. As gene technology advances rapidly we may hope to see real progress towards a safe, effective, low-cost vaccine or cure. However, the advances being made at present are painfully slow, despite a vast global research effort. This must focus our energy all the more urgently on prevention.

Having seen what a virus is, and how HIV enters and destroys a cell, we can now begin to look at what happens to the body when large numbers of these cells start to die.