HIV stands for Human Immunodeficiency Virus. Like all viruses, HIV cannot grow or reproduce on its own. In order to make new copies of itself it must infect the cells of a living organism.
What does HIV look like?
HIV and CD4+ cell
In this computer generated image, the large object is a
human CD4+ white blood cell, and the spots on its surface
and the spiky blue objects in the foreground
represent HIV particles.
Outside of a human cell, HIV exists as roughly spherical particles (sometimes called virions). The surface of each particle is studded with lots of little spikes.
An HIV particle is around 100-150 billionths of a metre in diameter. That's about the same as:
* 0.1 microns
* 4 millionths of an inch
* one twentieth of the length of an E. coli bacterium
* one seventieth of the diameter of a human CD4+ white blood cell.
Unlike most bacteria, HIV particles are much too small to be seen through an ordinary microscope. However they can be seen clearly with an electron microscope.
HIV particles surround themselves with a coat of fatty material known as the viral envelope (or membrane). Projecting from this are around 72 little spikes, which are formed from the proteins gp120 and gp41. Just below the viral envelope is a layer called the matrix, which is made from the protein p17.
HIV structure
The proteins gp120 and gp41 together make up the spikes
that project from HIV particles, while p17 forms the matrix
and p24 forms the core.
The viral core (or capsid) is usually bullet-shaped and is made from the protein p24. Inside the core are three enzymes required for HIV replication called reverse transcriptase, integrase and protease. Also held within the core is HIV's genetic material, which consists of two identical strands of RNA.
What is RNA?
HIV belongs to a special class of viruses called retroviruses. Within this class, HIV is placed in the subgroup of lentiviruses. Other lentiviruses include SIV, FIV, Visna and CAEV, which cause diseases in monkeys, cats, sheep and goats. Almost all organisms, including most viruses, store their genetic material on long strands of DNA. Retroviruses are the exception because their genes are composed of RNA (Ribonucleic Acid).
RNA has a very similar structure to DNA. However, small differences between the two molecules mean that HIV's replication process is a bit more complicated than that of most other viruses.
How many genes does HIV have?
HIV has just nine genes (compared to more than 500 genes in a bacterium, and around 20,000-25,000 in a human). Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles. The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease.
At either end of each strand of RNA is a sequence called the long terminal repeat, which helps to control HIV replication.
HIV life cycle
Entry
A scientific video about the process of HIV cell entry.
HIV can only replicate (make new copies of itself) inside human cells. The process typically begins when a virus particle bumps into a cell that carries on its surface a special protein called CD4. The spikes on the surface of the virus particle stick to the CD4 and allow the viral envelope to fuse with the cell membrane. The contents of the HIV particle are then released into the cell, leaving the envelope behind.
Reverse Transcription and Integration
Once inside the cell, the HIV enzyme reverse transcriptase converts the viral RNA into DNA, which is compatible with human genetic material. This DNA is transported to the cell's nucleus, where it is spliced into the human DNA by the HIV enzyme integrase. Once integrated, the HIV DNA is known as provirus.
Transcription and Translation
HIV provirus may lie dormant within a cell for a long time. But when the cell becomes activated, it treats HIV genes in much the same way as human genes. First it converts them into messenger RNA (using human enzymes). Then the messenger RNA is transported outside the nucleus, and is used as a blueprint for producing new HIV proteins and enzymes.
Assembly, Budding and Maturation
HIV budding from a cell
This electron microscope photo shows newly formed HIV particles budding from a human cell.
Among the strands of messenger RNA produced by the cell are complete copies of HIV genetic material. These gather together with newly made HIV proteins and enzymes to form new viral particles, which are then released from the cell. The enzyme protease plays a vital role at this stage of the HIV life cycle by chopping up long strands of protein into smaller pieces, which are used to construct mature viral cores.
The newly matured HIV particles are ready to infect another cell and begin the replication process all over again. In this way the virus quickly spreads through the human body. And once a person is infected, they can pass HIV on to others in their bodily fluids.
HIV types, subtypes groups and strains
Introduction to HIV types, groups and subtypes
HIV is a highly variable virus which mutates very readily. This means there are many different strains of HIV, even within the body of a single infected person.
Based on genetic similarities, the numerous virus strains may be classified into types, groups and subtypes.
What is the difference between HIV-1 and HIV-2?
There are two types of HIV: HIV-1 and HIV-2. Both types are transmitted by sexual contact, through blood, and from mother to child, and they appear to cause clinically indistinguishable AIDS. However, it seems that HIV-2 is less easily transmitted, and the period between initial infection and illness is longer in the case of HIV-2.
Worldwide, the predominant virus is HIV-1, and generally when people refer to HIV without specifying the type of virus they will be referring to HIV-1. The relatively uncommon HIV-2 type is concentrated in West Africa and is rarely found elsewhere.
How many subtypes of HIV-1 are there?
The strains of HIV-1 can be classified into four groups: the "major" group M, the "outlier" group O and two new groups, N and P. These four groups may represent four separate introductions of simian immunodeficiency virus into humans.
HIV types, groups and subtypes
The different levels of HIV classification.
Group O appears to be restricted to west-central Africa and group N - a strain discovered in 1998 in Cameroon - is extremely rare. In 2009 a new strain closely relating to gorilla simian immunodeficiency virus was discovered in a Cameroonian woman. It was designated HIV-1 group P.1 More than 90% of HIV-1 infections belong to HIV-1 group M and, unless specified, the rest of this page will relate to HIV-1 group M only.
Within group M there are known to be at least nine genetically distinct subtypes (or clades) of HIV-1. These are subtypes A, B, C, D, F, G, H, J and K.
Occasionally, two viruses of different subtypes can meet in the cell of an infected person and mix together their genetic material to create a new hybrid virus (a process similar to sexual reproduction, and sometimes called "viral sex").2 Many of these new strains do not survive for long, but those that infect more than one person are known as "circulating recombinant forms" or CRFs. For example, the CRF A/B is a mixture of subtypes A and B.
The classification of HIV strains into subtypes and CRFs is a complex issue and the definitions are subject to change as new discoveries are made. Some scientists talk about subtypes A1, A2, A3, F1 and F2 instead of A and F, though others regard the former as sub-subtypes.
What about subtypes E and I?
One of the CRFs is called A/E because it is thought to have resulted from hybridization between subtype A and some other "parent" subtype E. However, no one has ever found a pure form of subtype E. Confusingly, many people still refer to the CRF A/E as "subtype E" (in fact it is most correctly called CRF01_AE).3
A virus isolated in Cyprus was originally placed in a new subtype I, before being reclassified as a recombinant form A/G/I. It is now thought that this virus represents an even more complex CRF comprised of subtypes A, G, H, K and unclassified regions. The designation "I" is no longer used.4
Where are the different subtypes and CRFs found?
The HIV-1 subtypes and CRFs are very unevenly distributed throughout the world, with the most widespread being subtypes A and C.
* Subtype A and CRF A/G predominate in West and Central Africa, with subtype A possibly also causing much of the Russian epidemic.5
* Historically, subtype B has been the most common subtype/CRF in Europe, the Americas, Japan and Australia. Although this remains the case, other subtypes are becoming more frequent and now account for at least 25% of new HIV infections in Europe.
* Subtype C is predominant in Southern and East Africa, India and Nepal. It has caused the world's worst HIV epidemics and is responsible for around half of all infections.
* Subtype D is generally limited to East and Central Africa. CRF A/E is prevalent in South-East Asia, but originated in Central Africa. Subtype F has been found in Central Africa, South America and Eastern Europe. Subtype G and CRF A/G have been observed in West and East Africa and Central Europe.
* Subtype H has only been found in Central Africa; J only in Central America; and K only in the Democratic Republic of Congo and Cameroon.
Are more subtypes likely to "appear"?
It is almost certain that new HIV genetic subtypes and CRFs will be discovered in the future, and indeed that new ones will develop as virus recombination and mutation continue to occur. The current subtypes and CRFs will also continue to spread to new areas as the global epidemic continues.
The implications of variability
Does subtype affect disease progression?
A study presented in 2006 found that Ugandans infected with subtype D or recombinant strains incorporating subtype D developed AIDS sooner than those infected with subtype A, and also died sooner, if they did not receive antiretroviral treatment. The study's authors suggested that subtype D is more virulent because it is more effective at binding to immune cells.6 This result was supported by another study presented in 2007, which found that Kenyan women infected with subtype D had more than twice the risk of death over six years compared with those infected with subtype A.7 An earlier study of sex workers in Senegal, published in 1999, found that women infected with subtype C, D or G were more likely to develop AIDS within five years of infection than those infected with subtype A.8
Several studies conducted in Thailand suggest that people infected with CRF A/E progress faster to AIDS and death than those infected with subtype B, if they do not receive antiretroviral treatment.9
Are there differences in transmission?
It has been observed that certain subtypes/CRFs are predominantly associated with specific modes of transmission. In particular, subtype B is spread mostly by homosexual contact and intravenous drug use (essentially via blood), while subtype C and CRF A/E tend to fuel heterosexual epidemics (via a mucosal route).
Whether there are biological causes for the observed differences in transmission routes remains the subject of debate. Some scientists, such as Dr Max Essex of Harvard, believe such causes do exist. Among their claims are that subtype C and CRF A/E are transmitted much more efficiently during heterosexual sex than subtype B.10 11 However, this theory has not been conclusively proven.12 13
More recent studies have looked for variation between subtypes in rates of mother-to-child transmission. One of these found that such transmission is more common with subtype D than subtype A.14 Another reached the opposite conclusion (A worse than D), and also found that subtype C was more often transmitted that subtype D.15 A third study concluded that subtype C is more transmissible than either D or A.16 Other researchers have found no association between subtype and rates of mother-to-child transmission.17 18 19 20
Is it possible to be infected more than once?
Until about 1994, it was generally thought that individuals do not become infected with multiple distinct HIV-1 strains. Since then, many cases of people coinfected with two or more strains have been documented.
All cases of coinfection were once assumed to be the result of people being exposed to the different strains more or less simultaneously, before their immune systems had had a chance to react. However, it is now thought that "superinfection" is also occurring. In these cases, the second infection occurred several months after the first. It would appear that the body's immune response to the first virus is sometimes not enough to prevent infection with a second strain, especially with a virus belonging to a different subtype. It is not yet known how commonly superinfection occurs, or whether it can take place only in special circumstances.21 22
Do HIV antibody tests detect all types, groups and subtypes?
Initial tests for HIV are usually conducted using the EIA (or ELISA) antibody test or a rapid antibody test.
EIA tests which can detect either one or both types of HIV have been available for a number of years. According to the US Centers for Disease Control and Prevention, current HIV-1 EIAs "can accurately identify infections with nearly all non-B subtypes and many infections with group O HIV subtypes."23 However, because HIV-2 and group O infections are extremely rare in most countries, routine screening programs might not be designed to test for them. Anyone who believes they may have contracted HIV-2, HIV-1 group O or one of the rarer subtypes of group M should seek expert advice.
Rapid tests - which can produce a result in less than an hour - are becoming increasingly popular. Most modern rapid HIV-1 tests are capable of detecting all the major subtypes of group M.24 Rapid tests which can detect HIV-2 are also now available.25
What are the treatment implications?
Although most current HIV-1 antiretroviral drugs were designed for use against subtype B, there is no compelling evidence that they are any less effective against other subtypes. Nevertheless, some subtypes may be more likely to develop resistance to certain drugs, and the types of mutations associated with resistance may vary. This is an important subject for future research.
The effectiveness of HIV-1 treatment is monitored using viral load tests. It has been demonstrated that some such tests are sensitive only to subtype B and can produce a significant underestimate of viral load if used to process other strains. The latest tests do claim to produce accurate results for most Group M subtypes, though not necessarily for Group O. It is important that health workers and patients are aware of the subtype/CRF they are testing for and of the limitations of the test they are applying.
Not all of the drugs used to treat HIV-1 infection are as effective against HIV-2. In particular, HIV-2 has a natural resistance to NNRTI antiretroviral drugs and they are therefore not recommended. As yet there is no FDA-licensed viral load test for HIV-2 and those designed for HIV-1 are not reliable for monitoring the other type. Instead, response to treatment may be monitored by following CD4+ T-cell counts and indicators of immune system deterioration. More research and clinical experience is needed to determine the most effective treatment for HIV-2.26
What are the implications for an AIDS vaccine?
The development of an AIDS vaccine is affected by the range of virus subtypes as well as by the wide variety of human populations who need protection and who differ, for example, in their genetic make-up and their routes of exposure to HIV. In particular, the occurrence of superinfection indicates that an immune response triggered by a vaccine to prevent infection by one strain of HIV may not protect against all other strains. The effectiveness of a vaccine is likely to vary in different populations unless some innovative method is developed which guards against many virus strains.
Inevitably, different types of candidate vaccines will have to be tested against various viral strains in multiple vaccine trials, conducted in both high-income and developing countries.
Animal testing (also known as vivisection) elicits strong opinions from both those for and those against the practice. Its role in developing HIV treatments and AIDS vaccines is no less controversial.
Developing therapeutic and diagnostic products for use in humans is a long and complex process. With HIV infection, the search for effective drugs and vaccines has proven particularly difficult, as HIV is exceptionally good at changing its structure and evading destruction. In an ideal world, scientists would be able to test thousands of different compounds on human participants to see if any cured, treated or vaccinated them against HIV. However, to do this would be both highly time consuming and dangerous, as most compounds would not be effective, and some might cause illness or even death.
Researchers therefore often use animals to help them test the efficacy of drugs and vaccines, and to make sure that these products are safe. There are of course many ethical implications to animal experimentation, and many people are strongly opposed to the use of animals in any sort of experiment or study that may cause them distress or harm. So is it really necessary to use animals in the production of HIV drugs and vaccines? And are there any alternatives to animal testing?
Why are tests performed on animals?
There are three reasons why animals may be used in scientific experimentation. The first is to ensure the safety of new drugs and other pharmaceutical products. The second is to see whether such products might be effective in humans. The third is for general research into the biology of an animal, or the function and action of certain diseases within its body.
Safety trials
In many countries it is a legal requirement that all drugs and vaccines (not just for HIV) are tested on animals to ensure safety. In the United Kingdom for example, the Medicines Act of 1968 1 states that all new pharmaceutical products must be tested on at least two different species of live mammal, one of which must be a large non-rodent. This legislation was introduced shortly after the discovery that the drug Thalidomide could cause serious physical deformities in babies born to mothers who had taken it during pregnancy. Thalidomide was not thoroughly tested on animals (particularly pregnant animals) before it was prescribed to women, and this case is the root of many countries’ animal testing safety laws today.
Thousands of mice and other small rodents are used in animal experiments every year
Thousands of mice and other small rodents are used in animal experiments
every year
Animal safety tests usually come at the end of a long process of safety data collection that may include testing the product ‘in vitro’ (i.e. in a test-tube) and using a computer program to simulate what might happen to the drug inside the body. The regulations on what safety data is required for a new product vary from country to country (and also from drug to drug), but most drug authorities require all three types of data - animal, in vitro and computer- generated - for trials to be allowed to continue.
All this means that at some point, all ‘antiretroviral’ (anti-AIDS) drugs will have been tested on animals for safety.
There is an argument however that animals are actually fairly poor substitutes for humans and that some compounds that may well cause no harm to a mouse, could kill a human being. This is particularly the case for drugs that interact with the complex human immune system, such as the anti-inflammatory drug that caused major organ failure in six men involved in a trial at Northwick Park Hospital in London, England in 2006. However, such occurrences are rare.
Efficacy trials
While all drugs and vaccines have to be tested on animals to establish their safety, testing them to establish their effectiveness is a different matter.
HIV is a retrovirus specific to humans (hence the name ‘Human Immunodeficiency Virus’), which means it is not naturally found in any other animal. Some African primates, such as chimpanzees and a few species of monkey, are naturally infected with SIV (Simian Immunodeficiency Virus), which is believed to be the virus from which HIV originated. Chimpanzees can also be artificially infected with HIV in a laboratory. However most monkeys and chimpanzees have very efficient immune responses to SIV (and HIV), and do not develop AIDS, even after many years of infection. This can make it very difficult to assess whether a drug or vaccine actually works, so primates are not used as widely as human substitutes as they once were.
This said, there is one primate still commonly used to conduct efficacy testing: the Rhesus macaque monkey. Because Rhesus macaques originate from Asia, rather than Africa, they have never been exposed to SIV, and thus have no natural immune responses to it. A Rhesus macaque that is infected with SIV will therefore develop AIDS type illnesses in a relatively short time 2.
For this reason (and because they are not an endangered species like some other Asian primates), macaques are often used in HIV research. A few HIV drugs, such as AZT and tenofovir (see our Introduction to Antiretroviral Treatment page for more information about these), have been tested on macaques for efficacy, though stricter rules on the use of primates in animal testing, and greater knowledge of HIV, mean that more modern antiretrovirals are generally only tested on animals for safety reasons.
Vaccine development on the other hand makes extensive use of primates. Because it could be seen as unethical to give a healthy human a vaccine, and then expose them to HIV to see if the vaccine works (if it doesn’t, they’ll end up with HIV), animals can be used as substitutes to establish whether a vaccine is effective or not. This method can also be used to test the usefulness of current AIDS drugs (such as tenofovir) in preventing HIV infection. Such work of course raises significant questions over whether it is any more ethical to give a monkey HIV than a human, when it too may become sick with AIDS and die.
A fundamental problem with using macaques in vaccine research has been that they have different immune systems to humans. This means they cannot be infected with HIV-1 (although they are susceptible to certain strains of HIV-2), however they can be infected with SIV, or an SIV-HIV combination (‘chimeric’ virus) known as SHIV. A drug or vaccine that is effective in Rhesus monkeys infected with SIV or SHIV may not therefore be effective in humans with HIV. Conversely, a drug or vaccine that may be effective in an HIV positive human may be dropped because it appears ineffective in animals. Scientists have now constructed a simian strain of HIV-1 that differs from the human virus by only one gene and mimics early HIV infection, however the infected macaques did not develop AIDS3. Further research on this genetically engineered virus is necessary, however if successful this may make testing vaccines in primates potentially more reliable.
Monkey research has yielded significant discoveries about HIV in recent years4, including major findings that have strengthened understanding of early SIV and HIV infection5.
General research
As well as the testing of new drugs and other products, animals may also be used for more general research that aims to gain a greater understanding of a disease. Rhesus macaques, chimpanzees and even cats (who can get Feline Immunodeficiency Virus) may be used as human substitutes to see how HIV-like viruses operate within the body.
Rhesus Macaques are commonly used in HIV research
Rhesus Macaques are commonly used in HIV research
They can also be used to study natural phenomena such as transmission or disease progression, and the effects of non-therapeutic substances on HIV.
One example would be a study carried out in Rhesus macaques in 2006 6. Scientists looking at the effects of alcohol on SIV found that feeding the monkeys large quantities of alcoholic beverages over a short space of time (effectively making them ‘binge’ drink) could significantly speed up the rate at which HIV progressed to AIDS. This may well lead to a greater emphasis on moderate drinking amongst HIV positive people, and a reassessment of safe levels of alcohol. However, whether the results of this experiment could have been recreated using methods that didn’t involve animals is open to debate.
Can animal testing be justified?
Animal testing is an extremely controversial and hotly debated area, and there are many groups around the world that are strongly opposed to animals being involved in any form of experiment, even if it involves simply keeping them in captivity. Equally, there are groups who say that there is no alternative to animal testing, and that animals have saved many human lives. Some of the scientific and moral arguments for and against animal testing include:
* FOR: Animal testing is justified because of the many human lives that it can save
* AGAINST: There is no firm evidence that animal testing has saved anyone’s life directly, particularly in the case of HIV – most drugs could probably have been developed without the use of animals.
* FOR: Humans are clearly unique amongst animals in our abilities and intellect. Animals do not experience pain and emotion in the same way that we do because they lack language and the power of abstract thought
* AGAINST: An animal’s life is equal to a human’s and we have no right to assume otherwise simply because animals cannot express their pain and suffering in words
* FOR: Animals are the best way to test vaccines, because it would be unethical to give a human a vaccine, and then to try to give them HIV to see if it works.
* AGAINST: It is no more ethical to give an animal a life-threatening illness than it is to give one to a human.
* FOR: SIV-infected chimps and Rhesus macaques are good substitutes for humans, and make drug and vaccine development far more simple
* AGAINST: Monkeys and chimpanzees do not have identical immune systems to humans, and may not respond to drugs or vaccines in the same way. Rhesus macaques also cannot be directly infected with HIV. No HIV vaccine has yet been developed, despite many years of animal involvement.
* FOR: Any differences between animal and human biology are generally known, and can be factored in to experiments
* AGAINST: This overlooks the effect that stress may have on the normal functioning of an animal’s body, which may in turn affect the results of the experiment
* FOR: Not testing new pharmaceutical products on animals is highly dangerous
* AGAINST: Animals are often poor substitutes for humans, and some compounds that may well cause no harm to an animal, could seriously harm a human being. Likewise, a drug that is toxic to the animal it is tested on, may have no toxicity, and even therapeutic benefits in humans.
* FOR: There are no viable alternatives to testing pharmaceutical products for safety on animals. Scientists already use in-vitro studies and computer models, and animal testing comes only after these tests have been performed. If a drug fails either test, it will not be given to animals anyway.
* AGAINST: Studies have suggested that ‘micro-dosing’ (where only a tiny amount of a product is given to a human through the skin) could be a new and very effective alternative to animal experiments 7. The recent news that scientists have grown a small piece of human liver tissue from stem cells could also mean that it may one day be possible to perform initial 'human' safety trials in a lab8.
* FOR: There are very strong laws in place to ensure that distress and pain in animals is kept to an absolute minimum
* AGAINST: Pain and suffering still occur, and simply being in captivity can cause great distress to an animal, just as it would to a human. Plus, animal testing facilities cannot be monitored at all times, so the sort of treatment animals receive on a daily basis can never truly be known.
* FOR: It is a legal requirement that drugs are tested on animals for safety in the majority of countries. Scientists have no choice in this matter.
* AGAINST: Perhaps if laws on the necessity for animal testing were relaxed, or animal safety-testing were banned, it would encourage scientists to develop other methods of testing toxicity that were equally effective. At the moment, they have no incentive to do so, so only a small handful of alternatives are being tested.
* FOR: No scientist wants to cause any more injury to an animal than is strictly necessary. Most scientists build up strong attachments to the animals they use in their experiments.
* AGAINST: This may be the case, but it is also very easy to become blasé about something that you do every day, and forget the pain and suffering your work is inflicting. Animals may well become little more than useful objects of study, rather than live creatures, and this can mean they are treated as disposable rather than indispensable.
What do HIV+ people think of animal testing?
Many HIV positive people condone, or remain neutral on animal testing because they are aware that the drugs they take to keep them alive have very likely been tested on animals at some point in the past.
Could human 'guinea pigs' be viable alternatives to real ones when testing new drugs?
Could human 'guinea pigs' be viable alternatives to real ones when testing new drugs?
In September 2005, six well-known AIDS organisations in the USA got together to form ‘Patient Advocates Against PETA’ (PAAP), a group that opposed the strong anti-animal testing stance of People for the Ethical Treatment of Animals (PETA) 9. Formed of ACT UP DC, ACT UP Southern California, AIDS Healthcare Foundation, AIDS/HIV Health Alternatives, AmASSI and the HIV Incarcerated Task Force, PAAP argued that PETA’s constant high-profile protests were hindering scientists in their search for effective HIV vaccines.
Their work was however opposed by a number of HIV positive individuals, who declared they were strongly opposed to animal testing, and did not condone PAAP’s actions. A consensus amongst HIV positive people themselves on the benefits of animal testing is obviously not very forthcoming.
What is the future for HIV and animal testing?
In recent years, scientists have begun to investigate the possibility of genetically altering the genes of some animals (particularly mice) to give them immune systems that more closely resemble a human’s, and are thus susceptible to HIV infection. Such small animal models could be useful, both for those developing new vaccines, and for those testing drugs for safety, but such work is strongly opposed by those who do not believe that genetically modifying animals is morally right or safe, as well as by those who oppose animal testing altogether.
Another alternative recently proposed is infecting ordinary mice with a chimeric form of HIV, similar to the 'SHIV' used to infect primates. This would allow efficacy trials of drugs and vaccines to be performed on small mammals, which could perhaps be combined with safety trials to reduce the time taken to reach regulatory approval. However, this would potentially increase rather than reduce the number of animals involved in clinical testing.10
Regulations on animal testing have been tightened considerably in recent years, and animals, particularly primates, are used in far fewer experiments than they once were. In most countries (particularly the UK, which has the tightest regulations on the use of animals for science) facilities where animals are held are inspected regularly to ensure that animals are being kept in hygienic, safe and comfortable conditions.
Nonetheless, animal testing is still very strongly opposed by many groups who believe that any form of animal exploitation is wrong. The majority of anti-vivisection groups stage peaceful protests that aim to raise awareness of the harm and pain that animal testing can inflict, and raise support amongst the public for a ban on the practice. However a small minority of animal rights activists have resorted to more extreme tactics, which have included intimidation of those directly involved in experimentation, intimidation of their families, suppliers and business partners, and criminal acts, ranging from harassment and vandalism to blackmail and arson 11, 12, 13.
Unfortunately, while such groups receive substantial media coverage, their extreme actions tend to drown out the messages of more moderate groups, who are simply calling for a reassessment of the law, or greater research and assessment of alternative methods. Their behaviour creates a counter-productive situation, whereby those who conduct experiments on animals become more determined to continue with their work because of the opposition they face, and the government refuses to launch a proper investigation into the current laws in case they are seen as ‘giving in’ to extremists. It also risks portraying all animal rights campaigners as extreme activists and all scientists as cruel animal abusers.
In reality, views on animal testing are not nearly as polarised as this. There are many moderate anti-vivisection groups, just as there are many scientists who would prefer not to test on animals if they had a choice. A meaningful debate between the two may well help to further progress into ending the reliance on animals for safety and efficacy testing, but while the issue remains connected to such controversy and extremism, discussions of this kind seem to be few and far between.
It may be that one day animal research produces a vaccine or a cure for HIV that saves millions of human lives. If this is the case, then some justification can perhaps be found in using animals for our own purposes. Until this time however, anti-vivisectionists need to remain focused on finding alternatives, informing and changing legislation and keeping testing on animals to an absolute minimum. It is only through such positive action that true progress can be made.
Evidence that HIV causes AIDS
Introduction
"AIDS is caused by infection with a virus called human immunodeficiency virus (HIV). This virus is passed from one person to another through blood-to-blood and sexual contact."1
That's the standard explanation of what causes AIDS. But what evidence do scientists have to support this theory? And why do some websites say that the world has got it terribly wrong – that HIV does not cause AIDS at all?
As an independent AIDS organisation founded in 1986, AVERT has taken a keen interest in the ongoing debate about what causes AIDS. As well as investigating the consensus position, we have followed and carefully considered the arguments of the dissident minority who claim that HIV is harmless or even that it might not exist. This topic is vitally relevant to how our organisation works to prevent people developing AIDS and to help those who are suffering.
It is AVERT's considered opinion that the evidence that HIV causes AIDS is abundant and conclusive. This page outlines some of that evidence, while also mentioning how some dissidents have interpreted things differently. In particular, we'll look for proofs of the following:
* AIDS is a new epidemic disease
* AIDS does not occur without HIV
* HIV infection is the only factor that predicts who will develop AIDS
* Surveillance statistics support the HIV theory
* Modern antiretroviral treatment is highly beneficial.
Who doubts that HIV causes AIDS?
By far the most significant scientist to question the HIV/AIDS theory is Professor Peter Duesberg, a virologist at the University of California at Berkeley, who first wrote about this topic in 1987. Throughout the 1990s and into the new millennium, as HIV/AIDS researchers announced many new discoveries and amassed huge volumes of data, Dr Duesberg remained unconvinced. He admits that HIV exists, but he maintains that it is harmless, and that AIDS is caused by non-contagious factors including drug abuse, malnutrition, and even the very drugs used to combat HIV.2
Other dissidents (often called "denialists" by their opponents) include the Perth Group of medical scientists and physicians from Australia. The Perth Group (led by Eleni Papadopulos) claims that nobody has conclusively proven the existence of HIV, so any proof that HIV causes AIDS has no foundation.3
Dissident arguments have received attention from the popular media, as well as from scientific journals. And with the rise of the Internet, alternative views have found a much wider audience, so that scarcely anyone interested in AIDS can have failed to hear of them.
Some of their followers are intrigued by conspiracy theories involving sinister drug companies or government persecution of minority groups. But alternative explanations can also appeal to those diagnosed with HIV or AIDS, who read that their condition might not be fatal, that they shouldn't take toxic drugs, and that unprotected sex poses no risks. Even a few AIDS service organisations have adopted non-HIV viewpoints.4
However, the proportion of scientists who doubt that HIV causes AIDS is tiny, and shows no sign of increasing. Interest in dissident views appears to have dwindled after the excitement surrounding Thabo Mbeki's AIDS panel and the Durban Declaration in 2000. It seems likely that new and better evidence, including the obvious benefits of modern drug treatments, has caused many former-dissidents to change their minds.
What is AIDS?
Before we can begin to look for a cause, we must first work out exactly what type of illness we are talking about.
In early 1981, doctors in New York and California began to report some bizarre new disease outbreaks. In both places, previously healthy young men were showing up with rare illnesses including Kaposi's sarcoma (a kind of tumour) and PCP (a type of pneumonia), which until then had been virtually unheard of among such people. Within months, dozens of similar cases had been reported in 23 American states and in the UK, representing the start of a massive and unprecedented epidemic.5
Doctors soon discovered a distinctive feature of these cases. More than anything else, the men were lacking a specific type of white blood cell, which is essential to a healthy immune system. Normally, people have between 600 and 1,500 "CD4+ cells" (also called T helper cells) in each cubic millimetre of their blood. But the men with the strange new disease typically had very much lower levels. This immune deficiency explained why they were so vulnerable to disease.
The cases were clearly related in time and by population group (initially gay men and injecting drug users). No cause of immune deficiency could be found, but it was clearly not inherited. Scientists therefore grouped together all of these strange new cases under the heading "Acquired Immune Deficiency Syndrome" – or AIDS for short.
In 1982, no-one claimed to know the cause of AIDS, so the first definition was based on the diagnosis of one of 13 rare diseases known to be linked to immune deficiency (including Kaposi's sarcoma and PCP) "occurring in a person with no known cause for diminished resistance to that disease".6 Over the years, the US definition has been refined as hundreds of thousands of similar cases have been documented, sometimes involving other diseases, but always associated with the same distinctive immune deficiency.7 Other definitions have also been developed to suit different situations elsewhere in the world.8
The latest US AIDS definition was created in 1993. Under this definition, someone has AIDS if they have one of 26 specific diseases (28 in children) but no known cause of immune deficiency other than HIV (with some diseases, a positive HIV test is required); or if they have a CD4+ cell count below 200 cells per cubic millimetre of blood, or less than 14% of all lymphocytes, plus a positive HIV test.9
Europe and Canada have similar AIDS definitions to the US, but do not include low CD4+ cell counts.
Problems with the definition?
The definition of AIDS usually requires a positive HIV test. This means that any connection between HIV and AIDS is artificially strengthened because any cases of "HIV-free AIDS" are discounted. In other words, the definition already assumes that HIV causes AIDS, so it can't be used to prove that theory. However, it is possible to redefine AIDS without reference to HIV or even to any other diseases.
The alternative definition of AIDS requires a CD4+ cell count consistently below 200 cells per cubic millimetre of blood, which cannot be explained by any factor other than HIV (such as cancer, malnutrition, radiation or chemotherapy). No HIV test is required.
It turns out that the vast majority of people diagnosed with AIDS fit these criteria. They form a population that barely existed before 1980, but which now numbers hundreds of thousands in the USA and Europe alone. People with such severe immune deficiency are at very high risk of developing serious illnesses and usually die within months (unless they take antiretroviral drugs).10 11 12 We can use this simple, unambiguous definition to test the association between HIV and AIDS.13 14
How can we prove that HIV causes AIDS?
Koch's Postulates
In the nineteenth century, the German scientist Robert Koch developed a set of four "postulates" to guide people trying to prove that a germ causes a disease. Scientists agree that if HIV satisfies all of these conditions with regard to AIDS then it must be the cause of AIDS:15
* Koch 1: The germ must be found in every person with the disease
* Koch 2: The germ must be isolated from someone who has the disease and grown in pure culture
* Koch 3: The germ must cause the disease when introduced into a healthy person
* Koch 4: The germ must be re-isolated from the infected person
Other evidence
Even Koch recognized that in some cases not all of his conditions could be met, so other evidence should also be considered. This is particularly true when the germ is a virus rather than a bacterium.16 Modern scientists are willing to consider a wide range of evidence. In particular, we can ask five key questions:
* Do surveillance statistics show a relationship between HIV and AIDS?
* How well does HIV infection predict illness and death?
* Do drugs designed to combat HIV benefit people with AIDS?
* Are there any credible causes besides HIV?
* What can we learn from Africa?
We'll address these questions after looking at Koch's Postulates.
Koch 1: The germ must be found in every person with the disease
The US Centers for Disease Control and Prevention (CDC) defines a condition called idiopathic CD4+ T-lymphocytopenia, or ICL for short. Someone is diagnosed with ICL if they have a CD4+ cell count below 300 cells per cubic millimeter, or 20% of all T lymphocytes, on at least two occasions, but have no detectable HIV infection, nor any other known cause of immune deficiency (such as cancer therapy). As many dissidents have pointed out, this is essentially a definition of HIV-free AIDS. So just how common is this condition?
In 1993, a CDC task force published the results of an exhaustive survey of ICL in the USA. They had reviewed 230,179 AIDS-like cases reported since 1983 and identified 47 patients with ICL (plus 127 uncertain cases). All of the other people with AIDS who had received an HIV test produced a positive result. What's more, the team closely investigated the ICL cases and discovered that they didn't fit the usual AIDS profile. There were 29 male and 18 female patients, and 39 of them were white (4 others were of Asian descent). In 29 cases, the researchers couldn't fit the people into conventional risk groups for AIDS (homosexual men, haemophiliacs, injecting drug users, and the sexual partners of such groups). Whatever these 47 cases represent, they don't seem to be typical of the massive epidemic that we're interested in.17
The findings of the ICL survey are backed up by large-scale monitoring studies, including the Multicenter AIDS Cohort Study (MACS). During the MACS, scientists monitored the health of 2,713 gay and bisexual men who tested negative for HIV antibodies. Over several years, only one of these men had persistently low CD4+ cell counts, and he was undergoing cancer therapy designed to weaken his immune system. Similar results have been found among blood donors, recipients of blood and blood products, injecting drug users and other groups: severe immune deficiency is virtually non-existent among those who test HIV-negative.18
As Dr Duesberg has pointed out, quite a lot of people (mostly in the early 1980s) have been diagnosed with AIDS in the USA despite never taking an HIV test, and nobody knows whether these people were HIV-positive or not. However, based on the much larger sample of people who have been tested, Koch's first postulate has certainly been satisfied. The only way by which dissidents have been able to come up with significant numbers of HIV-free "AIDS" cases is by using much looser definitions of AIDS. Such definitions include many people with milder immune deficiency, which is generally not fatal.19 20
What about false positive test results?
Diagnosis of infection using antibody testing is one of the best-established concepts in medicine. The World Health Organisation and the US National Institutes of Health agree that modern HIV tests are extremely reliable, and are even more accurate than most other infectious disease tests.21 22
Nevertheless, some dissidents have tried to dismiss the association between AIDS and HIV by claiming that many of those who test positive are not really infected with HIV. In particular, Christine Johnson has listed dozens of conditions reported to have produced false positive reactions on at least one occasion (under particular circumstances, using particular test kits).23
It is true that no test is perfect. However, what the dissidents usually don't mention is how rare the reports of false positive results have been, especially in recent years. Nor do they mention that every person who uses a test kit is trained to spot the telltale signs of a suspicious result, and to keep testing by various methods until no doubt remains. The conditions that cause false positive results are not only very uncommon, but are also typically short-lived, whereas HIV infection does not go away.24 25
The dissident theory cannot satisfactorily explain why scientists have been able to use various techniques to detect the virus itself in virtually everyone with AIDS, as well as in most people with positive antibody test results, as explained in the next section. These methods (including DNA PCR, RNA PCR and viral culture) are not affected by any of the factors said to produce false positive results in antibody testing.
Nor can the alternative theory fully explain why the association between AIDS and antibody test results is so exceptionally strong: virtually everyone with AIDS tests positive, while more than 99% of the US public tests negative. And it cannot explain why the proportion of people testing HIV positive should have increased so dramatically over time. For example, the proportion of South African women testing HIV positive in annual antenatal surveys rose from 0.8% in 1990 to 10.4% in 1995, 24.5% in 2000 and 29.5% in 2004. The age distribution of these data is similar to that of other sexually transmitted infections.26
Koch 2: The germ must be isolated from someone who has the disease and grown in pure culture
Koch required that the germ be isolated from all other material that could possibly cause disease, so that his third and fourth postulates could be properly tested.
In May 1983, Luc Montagnier and his colleagues in France reported the isolation of a virus they named LAV, which infected and killed CD4+ cells. A year later, the American Robert Gallo announced he had isolated a virus called HTLV-III and found a way to grow it in culture. It was later discovered that the two viruses were genetically indistinguishable, and they were renamed HIV.27
Researchers have been able to isolate and culture HIV from most AIDS patients whom they have examined (as well as from many other people with HIV antibodies).28 They have isolated the virus from blood cells, blood plasma, lymph nodes, semen, vaginal fluids, amniotic fluids, bone marrow, brain, cerebrospinal fluid, intestines, breast milk, saliva and urine, and cultured it in various cell types.29 Images taken using electron microscopy and other techniques have shown virus-like particles that have the size, shape, structure, density, proteins and behaviour expected of retroviruses.30 31 32
Techniques developed in the mid-1990s have made it much easier to extract and sequence the complete genetic material (genome) of an isolated virus.33 34 The Los Alamos database now contains hundreds of full-length HIV genomes from around the world, each containing the same nine genes.35 Based on genetic similarities and differences, these sequences have been used to define family trees of HIV types, groups and subtypes as well as hybrids called recombinant forms.36
Whole or partial HIV genomes have been detected in numerous AIDS patients, using a technique called PCR (the same technology is used to find DNA evidence with which to convict murderers or to settle paternity suits, as well as to detect the germs that cause hepatitis, tuberculosis and other diseases). Almost everyone who tests positive for HIV genetic material also tests positive for HIV antibodies, and vice versa, while those who test negative for one thing also lack the other.37 People who have been exposed to the same source of infection contain genetically very similar HIV strains – similar enough for court convictions.38
Scientists have used a standard technique of genetic science called molecular cloning to obtain highly purified HIV. Genetic material extracted using PCR or other techniques has been introduced into bacteria or other cells (usually using phages or plasmids), which then produce many exact copies (clones) of the viral genes. If cloned viral genomes are inserted (transfected) into human cells then they produce a new generation of infectious HIV particles, which are free from contamination.39
Virtually all experts agree that HIV has been isolated according to the most rigorous standards of modern virology, meaning that Koch's second postulate has without doubt been satisfied.
What about the Perth Group?
A small band of Australian scientists and physicians claims that HIV has never been properly isolated. The Perth Group has never said that HIV doesn't exist; rather they say that HIV has never been conclusively proven to exist. They don't trust any HIV tests, because they have not been verified using their "gold standard" of isolated virus. The Group uses the isolation argument to dismiss just about every type of evidence that HIV causes AIDS.40
Virtually all virologists believe that the Perth Group's conditions are unnecessary. They say nobody has ever used such rules to isolate any type of virus, and that other techniques are much more effective. According to the Perth Group's rules, nobody has isolated or proven the existence of the viruses said to cause small pox, influenza, measles, mumps and yellow fever.
Experts argue that the Group's rules are unreasonably demanding and impossible to satisfy fully, even though their main requirements have already been met.41 42 Dr Duesberg is among those who have tried in vain to persuade the Perth Group that HIV definitely exists and has been isolated using the most rigorous methods available.43 44 45
The Perth Group appears to have only two active members: a medical physicist called Eleni Papadopulos-Eleopulos and an emergency physician called Valendar Turner. In late 2006, Papadopulos-Eleopulos and Turner testified in the appeal trial of Andre Chad Parenzee, an HIV-positive man convicted of endangering life by having sex with three women without informing them of his infection. The two witnesses intended to demonstrate that HIV had not been proven to exist; that HIV tests were unreliable; and that there was no evidence of HIV transmission through sex.
The presiding judge concluded that the Perth Group members had no qualifications or practical experience in virology, immunology or epidemiology, and were not qualified to express opinions about the existence of HIV, or whether it had been shown to cause AIDS. The judge found that the pair relied entirely on the work of others, which they often took out of context and misrepresented. Their arguments were found to lack plausibility and cogency, and to have "minimal" probative value. "I am satisfied that no jury would conclude that there is any doubt that the virus HIV exists," said Justice Sulan. "I consider no jury would be left in any doubt that HIV is the cause of AIDS or that it is sexually transmissible."46
Koch 3 and 4: The germ must cause the disease when introduced into a healthy person, and the germ must be re-isolated from the infected person
The third and fourth postulates are much harder to prove. It's considered unethical to deliberately infect someone with pure HIV, so such an experiment has never taken place. However, there is no reason why the transmission has to be deliberate.
There have been three reports of lab workers developing immune deficiency after accidentally exposing themselves to purified, cloned HIV. As mentioned above, such cloned virus is free of all contamination from the original source. None of these people fitted conventional risk groups for the disease. In each case, HIV was isolated from the individual and, by genetic sequencing, was found to be the strain to which they'd been exposed. One of these workers developed PCP and had a CD4+ cell count below 50 cells before starting antiretroviral treatment.47
Still, three examples don't make a totally conclusive proof, so it's worth looking for more evidence.
One line of argument can be based on animal experiments.48 In some studies, chimpanzees deliberately infected with HIV-1 have gone on to develop AIDS-like conditions (though this appears to be rare),49 while HIV-2 has had the same effect on baboons.50 Macaque monkeys have developed AIDS after being infected with a hybrid virus called SHIV, which contains genes taken from HIV.51 And in mice engineered to have a human immune system, HIV produces the same patterns of disease as in humans.52
If we're prepared to bend the rules a bit further, we can look at people who've been infected with non-purified HIV. Such cases at least suggest that AIDS is infectious, though they don't rule out the possibility that more than one germ is involved.
Scientists have documented numerous cases of people developing AIDS after becoming infected with HIV as a result of blood transfusions, drug use, mother-to-child transmission, occupational exposure and sexual transmission. In such cases, they have recorded the development of HIV antibodies (seroconversion) using a series of blood tests, before progression to AIDS. Seroconversion is often accompanied by a mild flu-like illness or swollen glands.53
Until the mid-1990s, nobody claimed that HIV had fulfilled Koch's last two postulates. Even today, the proof is not quite perfect. But most scientists believe the evidence is now strong enough to put the case beyond all reasonable doubt.54
Surveillance statistics
Most countries with high rates of HIV have conducted regular national HIV surveillance studies since the early 1990s. AIDS case reporting began much earlier, in the early 1980s. All of the data are available to the public online.
HIV and AIDS in Thailand, 1984-2000
HIV and AIDS in Thailand, 1984-2000
AIDS case statistics are generally expected to underestimate the scale of AIDS epidemics, especially in African countries, because many cases go unreported. However, it is reasonable to assume that trends in the number of reports should roughly correspond to trends in the overall epidemic.
Of all countries, Thailand has one of the best records of HIV surveillance, with around 70 sites included each year since 1990. Thailand also has relatively good infrastructure for the reporting of AIDS cases. On the right is a graph showing trends in Thai statistics between 1984 and 2000.55
The graph shows that during the 1990s there was a dramatic increase in AIDS case reports. This increase came after a sharp rise in HIV prevalence, with a time lag of a few years (nearly 200,000 HIV tests conducted between 1985 and 1987 produced fewer than 100 positive results).56 Such a time lag is exactly what the HIV theory predicts, because most people are expected to live with HIV for some time before developing AIDS.
Thailand is not unique. Exactly the same pattern can be seen in statistics worldwide, from Albania (where HIV and AIDS are both very rare) to Zimbabwe (where AIDS case reports soared during 1987-95, following the trend in HIV prevalence).57 58
This trend can also be seen within individual countries as regions, cities or population groups with higher HIV prevalence report a higher rate of AIDS.59
How well does HIV infection predict illness and death?
A mountain of evidence shows that much can be predicted from a positive test result. For example:
* Around half of people develop AIDS-defining conditions within 10 years of HIV infection, if they don't take antiretroviral drugs. Only a few do not develop AIDS within 20 years.60 61
* HIV-positive Americans and Canadians are over 1,000 times more likely to develop AIDS-defining diseases (such as PCP and Kaposi's sarcoma) than those who test negative.62 63
* A study in Uganda found that HIV-positive people were 16 times more likely to die over five years than those who tested negative. For those aged 25-34 years old, HIV infection raised the death rate by a factor of 27.64 Numerous other studies have found similar results in Tanzania, Malawi, Rwanda and other parts of Africa.65 66 67 68
* A study of female sex workers in Thailand found the death rate to be over 50 times greater among those who tested positive. All of the positive women died of conditions associated with immune deficiency, compared with none of the negative women.69
* During a 16-year, large-scale monitoring study of homosexual and bisexual men in the US, 60% of HIV-positives died compared with 2.3% of HIV-negatives.70
* In the UK between 1979 and 1992, death rates increased massively among HIV-positive haemophiliacs, but remained unchanged among the rest.71 Similar research in the USA found that HIV-positive haemophiliacs were 11 times more likely to die over a ten-year period, compared with those who tested negative.72
* In a European study of babies born to HIV-positive women, none of those who tested negative developed AIDS, compared to 30% of those who tested positive. By their first birthday, 17% of the HIV-positive babies had died.73 A similar study in Uganda found that more than half of HIV-positive babies died before their second birthdays, compared to one sixth of those who were HIV-negative.74
Alternative theories cannot explain why HIV tests should be so effective at predicting illness and death in so many diverse groups of people from all parts of the world.
It is even possible to predict the likelihood that someone will soon develop AIDS by measuring the amount of HIV in their blood, which is known as "viral load". Such measurements can be made using PCR, branched-DNA signal-amplification (bDNA) or quantitative microculture techniques. For example, the table below - based on a long term study of 1,604 patients - illustrates just how useful bDNA forecasts can be:75
Viral load (RNA copies per millilitre of blood plasma) Proportion of patients developing AIDS within six years
less than 500 5.4%
501-3,000 16.6%
3,001-10,000 31.7%
10,001-30,000 55.2%
more than 30,000 80.0%
Dr Kary Mullis, who invented the PCR process, has questioned its ability to measure viral load. However, his arguments have been theoretical, and are not backed up by large-scale surveys, which have repeatedly shown a clear association between viral load and progression to AIDS (in all parts of the world).76 77 Dr Mullis' objections do not apply to the unrelated bDNA and quantitative microculture techniques. Modern bDNA tests produce very similar viral load counts to modern PCR tests (though this was less true of some earlier models).78 79 As with antibody tests, there is no convincing alternative explanation for why viral load counts should be such useful indicators.
Effective drug treatments
The first drug licensed for fighting HIV was zidovudine, better known as AZT, which gained approval in 1987. Multiple studies found that AZT reduced opportunistic infections and increased CD4+ cell counts and survival among people with AIDS. However, the positive effects of AZT did not last very long, and a major investigation known as the Concorde Study found that people who started taking the drug at an early stage of HIV infection, before the onset of symptoms, received little or no long-term benefit (though neither did they fare any worse).80 81 82
Since the mid-1990s, other types of anti-HIV drugs have also been available, including protease inhibitors, which were designed specifically to target HIV proteins.83 It has been found that when different drugs are taken together, they bring much longer-lasting benefits than AZT alone.
Numerous large-scale, controlled studies have consistently shown that the right combination of drugs can dramatically reduce incidence of AIDS and death. One drug is better than none, and two is better than one, but a combination of three drugs (from two different classes) is much better still. Virologists explain that this is because HIV finds it a lot harder to evolve resistance to several drugs at the same time. Modern three-drug combinations reduce the risk of AIDS and death by over 80%.84 85 86 87
Many recent studies in Africa have found that treatment is just as effective there as it is in Europe and America.88
In most people, the drugs cause a sharp fall in viral load. However, some patients do not experience such an effect, and these people are far more likely to develop AIDS or to die. This fact in itself very strongly suggests that HIV causes AIDS.89
HIV and AIDS in the United Kingdom, 1988-2002HIV and AIDS in the United Kingdom, 1988-2002
The benefits of more effective drug treatments can be seen in national statistics from rich countries in which most people have had access to them. On the right is a graph of HIV diagnoses, AIDS diagnoses and AIDS deaths in the UK between 1988 and 2002. This graph shows that the numbers of AIDS diagnoses and deaths fell by more than half between the end of 1995 and the end of 1998. This trend followed the widespread introduction of combination therapy.90
Similar patterns can be seen in statistics from other European countries, Canada, Australia and the USA.91 However, it should be noted that American statistics were distorted during the period 1990-1996 because of a major expansion in the AIDS surveillance case definition in 1993. For the first time, people could be diagnosed with AIDS on the basis of a low CD4+ cell count. The majority of these people would have gone on to develop AIDS-defining diseases before death, so would have been included in the statistics anyway, but the change in definition meant they were diagnosed earlier, and this skewed the statistics.
The distortion caused by the change in definition was temporary, and cannot account for the major declines in AIDS diagnoses and deaths that occurred in the USA during the late 1990s. Nor can the declines be explained by trends in HIV incidence.92 93 94 95 Incidence of AIDS-defining infections like PCP rose during the early 1990s and then decreased significantly between 1995 and 1998.96 97
The ability of antiretroviral drugs to prevent mother-to-child HIV transmission has been demonstrated around the world.98 Following the widespread introduction of these drugs during pregnancy, the number of reported AIDS cases among American children has fallen to around 100 per year, compared to nearly 1,000 per year in the early 1990s.99
Antiretroviral therapy, alongside treatment for opportunistic infections, is thought to have saved at least three million years of life in the USA alone.100
Drug abuse and other factors
Dissidents who claim that HIV does not cause AIDS have felt compelled to come up with alternative causes. These generally include recreational drugs (including heroin, cocaine, amphetamines and nitrite inhalants known as "poppers"), malnutrition, lack of clean drinking water, clotting factors used in blood transfusions, and anti-HIV drugs such as AZT. Some groups also suggest semen, "immune overload", antibiotics, benzene, stress, or lack of sleep.
In the early 1980s, when only a small number of AIDS cases had been reported, the medical establishment gave some of these possible causes very serious consideration. But such theories quickly lost favour as more cases emerged among men, women and children who did not fit the established risk groups, and it was established that affected people had been exposed to the bodily fluids of other affected people.101 Epidemiological data pointed to an infectious cause before HIV was ever isolated.102
Today, most scientists agree that controlled studies of drug users, heterosexuals, homosexuals, haemophiliacs and twin babies have consistently shown that HIV is the only factor that predicts who will develop AIDS. Associations in time and place between trends in drug use or promiscuity and trends in AIDS diagnoses are considered much too weak to prove causation.103 104
Dr Duesberg has claimed that some HIV-negative drug users have developed AIDS-like immune abnormalities and diseases. But his definition of "AIDS-like" is very vague, and none of these cases would merit an AIDS diagnosis.105 106 107
Antiretroviral drugs can have toxic side effects. However, there is no evidence that anti-HIV drugs cause the severe immune deficiency typical of AIDS, and there is abundant evidence that currently recommended courses of antiretroviral therapy can improve the length and quality of life of HIV-positive people.108 109 110 111
Certain AIDS-related diseases are more common among some population groups than among others. This is not surprising, and it does not mean that they cannot all have the same underlying cause.112 113
Severe malnutrition is a known cause of immune deficiency (though not the specific type of immune deficiency that is characteristic of AIDS). That is why all definitions of AIDS specify that there must be no evidence of severe malnutrition. Poor nutrition is also thought to make people with HIV more vulnerable to illness, so improving diet is an essential component of programmes to help HIV-infected people around the world. Still, such actions are not by themselves sufficient, because thousands of Africans who are well fed and cared for continue to die from AIDS. As the next section explains, there is no evidence that deterioration in diet or living standards can explain AIDS in Africa, which appears to be a totally new epidemic disease.
AIDS in Africa
Some dissidents claim there is no great new AIDS epidemic in Africa, just the same old diseases caused by poverty, hunger and poor sanitation. They say that official statistics are misleading because AIDS in Africa may be diagnosed on the basis of various clinical symptoms without an HIV test if none is available.114 We'll challenge these claims using four lines of argument.
Firstly, medical records from a number of African countries show marked increases in a number of AIDS-related diseases during the late 1970s and early 1980s. These records suggest that AIDS was probably rare or non-existent before that time.115
Secondly, as discussed above, numerous studies have found that people who test positive for HIV face a much higher risk of illness and death. Surveillance studies show that HIV prevalence rates have soared across sub-Saharan Africa since the early 1980s, and are now extremely high. It is therefore reasonable to estimate that millions are ill and dying.116
Thirdly, since the early 1980s, African countries with high HIV prevalence have suffered increased burdens of disease and death, as measured by censuses and surveys. For example:
* Between the 1980s and mid 1990s, adult death rates rose significantly in countries where HIV had been widespread for many years (such as Uganda, Zambia and Zimbabwe), but not in countries where rates had been lower.117 118
* Increases in death and disease have disproportionately affected young and middle-aged adults, especially those living in urban areas. Relatively well-paid professionals including teachers and doctors have been among the worst hit. This pattern is not typical of diseases caused by malnutrition or dirty water, which generally target the poor and the elderly.119 120 121
* In several countries, the number of orphans has risen so dramatically that communities can no longer cope, and child-headed households are now commonplace. Such changes indicate that sexually active adults are dying while children (and the elderly) are surviving. Household surveys have revealed a strong correlation between rates of orphanhood and adult HIV prevalence.122 123 124
* Patterns of disease have changed. For example, rates of Kaposi's sarcoma have soared,125 and tuberculosis - which was once confined to the poor, the weak and the elderly - today kills numerous well-fed Africans in the prime of life.126 127
Not all of sub-Saharan Africa has been equally affected by the recent changes. For example, Southern Africa has suffered much more than Western Africa, even though the regions have experienced similarly high levels of extreme poverty, malaria, food shortages and conflict. The only factor associated with the changes is HIV prevalence.128 129
Fourthly, the number of reported AIDS cases has risen across sub-Saharan Africa. Experts believe these statistics vastly underestimate the scale of the epidemics because the reporting systems are inadequate. This inadequacy is partly due to frequent misdiagnosis (compounded by AIDS-related stigma), but is mostly due to poor infrastructure and lack of access to healthcare. In addition, the quality of the reporting systems varies from one country to another. Nevertheless, it is possible to spot two clear patterns in the data.
The first obvious trend is that the number of reported AIDS cases increased everywhere during the 1980s. As in all other parts of the world, this increase followed a rise in HIV prevalence. The second trend concerns the number of AIDS cases reported per million of population. In general, the highest rates have been recorded by Southern African countries where HIV has been widespread for many years, while the lowest rates tend to come from Western African countries with historically much lower HIV prevalence. The lowest AIDS rate of all is reported by the island nation of Madagascar, where until recently HIV was extremely rare.130
The only major exception to the pattern in AIDS case rates is South Africa, which has reported relatively low figures. However, HIV prevalence did not reach very high levels in South Africa until the mid-1990s, several years later than in nearby countries such as Zambia and Zimbabwe. In addition, South Africa stopped reporting AIDS cases to the World Health Organisation in 1996, before most other African countries, and before the rise in HIV had had a chance to take effect.131
Compelling evidence of the impact of AIDS in South Africa since that time comes from studies of death certificates. These show that the annual number of reported deaths (from all causes) rose by 79% between 1997 and 2004. Among those aged 25-49 years old, the increase was 161%.132 Rates of death from AIDS-related conditions increased according to a distinctive age distribution, which peaked among the age groups 0-4 and 25-49 years. Other conditions showed no such pattern. The estimated number of AIDS deaths based on these data is similar to estimates based on HIV prevalence.133
What we don't know
There are still a few things we don't know about HIV and AIDS.
For example, we don't really know why both HIV and AIDS have become generally common in some African countries but not in Europe or the US – though we do have some theories. Contributing factors include the much higher prevalence of untreated sexually transmitted diseases in Africa (which greatly increase the chances of HIV transmission) and, quite possibly, differences between HIV subtypes.134 135 In addition, people who have poorer general health (including those who have malaria or tuberculosis) tend to have more HIV in their bodily fluids, which makes them more likely to transmit the virus.
Different patterns of sexual networking also have an effect. Viral loads are especially high during the first few weeks after infection, so the risk of transmission is then much higher. This means that people who have several concurrent sexual partners are able to spread the virus very efficiently before they test positive or fall ill. Studies suggest that, even though Africans do not report more sexual partners over a lifetime than other populations, concurrent partnerships are more common in Africa and most common in Southern Africa.136 137
Due to lack of access to HIV testing and treatment, as well as educational and cultural factors, the vast majority of Africans do not know their HIV status, and many people, especially women, find it very difficult to adopt strategies that would lower their risk of becoming infected or of infecting others. High levels of mobility, particularly of migrant workers, can also help to spread HIV.138
The concentration of an infectious disease among particular groups is not unusual. Hepatitis B is transmitted via much the same routes as HIV, and in Western countries it has similar risk groups. Hepatitis C (which is primarily spread via blood) is largely confined to injecting drug users, and recent increases in syphilis (usually sexually transmitted) have been fuelled by outbreaks among men who have sex with men. Surveillance statistics from throughout the Western world show that AIDS is becoming increasingly common outside the traditional risk groups, following a similar trend in HIV cases. In 2003, around a third of new American AIDS diagnoses, and two-thirds of those among women, occurred among non-drug using heterosexuals.139 Epidemiological evidence of male-to-female, male-to-male and female-to-male sexual transmission of HIV is abundant.140
Something else we don't fully understand is how HIV causes AIDS. Again, however, we do have some theories, which explain how the virus might be able to stop the immune system working properly in a number of ways, not just by directly killing cells.141 Ignorance about precisely how something happens is not proof that it does not happen.
Conclusion
There is no single scientific paper that proves HIV causes AIDS. Instead there are tens of thousands of papers containing a wide range of evidence that, taken together, make the case overwhelming.
People should be encouraged to question scientific orthodoxy. However, the views of AIDS dissidents, which have been well known for many years and thoroughly debated in scientific journals, have failed to win support. The core arguments of the Perth Group (that HIV has not been isolated according to their own particular rules) and Dr Duesberg (that no one fully understands how HIV causes AIDS) do not invalidate the wide range of evidence outlined on this page. The HIV theory is compelling because it provides a simple, unique cause that consistently accounts for all of the observed phenomena.
As an independent AIDS organisation, AVERT is primarily interested in what works. Studies have repeatedly shown that antibody testing is a highly effective way of predicting risk for AIDS; that modern antiretroviral treatment brings dramatic benefits; and that people who avoid exposure to HIV do not get AIDS. We will therefore continue wholeheartedly to recommend these things.
A cure for AIDS
There is no cure for AIDS. Although antiretroviral treatment can suppress HIV – the virus that causes AIDS – and can delay illness for many years, it cannot clear the virus completely. There is no confirmed case of a person getting rid of HIV infection. Sadly, this doesn’t stop countless quacks and con artists touting unproven, often dangerous “AIDS cures” to desperate people.
It is easy to see why an HIV positive person might want to believe in an AIDS cure. Access to antiretroviral treatment is scarce in much of the world. When someone has a life-threatening illness they may clutch at anything to stay alive. And even when antiretroviral treatment is available, it is far from an easy solution. Drugs must be taken every day for the rest of a person’s life, often causing unpleasant side effects. A one-off cure to eradicate the virus once and for all is much more appealing.
Distrust of Western medicine is not uncommon, especially in developing countries. The Internet abounds with rumours of the pharmaceutical industry or the U.S. government suppressing AIDS cures to protect the market for patented drugs. Many people would prefer a remedy that is “natural” or “traditional”.
Where’s the harm in fake AIDS cures?
Group of men looking at unproven AIDS cure
A man selling an unproven AIDS cure in Papua New Guinea
Unproven AIDS cures have been around since the syndrome emerged in the early 1980s. In most cases, they have only served to worsen suffering.
First of all, fake cures are a swindle. Someone who invests their savings in a worthless potion or an electrical zapper has less money to spend on real medicines and healthy food.
Many peddlers of bogus cures insist their clients avoid all other treatments, including antiretroviral medicines. By the time a patient realises the “cure” hasn’t worked, their prospects for successful antiretroviral treatment may well have diminished.
Fake cures may also cause direct harm to health. Inventors often refuse to reveal their recipes. Some so-called cures have been found to contain industrial solvents, disinfectants and other poisons. The dangers posed by the virgin cleansing myth – which advocates sex with children as a cure for AIDS – are only too clear.
Finally, the promotion of fake AIDS cures undermines HIV prevention. People who believe in a cure are less likely to fear becoming infected with HIV, and hence less likely to take precautions.
Why is it so difficult to cure AIDS?
Curing AIDS is generally taken to mean clearing the body of HIV, the virus that causes AIDS. The virus replicates (makes new copies of itself) by inserting its genetic code into human cells, particularly a type known as CD4 cells. Usually the infected cells produce numerous HIV particles and die soon afterwards. Antiretroviral drugs interfere with this replication process, which is why the drugs are so effective at reducing the amount of HIV in a person’s body to extremely low levels. During treatment, the concentration of HIV in the blood often falls so low that it cannot be detected by the standard test, known as a viral load test.
Unfortunately, not all infected cells behave the same way. Probably the most important problem is posed by “resting” CD4 cells. Once infected with HIV, these cells, instead of producing new copies of the virus, lie dormant for many years or even decades. Current therapies cannot remove HIV’s genetic material from these cells. Even if someone takes antiretroviral drugs for many years they will still have some HIV hiding in various parts of their body. Studies have found that if treatment is removed then HIV can re-establish itself by leaking out of these “viral reservoirs”.
A cure for AIDS must somehow remove every single one of the infected cells.
Reputable research on curing AIDS
Activating resting immune cells
Many researchers believe the best hope for eradicating HIV infection lies in combining antiretroviral treatment with drugs that flush HIV from its hiding places. The idea is to force resting CD4 cells to become active, whereupon they will start producing new HIV particles. The activated cells should soon die or be destroyed by the immune system, and the antiretroviral medication should mop up the released HIV.
Early attempts to employ this technique used interleukin-2 (also known as IL-2 or by the brand name Proleukin). This chemical messenger tells the body to create more CD4 cells and to activate resting cells. Researchers who gave interleukin-2 together with antiretroviral treatment discovered they could no longer find any infected resting CD4 cells. But interleukin-2 failed to clear all of the HIV; as soon as the patients stopped taking antiretroviral drugs the virus came back again.1 2
There is a problem with creating a massive number of active CD4 cells: despite the antiretroviral drugs, HIV may manage to infect a few of these cells and replicate, thus keeping the infection alive. Scientists are now investigating chemicals that don’t activate all resting CD4 cells, but only the tiny minority that are infected with HIV.
One such chemical is valproic acid, a drug already used to treat epilepsy and other conditions. In 2005 a group of researchers led by David Margolis caused a sensation when they reported that valproic acid, combined with antiretroviral treatment, had greatly reduced the number of HIV-infected resting CD4 cells in three of four patients. They concluded that:
“This finding, though not definitive, suggests that new approaches will allow the cure of HIV in the future.”3
Sadly, it seems such optimism was premature; more recent studies suggest that valproic acid has no long term benefits.4 5 In fact it’s quite possible that all related approaches are flawed because the virus has other hiding places besides resting CD4 cells. There is a lot about HIV that remains unknown.
Bone marrow transplants and gene therapy
In November 2008, a pair of German doctors made headlines by announcing they had cured a man of HIV infection by giving him a bone marrow transplant.6 The transplant - given as a treatment for leukemia - used cells from a donor with a rare genetic mutation known as Delta 32 that confers resistance to HIV infection. Twenty months after the procedure researchers reported they could find no trace of HIV in the recipient's bone marrow, blood and other organ tissues.
Other experts have said that more tests are required to verify this cure claim,7 though it is not the first of its kind. Of more than thirty HIV positive patients given bone marrow transplantation prior to 1996, two appeared to have been cured of their infection based on molecular testing and post-mortem biopsy samples.8 9
Even assuming it can be effective, bone marrow transplantation is too dangerous and costly for widespread use as a cure. Many patients die as a result of chemotherapy or reactions to the transplant, which is usually a last resort in treating life-threatening diseases. As Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, put it:
“It’s very nice, and it’s not even surprising. But it’s just off the table of practicality.”10
Nevertheless the German transplant does raise hope for related approaches. If scientists can find another way - such as gene therapy - to confer the same sort of protection against HIV as Delta 32 provides, then they may be able to stop the virus replicating. Research in this area is in its very early stages; it may be many years before a useful treatment is found, if at all.
Hope for the future
Some of the world’s top research institutions are today engaged in studies to learn more about the behaviour of HIV, resting CD4 cells and other hiding places. But the truth is that this field does not receive a lot of funding. Some people think the search for a cure is not worth much investment because the task may well be impossible.
Yet there are still those who remain hopeful, including the research charity amfAR, which in 2006 awarded nearly $1.5 million to AIDS cure researchers. Activist Martin Delaney is among those calling for an end to defeatism:
“Far too many people with HIV, as well as their doctors, have accepted the notion that a cure is not likely. No one can be certain that a cure will be found. No one can predict the future. But one thing is certain: if we allow pessimism about a cure to dominate our thinking, we surely won’t get one… We must restore our belief in a cure and make it one of the central demands of our activism.”11
How to spot fake AIDS cures and treatments
As already stated, there is no proven cure for AIDS. The best advice is to steer clear of anyone claiming otherwise. For those who find themselves tempted, here are a few pointers for spotting quack therapies.
Who makes the claims?
Try to find some information about the person or people promoting the product. What are their credentials? If someone claims to be a doctor then they should say what type of doctor, and where they got their qualifications.
What claims do they make?
Look at how the product is presented. Reputable scientists and doctors don’t use sensational terms such as “miracle breakthrough”. Also watch for evidence of poor scientific understanding; for example, no expert would refer to HIV as “the HIV virus” or “the AIDS virus”.
It is very rare for a medicine to be 100% effective for all patients. It is highly implausible that a single product could cure a wide range of unrelated diseases such as cancer, asthma, AIDS and diabetes. A real scientist would be extremely wary of making such claims.
What’s in the cure?
Many inventors won’t reveal what goes into their so-called cures. Ask yourself why this might be. Could it be that their methods wouldn’t stand up to scientific scrutiny?
It is important to remember that words like “natural” and “herbal” are no guarantee of safety. After all, hemlock and ricin (derived from castor beans) are both entirely natural and extremely toxic. As the U.S. Food and Drug Administration points out,
“Any product – synthetic or natural – potent enough to work like a drug is going to be potent enough to cause side effects.”12
What evidence do they offer?
To gain the approval of medical authorities, any new treatment must undergo very extensive testing. Countless products destroy HIV in the laboratory but are ineffective or dangerous when used by people. A proper trial involves a large group of volunteers divided randomly into two sets. One half uses the test product and the other receives a placebo (a harmless pretend medicine that looks like the real thing). During the trial, neither the scientists nor the volunteers should know who is getting which treatment. Afterwards, the results for the two groups are compared to see if the test product performed better than the placebo.
Virtually all promoters of “AIDS cures” cannot provide any data from large-scale, randomised human trials. Instead they rely on anecdotes, personal testimonies, laboratory experiments or small-scale trials with no placebo comparison. This type of evidence is always unreliable.
Personal testimonies are notoriously untrustworthy. Usually there is no way of knowing whether the people in question ever existed, let alone whether they were helped by the therapy. There have been cases of people being paid to pretend they’ve been cured. And even if a handful of people really did get better after they took the treatment, this doesn’t necessarily mean that it works; the improvements may just have been a coincidence. Many negative reports may have been left out of the promotional material.
Proving that HIV has been eradicated isn’t easy. Changes in symptoms or weight gain are not sufficient, and neither is a viral load test. Even if the test can’t detect HIV in the bloodstream (perhaps because the person has been on antiretroviral therapy), this doesn’t mean the virus has been cleared from all parts of the body. Much more thorough investigation is needed.
Beware of conspiracy theorists
Many sellers of fake medicines fall back on conspiracy theories to explain why their products haven’t undergone proper testing. They say that government agencies and the medical profession seek to suppress alternative treatments to safeguard the profits of the pharmaceutical industry.
This kind of allegation is a sure sign of a charlatan. In reality, leading scientists investigate all kinds of therapies that can’t be patented. For example, the U.S. government has funded research into using generic drugs (such as valproic acid) and human hormones (such as interleukin-2) as aids to ridding the body of HIV infection.
Do some research
Any important medical breakthrough will be reported in peer-reviewed journals such as Nature, Science or The Lancet. The mainstream media will pick up the story and leading experts will express their opinions.
Simply typing the name of a supposed cure into an Internet search engine and reading some of the resulting web pages will quickly establish whether it has widespread support. It is also worth searching an online medical database such as PubMed for scientific studies and reviews.
Consult an expert
Always talk to a doctor or other health professional before trying any medical treatment. If you need more information or a second opinion, try contacting a reputable health organisation or telephone helpline. Several American states have AIDS Fraud Task Forces dedicated to combating quackery, and local Food and Drug Administration offices can provide details of any action taken against a product or its manufacturer. Similar agencies operate in most other parts of the world.
Examples of false or unproven cures
What follows is a list of some products and methods that have attracted attention in recent years. It is safe to say that none of these is a cure for AIDS. Many of these so-called remedies are likely to do more harm than good.
President Jammeh’s AIDS cure
President Jammeh of The Gambia, a small country in West Africa, made a dramatic announcement in January 2007:
“I can treat asthma and HIV/AIDS and the cure is a day’s treatment. Within three days the person should be tested again and I can tell you that he/she will be negative... The mandate I have is that HIV/AIDS cases can be treated on Thursdays. That is the good news and the bad news is that I cannot treat more than ten patients every Thursday.”13
Three weeks later the president’s office released the results of viral load tests conducted on the first batch of patients. According to the official statement, “the herbal medicine and therapy administered by President Jammeh have yielded results beyond all reasonable doubts, that they are effective and can cure AIDS.”14 On closer inspection, however, the findings were far from convincing.
Of the four patients with HIV-1, one had a very high viral load, one high, one moderate, and one undetectable. Of the four patients with HIV-2, one had a low viral load and three had less than the detectable level.15
The fact that half of the patients still had detectable virus in their blood shows that the president’s cure cannot be 100% effective. More importantly, as already noted, an undetectable viral load does not prove that HIV has been eradicated. Some of the patients had previously been taking antiretroviral therapy, which often renders the virus undetectable. Apparently no evaluation was done before the president’s treatment began.
The viral load tests were conducted at a university in Dakar, Senegal, using samples of the patients’ blood. It has since emerged that the scientists who ran the tests were unaware of the samples’ origin. The Senegalese experts rebutted the president’s interpretation of their findings:
“There is no baseline ... you can’t prove that someone has been cured of AIDS from just one data point. It’s dishonest of the Gambian government to use our results in this way” Dr. Coumba Toure Kane16
“The interpretation by the Gambian authorities of the results of HIV antibody and viral load testing on blood samples sent to my laboratory is incorrect... Of those samples that were HIV-positive (66.66%), none could be described as cured.” Professor Souleymane Mboup17
The results of a second set of viral load tests, conducted by the National Institute of Hygiene in Morocco, were released in March 2007. For the first set of patients the numbers were similar to those found in Senegal. Among 31 other patients only six had undetectable viral loads.18
Clinical data for the third and fourth batch were released in October 2007. On this occasion the State House chose to withhold the name of the country in which the samples were tested. Twenty-seven of the seventy patients were found to have undetectable viral loads. Another twenty-seven had viral load counts above half a million, which is considered to be very high. The CD4 counts for twenty-seven of the seventy patients were below 200, which means they had progressed from HIV infection to AIDS. Curious repetitions within the viral load count data cast doubt on their accuracy.19
At least two of the president’s patients are known to have died.20
These unpromising outcomes have not shaken the president’s belief in his treatment, which is endorsed by the Gambian health ministry and is administered at state hospitals. President Jammeh, who has no medical qualifications, refuses to disclose exactly what goes into his cure. All he has revealed is that it involves seven herbs, “three of which are not from Gambia.”21 The treatment involves a green paste and a grey liquid each applied to the patient’s skin, and a yellowish tea-like drink. Even more important, according to President Jammeh, is the power of prayer:
“For everything that we do 90% we have to invoke the name of almighty Allah, and then 10% is what the herbs take care of.”22
Leading AIDS experts have expressed great concern about President Jammeh’s exploits. According to Dr. Pedro Cahn, President of the International AIDS Society:
“It is premature and unethical to label this product a cure if it has not been thoroughly tested and proven. Furthermore, to take patients off potent combination antiretroviral therapy, which has saved millions of lives since its introduction in 1996, is shocking and irresponsible.”23
A fifth batch of patients began treatment in February 2008.24 As of August 2008, the president was treating 122 people.25
Other herbal cures
Herbal mixtures comprise the most popular form of alternative AIDS therapy. Although it is possible that some of these treatments may benefit people with HIV, none is a proven cure.
* Comforter’s Healing Gift, a South African company, produces an extract of a plant called sonneblom (not sunflower). According to Freddie Isaacs, the inventor of the treatment and a co-director of the company, this product is a cure for AIDS.26 Other spokespersons have said such claims go against company policy, and the product should be described as a nutritional supplement until it has undergone proper testing. According to some reports one of South Africa’s leading attorneys, Christine Qunta, is closely connected with Comforter’s Healing Gift. South Africa’s opposition party has laid a charge against Qunta of authorising the sale of an unlicensed medicine.27
* Dr. Sebi (born Alfredo Bowman) says his “electric foods” can cure AIDS, cancer and many other illnesses. Sebi, who has offices in Honduras and the USA, has no medical qualifications and many of his views are totally at odds with basic principles of mainstream science. In Sebi’s opinion, AIDS (like all other diseases) occurs when “the mucous membrane has been compromised”.28 He says his plant extracts cure the illness by removing the mucous. Sebi was arrested in 1987 and again in 1997 for publishing false health claims and practising medicine without a licence.29 30 He has published no verifiable evidence to support his “AIDS cure”.
* IMOD was developed by scientists from Russia and Iran. When the Iranian government unveiled the drug in February 2007, many media sources, including Iran’s Fars News Agency, described IMOD as an “AIDS cure”.31 The official IMOD website makes no such claim, but does say that human trials of the drug found it increased CD4 counts in HIV positive people.32 No study reports have been published in medical journals. The research team did not respond to emails from the author of this article.
* Khomeini (or Khomein or Comein) was invented by Professor Sheik Allagholi Elahi of Iran, who set up a clinic in Uganda to sell this so-called AIDS cure for more than $1,500 per patient. The Ugandan Ministry of Health appointed a team of experts to monitor some of the few hundred people taking the treatment. After their study showed Elahi’s claims to be false, the government banned the use and distribution of Khomeini in April 2006, and Ehahi was arrested.33
* MAB Formula One and MAB Formula Two were developed by Ghanaian doctors and ethno-botanists led by Dr. Jacob Akumoah-Boateng. According to the researchers MAB Formula One kills HIV while MAB Formula Two boosts the immune system. Dr. Akumoah-Boateng says tests in the U.S. demonstrated the disappearance of HIV and HIV antibodies after the treatment was given, though none of the findings have been published in the medical literature.34
*
Ubhejane bottles on a shelf
The fake AIDS cure Ubhejane on sale in a South African pharmacy
Ubhejane, a brown liquid said to be made from 89 herbs, has been taken by many hundreds of HIV positive South Africans. Its creator, Zeblon Gwala, says Ubhejane reduces viral load and increases CD4 counts in HIV positive people. He advises that it should not be taken at the same time as antiretroviral treatment.
Ubhejane has often been referred to as a “cure for AIDS” and Gwala’s employees have reportedly promoted it as such, despite having no evidence from rigorous human trials.35 36 Scientists who have tested Ubhejane in the laboratory have stressed that they haven’t demonstrated any benefits to patients.37 South Africa’s opposition party has attempted to have Gwala prosecuted for fraud.38 In 2008, the Advertising Standards Authority of South Africa demanded the withdrawal of an advertisement stating that Ubhejane boosted immunity and reduced viral load, having found these claims to be unsubstantiated.39
Chemicals
Many people mistakenly believe that what destroys HIV in the test tube must also work in the human body. This is one reason why a number of disinfectants and other chemicals have been wrongly promoted as cures for AIDS.
* Armenicum (also known as iodine-lithium-alpha-dextrin or ILalphaD) is a type of iodophor, a chemical that slowly releases iodine when mixed with water. According to Armenian scientists Armenicum, injected into the bloodstream, acts as an antiretroviral drug by blocking the replication of HIV. They claim to have evidence that the substance reduces viral load and increases CD4 counts in HIV positive people. The inventor of Armenicum, Alexander Ilyen, once said he was convinced it would lead to an AIDS cure.40 No studies of HIV positive people treated with Armenicum have been published in peer-reviewed journals. In a report on an animal experiment published in June 2007 the Armenicum research team admits that, “The systemic therapeutic application of iodophores has not yet been accepted”.41 A BBC investigation of Armenicum in 1999 found that the health of two American men got worse after they took the drug.42 Nevertheless the Armenian government has invested most of its HIV treatment resources in Armenicum, which costs more than three times as much as antiretroviral therapy. By late 2008, ten years after the drug was introduced, around 800 people had taken Armenicum.43
* Colloidal silver is a suspension of extremely tiny silver particles in water. Many websites say this clear, colourless liquid effectively treats a wide range of bacterial and viral infections, including HIV infection. While it is true that colloidal silver kills germs in laboratory conditions, there is no reliable evidence of any benefit in people. Contrary to the claims of many retailers, colloidal silver is not harmless. Regular use can cause an irreversible bluish-grey discolouration of the skin, known as argyria.44 Consuming very large amounts of colloidal silver may lead to neurologic problems, kidney damage, stomach distress, headaches, fatigue, and skin irritation.45 There has been at least one reported case of a man falling into a coma after ingesting colloidal silver.46 In America it is illegal for retailers to make any health claims for this product.47
* Tetrasil (or Imusil) is a substance containing tetrasilver tetroxide. A patent held by Dr. Marvin S. Antelman claims that this simple chemical compound cures AIDS by “electrocuting” HIV.48 Dr. Antelman admits his approach to AIDS is “non-conventional” and he does not trust viral load tests: “Accordingly we have patients who display viral load reduction and those that do not who are nevertheless cured of AIDS”, he has said.49 Tetrasilver tetroxide is more commonly used for disinfecting swimming pools.50 After it was promoted as an AIDS cure in Zambia the government banned Tetrasil because it has no proven benefits for people living with HIV.51 In America it is illegal to promote Tetrasil for the treatment or prevention of any disease.52
* Virodene is based on the industrial solvent dimethylformamide (DMF). In the late 1990s this chemical was touted as a possible cure for AIDS. For several years senior members of the South African government, including Thabo Mbeki, vehemently supported research into Virodene as an AIDS treatment, against the advice of medical experts. South Africa’s drug regulators have long prohibited use of Virodene as it has no proven benefits. Laboratory studies have found that DMF does not destroy HIV or inhibit its replication. The only trial of its effectiveness in humans, conducted in Tanzania, found that Virodene did not reduce viral load and had only marginal effects on the immune system.53 DMF is considered a toxic substance; workers are advised to avoid skin contact with the chemical because it may cause serious liver damage.54 55 Imunoxx, which a Namibian company markets as an immune booster, is essentially identical to Virodene.
Oxygen therapy
* Hydrogen peroxide, diluted in water, is commonly used as a bleach and a disinfectant. Some alternative health practitioners advocate drinking, injecting or bathing in weak solutions of this chemical as a cure for AIDS, flu, cancer and other illnesses. There is no evidence to support these claims. Several people have died as a result of swallowing or injecting hydrogen peroxide.56 57
* Ozone is an unstable form of oxygen gas. Ozone therapy has been proposed as a treatment or cure for many illnesses, including HIV infection. One delivery method is autohemotherapy, which involves removing some of a patient’s blood, exposing it to ozone, and then putting it back into the patient. Alternatives include pumping the gas into the rectum, drinking water containing ozone bubbles (ozonized water, which contains hydrogen peroxide), or injecting the gas into the bloodstream. Studies of ozone autohemotherapy in HIV positive people have found it has no significant effect on CD4 counts and other outcomes.58 59 According to the U.S. Food and Drug Administration, “Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in a concentration far greater than that which can be safely tolerated by man and animals.”60 It is illegal for retailers in America to make any health claims for ozone generators.
Electrical zappers
* Dr. Hulda Clark (who is not a licensed medical doctor) promotes a range of products said to cure AIDS including an electrical “zapper” which, by generating low voltage electricity, is supposed to kill parasites, bacteria and viruses in the body. No proper studies of the zapper have been conducted. Dr. Clark’s methods of diagnosing HIV are highly unconventional; she believes that HIV comes from intestinal worms in the presence of benzene, and that HIV can be found in snails.61 It is therefore doubtful whether the people she claims to have cured of HIV infection were ever really infected.62 Dr. Clark left America after being taken to court for practising medicine without a licence.63 She now runs a clinic in Tijuana, Mexico, where she has also run into trouble with the authorities.64
* The Bob Beck Protocol involves a set of therapies devised by the late Dr. Bob Beck (who was not a medical doctor) that are supposed to cure AIDS, cancer and all other diseases. The four components are electric currents, magnetic pulses, colloidal silver and ozonized water. There is no good evidence that electricity can cure any infection. Claims about the healing powers of Bob Beck’s devices are based entirely on test tube studies and unverifiable anecdotes.
Immune boosters
Some so-called AIDS cures are meant to stimulate the human immune system. Since HIV makes new copies of itself by infecting active immune cells, there is a real danger that such therapies will hasten the spread of the virus rather than contain it.
* Dr. Gary R. Davis got his idea for an AIDS cure from a goat that appeared in his dreams. The late Dr. Davis never prescribed his goat serum treatment (known as BB7075) to HIV positive Americans due to legal restrictions. In 1998 one young girl, Precious Thomas, was given the serum by her mother, who stole it from Davis’ office. Some websites say the girl was cured of HIV infection, based on a viral load test conducted soon afterwards.65 In a 2006 interview, however, Precious Thomas made clear that she was still infected with HIV.66 After being denied approval in America, Dr. Davis and his associates tried to conduct goat serum trials in Ghana. Again he was stopped because “the supporting evidence for asking for registration and use of the serum was totally inadequate”.67 In late 2006, a few months before Dr. Davis’ death, the BBC exposed an attempt by a British company to test the substance on dozens of people in Swaziland, despite the lack of toxicity tests and other necessary preliminary studies.68
* The Antidote – a drug derived from a crocodile protein – has been promoted via spam email and websites with the promise that “It kills all known deadly viruses and bacteria in the body”.69 Absolutely no scientific evidence has been offered to support this claim.
* V-1 Immunitor (or V-AIM or Immureboost) is a pink pill containing antigens taken from the pooled blood of HIV positive people. A clinic in Thailand began distributing V-1 in 2001. Demand soared when the pill’s inventor, Vichai Jirathitikal, said it had eliminated HIV in two patients.70 The Thai Ministry of Public Health responded by conducting a study of those receiving V-1; the findings were not encouraging. According to a government minister, “the pill does not have any effect on the body’s immune system, white blood cell count and amount of the virus in the blood”.71 Other studies of the so-called vaccine – all carried out by employees of its manufacturer – do not provide convincing evidence of benefit. AIDS patients treated with V-1 typically survive for a matter of weeks, as opposed to the years achieved through antiretroviral treatment.72 Although the company has said that people treated with V-1 have “serodeconverted” from HIV-positive to HIV-negative,73 this claim is based on unreliable evidence and is not taken seriously by the scientific community.74 The manufacturing and sales licences for V-1 in Thailand were revoked in April 2003.75 76 Apparently undaunted, Vichai Jirathitikal and a company called Immureboost have continued to promote the product under the new name V-AIM, describing it as a therapeutic vaccine rather than a cure for AIDS.77
Faith-based cures
Religious bodies have done much to help the response to AIDS, especially by caring for the sick. Sadly a small minority of religious leaders have abused the trust placed in them by promising to cure AIDS through faith, sometimes in exchange for money or gifts. Most reports come from sub-Saharan Africa, where evangelical Americans are among those implicated.78
One of the most startling examples of recent times concerns an Ethiopian church where thousands of HIV positive people have sought a cure in showers of holy water. At one time, pilgrims were told to trust in faith alone and to refuse medication.79 Church patriarch Abune Paulos has since endorsed the use of antiretroviral treatment:
“What we are saying is taking the drugs is neither a sin nor a crime. Both the Holy Water and the medicine are gifts of God. They neither contradict nor resist each other.”80
The virgin cleansing myth
The myth that sex with a virgin can cure sexually transmitted diseases has a long history in Europe and elsewhere. Since the emergence of the AIDS epidemic, there has been much concern that this belief might encourage the rape of children, especially in Africa where HIV is widespread. A number of horrific reports in the popular press have fuelled such anxiety.
road sign
A road sign in Zambia confronting the "virgin AIDS cure myth"
Belief in the virgin cleansing myth has been reported from Africa, Asia, Europe and the Americas. There is no doubt that it has led to abuse of not only children but also the disabled (who are often assumed to be virgins).81 Nevertheless, the scale of the myth’s impact is disputed because it is not the only motivation behind child rape.82 83 In many cases the goal is more likely to be prevention than cure: men are seeking partners who are less likely to have HIV.
Thankfully efforts are being made to dispel the virgin cleansing myth around the world. But to effectively clamp down on child rape, such campaigns must be accompanied by changes to the cultural and legal environment that enables abuse to take place.
Spontaneous cures: Andrew Stimpson
Occasionally there are reports of HIV seeming to vanish for no obvious reason. One especially sensational story broke on 13th November 2005, when two British newspapers reported that a 25-year old Scot, Andrew Stimpson, had become the first person to be cured of HIV infection.84 85
In interviews with the two papers, Stimpson said he first suspected he might have HIV in 2002, after several weeks of feeling tired and feverish. Knowing his partner had been HIV positive for a number of years, Stimpson visited the Victoria Sexual Health Clinic in London for an HIV antibody test in May. The result was negative, but he was encouraged to return for further tests, as HIV antibodies often do not appear in the blood until several weeks or even months after initial infection.
In August 2002, Stimpson returned for three more HIV antibody tests. His first, taken on the 15th, was “indeterminate” (i.e. neither definitely positive nor negative), but the following two (taken on 20th and 23rd August) both found him to be HIV antibody positive. However, a viral load test showed the amount of virus in his blood was low, so he was not prescribed antiretroviral therapy. He made a personal choice to start taking multivitamin and mineral tablets and other dietary supplements.
For fourteen months Stimpson remained surprisingly healthy, so much so that, in October 2003, his doctor offered him a repeat test for HIV antibodies. Remarkably, the test came back negative. Two more, carried out in December 2003 and March 2004, also gave negative results.
Andrew Stimpson tried to launch a legal case against the Chelsea and Westminster NHS Trust (CWT) which had tested him, assuming his results had been mixed up with those of another client. The blood samples associated with his original positive diagnosis and his subsequent negative results were retested, and the DNA from the samples compared to his. All the samples were found to belong to Stimpson, and retesting produced the same “positive then negative” antibody results. According to Stimpson:
“After the repeat tests my doctor came into the room saying, ‘You’ve cured yourself! This is unbelievable.’”86
Andrew Stimpson’s story became an overnight media sensation. But a statement from the CWT cast doubt on the cure claims:
“It is probable that there was never any evidence of Mr Stimpson having the HIV virus but rather that there was transient evidence of an antibody response to the virus present in his bloodstream when he had the initial tests... The antibody testing is exquisitely sensitive and the smallest measure can be recorded which is probably what happened in this case.”87
A spokesperson for the CWT later said they had not categorically stated that Andrew Stimpson’s case was an example of a false positive test result, but that it was one of a number of scenarios that needed to be considered.88 The media quickly accepted the “false positive” explanation, and by the end of the month the story had ceased to be of interest to them.
The only news since then dates from June 2006, when the Guardian newspaper reported that Stimpson was still working with doctors, but that because of medical confidentiality, very little more was known about the case. However, Anna Maria Geretti, a clinical virologist at the Royal Free Hospital, was willing to speculate:
“These follow-up tests are very complicated. They could take over six months. But personally, I’m sceptical that they will find a cure from this case.”89
The most likely explanation remains the occurrence of a highly unusual false positive antibody test result. This may happen if the test detects a non-HIV antibody (i.e. a similar antibody produced against a different virus) or, theoretically, because there are somehow HIV antibodies present without an actual HIV infection. Occasionally a false positive may be the result of a faulty test, though a second backup test would normally eliminate this possibility.
Although receiving three false positive results would be exceedingly unusual, some scientists believe it is more plausible than a spontaneous cure. In any case it’s extremely unlikely that, as some newspapers suggested, the multivitamins and dietary supplements that Andrew Stimpson took would have had any effect on his “seroreversion” (the process of going from HIV antibody positive to HIV antibody negative). Millions of people living with HIV take multivitamins and minerals; while such supplements may help to maintain good general health, there is no evidence that they can eliminate HIV infection.
AIDS vaccine
An AIDS vaccine does not yet exist, but the idea is undergoing research and development.
Why do we need an AIDS vaccine?
Even a partially effective AIDS vaccine could save millions of lives. Experts have calculated that a vaccine that is 50% effective, given to just 30% of the population could reduce the number of HIV infections in the developing world by more than half over 15 years. More effective AIDS vaccines could cut the infection rate by more than 80%.1
Efforts to develop a vaccine against HIV and AIDS have been underway for many years. In 1996, Dr Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases said:
“Developing a safe and effective vaccine against HIV is critical to our efforts to control the devastating pandemic of HIV and AIDS” 2
This statement is still true today.
So what is a vaccine?
A vaccine is something that teaches the body to recognise and defend itself against viruses or bacteria that cause disease. Vaccines either help to prevent infection, or help to prevent or delay illness in people who are already infected. A vaccine is not the same thing as a cure for AIDS.
Effective vaccines have already been developed for some diseases, such as smallpox, polio and tetanus, and these have saved millions of lives. But there is still no vaccine against HIV, the virus that causes AIDS.
What would be the advantage of an AIDS vaccine?
An AIDS vaccine would have a number of key advantages over today’s HIV prevention options. In particular, the protection offered by a vaccine during sex would not depend on the consent of both partners (unlike condom use), and would not require behaviour change (unlike abstinence). A vaccine would also be invaluable for couples wishing to conceive a child while minimising the risk of HIV transmission.
Children could be given a vaccine before ever being exposed to the virus, and ideally this would protect them from all routes of HIV transmission. Vaccinating large numbers of people would probably require relatively little equipment and expertise, and would be much simpler and cheaper than providing antiretroviral treatment for those already infected.
How might an AIDS vaccine work?
an antibody in contact with an HIV protein
This image shows an antibody (green) in contact with an HIV protein (yellow & red), which is a possible target for AIDS vaccine developers.
An AIDS vaccine could be effective in either of two ways. A “preventive” vaccine would stop HIV infection occurring altogether, whereas a “therapeutic” vaccine would not stop infection, but would prevent or delay illness in people who do become infected, and might also reduce the risk of them transmitting the virus to other people. Although a preventive vaccine would be ideal, a therapeutic vaccine would also be highly beneficial.
The basic idea behind all AIDS vaccines is to encourage the human immune system to fight HIV. The immune system works using a combination of cells and chemicals called antibodies. Early vaccine research focused on teaching the immune system to produce antibodies that would block HIV entering human cells. However, products designed to work this way failed in clinical trials because the antibodies worked only against lab-cultured HIV, not against the wild strains of the virus.
Recent research has focused on encouraging the immune system to produce cells to fight HIV. Nevertheless, many scientists believe such “cell-mediated” approaches will not be very effective on their own, even as therapeutic vaccines. It seems likely that a really effective vaccine will have to take a two-pronged approach involving both cells and antibodies.
Why is it difficult to develop an AIDS vaccine?
Developing an AIDS vaccine is a very difficult challenge for scientists. There are many reasons for this, including:
* Nobody has ever recovered from HIV infection, so there is no natural mechanism to imitate
* HIV destroys the immune system cells that are meant to fight against it
* Soon after infection, HIV inserts its genetic material into human cells, where it remains hidden from the immune system
* HIV occurs in several subtypes, each of which is very different from the others
* Even within each subtype, HIV is highly variable and constantly changing
* There are no good animal models to use in experiments
Can these difficulties be overcome?
There are reasons to be optimistic about the search for an AIDS vaccine, despite the slow progress so far. Vaccines against other diseases took many decades to develop, whereas HIV was only discovered in the mid 1980s. It is therefore much too early to give up hope, especially given the current speed of scientific progress. In the past, some experts doubted the possibility of an effective polio vaccine, yet today polio is close to being eradicated thanks to successful vaccination programmes.
One particular reason for remaining hopeful is that most people remain healthy for several years after becoming infected with HIV, and a small minority have survived as long as 20 years without developing AIDS, even though they never entirely rid themselves of the virus. Also it appears that a few people have some kind of natural resistance to HIV infection, meaning they never become infected despite repeated exposure to the virus. These facts suggest that the immune system can be quite effective at controlling HIV.
Who is supporting research and development?
In 2008, the public, philanthropic and private sectors invested around $868 million in preventive AIDS vaccine research and development.3 The public sector provided around 84 percent, the philanthropic sector accounted for 12 percent, and the commercial sector accounted for the remaining 4 percent. Although funding for vaccine research has increased substantially since 2000, the 2008 contributions were a 10 percent decrease from 2007.4
The quest for an AIDS vaccine is aided by the not-for-profit International AIDS Vaccine Initiative (IAVI), which helps to support and coordinate vaccine research, development, policy and advocacy around the world. In addition an alliance of organisations called the Global HIV/AIDS Vaccine Enterprise exists to coordinate research and promote scientific cooperation and collaboration.
How are the possible AIDS vaccines tested?
Any potential AIDS vaccine must pass through three phases of clinical trials before being judged safe and effective. The first phase usually lasts from twelve to eighteen months, whereas the last phase can take three or four years to complete. In most cases volunteers taking part in the trial must be HIV-negative at the start of the trial, though it is important also to test safety in those who are already infected. Some therapeutic vaccine candidates may be tested on HIV-positive people to see if they can delay disease progression.
* Phase I involves a small number of volunteers to test the safety of various doses
* Phase II involves hundreds of volunteers to further assess safety and, in some cases, positive responses
* Phase III involves thousands of volunteers to test safety and effectiveness
A recent innovation is the Phase IIb trial, a larger form of the Phase II trial that provides some indication of effectiveness.
Trials of AIDS vaccines are made more difficult by the ethical obligation to provide condoms and prevention counselling to all those who take part. Providing such services lowers the overall rate of HIV transmission, which increases the number of volunteers required to produce a significant result.
What vaccine trials have already taken place?
AIDSVAX
The first AIDS vaccine candidate to undergo Phase III trials was called AIDSVAX. Two separate studies were conducted. One had around 5,400 participants - mostly gay American men - while the other involved around 2,500 injecting drug users in Thailand. The vaccine was made from a single HIV protein and was meant to stimulate a protective antibody response. The trials began in 1998 and 1999 respectively, and ended in 2003. No beneficial effect was found in either population group.5
STEP and Phambili
Two Phase IIb trials of a vaccine candidate created by the pharmaceutical company Merck were halted in September 2007. The studies - known as STEP and Phambili - had been expected to produce their first results by 2010. They were stopped when researchers found people receiving the vaccine were no less likely to become infected with HIV than those given the placebo - the version that had no medicinal properties. The STEP trial had started in 2004 in the USA, Canada, Australia, Peru and the Caribbean; the Phambili trial had begun in January 2007 in South Africa.6 7
There is some concern that slightly more HIV infections occurred among people who received the Merck vaccine than among those who took a placebo. The vaccine was delivered using adenovirus type 5, which causes the common cold. It has been suggested that the vaccine may have provoked a different immune response among people who already had some immunity to the adenovirus strain, and that this may have made them more susceptible to HIV infection. This hypothesis - which is supported by laboratory evidence8 - raises questions about the use of adenovirus in future vaccines.9 It has also been noticed that uncircumcised men were four times more likely to become infected with HIV if they received the vaccine than if they received the placebo.10
Following the failure of the trial several other trials were delayed to ensure the design of the trail took into account what had been learnt from the Merck vaccine study.
Leading vaccine researcher Dr. Gary Nabel described the results of the Merck vaccine trial as “a big blow to the field”.11 Nevertheless, Dr. Seth Berkley, President and CEO of the International AIDS Vaccine Initiative, has stressed that the outcomes are not all negative:
“Though the Merck candidate failed, the trial did not. The contribution of the volunteers was not in vain. As a result of their dedication, the field will have new data that will inform future vaccine design, help with the prioritization of candidates in the pipeline and guide decisions on how to best proceed with ongoing and upcoming trials.”12
ALVAC / AIDSVAX trial
In 2006 AIDSVAX was used in another Phase III trial in combination with ALVAC.13 It was hoped that a trial combining AIDSVAX, which promotes the production of antibodies to HIV, and ALVAC, which is designed to stimulate a cellular response to the virus, would prove more effective than the previous AIDSVAX trial.14 The trial recruited 16,402 young adults in Thailand.
The results, published in late 2009, showed that 74 trial candidates who received a placebo became infected with HIV, compared to 51 who had received the vaccine candidate.15 Although further examination produced mixed results, the analysis which the authors claimed was most relevant showed the vaccine prevented HIV infection by 31.2%. Drawing on this statistically significant result, the authors concluded that the trial showed a "modest protective effect of vaccine".16
Opinion differed over the significance of the study. Seth Berkley, of the International AIDS Vaccine Initiative was optimistic:
“The outcome is very exciting news and a significant scientific achievement. It’s the first demonstration that a candidate AIDS vaccine provides benefit in humans. Until now, we’ve had evidence of feasibility for an AIDS vaccine in animal models. Now, we’ve got a vaccine candidate that appears to show a protective effect in humans, albeit partially.” - 17
However, Dr. Otto Yang, an immunologist at University of California, LA, said:
"the results are weak enough that we need to be very careful about assigning too much optimism to them... It seems not so likely that the vaccine really did what it was intended to do". - 18
What vaccine trials are now underway?
By 2009, twenty-nine human trials of preventive HIV/AIDS vaccines were taking place worldwide.19 This number included one Phase II trial; three Phase I/II trials and twenty-five Phase I trials.
How soon could we have an effective vaccine?
“The path forward is not clear. I think there is agreement on that. Anybody who talks about a timeline for a vaccine is being silly and uninformed.”
- Professor John Mellors
In 1984, at the press conference arranged to announce the discovery of HIV, the US Health and Human Services Secretary Margaret Heckler said she hoped a vaccine against AIDS would be ready for testing in about two years.20
Unfortunately, the problem has turned out to be much more challenging than Secretary Heckler expected. Today’s researchers agree that the quest for an AIDS vaccine still has a long way to go. It is possible that the search could last decades.
“HIV infection has never provided scientists with a proof of concept of predictable protection, which historically has been the guiding principle for successful vaccine development.” – Dr Anthony S. Fauci, Director of NIAID21
The failure of the STEP trial in 2007 in particular has led some scientists to question whether the current approach to AIDS vaccine development has much chance of success, given that it favours products that work in a similar way to the failed Merck candidate.
“The path forward is not clear. I think there is agreement on that. Anybody who talks about a timeline for a vaccine is being silly and uninformed. It will require an incremental process of knowledge, and experimentation, and testing of ideas.” - Professor John Mellors22
The news media regularly announce a new “breakthrough” in AIDS vaccine research. However, most of these stories refer to products in Phase I or Phase II trials, where there has been no evidence of the product actually working in humans. Such stories are realistically talking only about potential breakthroughs.
Few if any vaccines are 100% effective. Most probably the first AIDS vaccines to succeed in trials will offer only partial protection, and these may need to be improved or combined with other products before being suitable for widespread use. Vaccine development is likely to proceed by small, incremental steps; we are unlikely to see an immediate “miracle breakthrough”.
Reaching people in need
If trials conclusively find a particular vaccine to be safe and effective then the next challenge is to distribute it and help people access it. In addition both governments and individuals will need to be convinced that the product is worth investing in. The process of getting a vaccine to all the hundreds of millions of people in need could take many years.
An important consideration is whether a vaccine could undermine the popularity of existing HIV prevention methods, such as condoms. If a product is only partially effective (as is almost inevitable) then experts will have to weigh up the potential risks and benefits very carefully before considering distribution. Upon release of any product, awareness-raising and prevention efforts will need to be redoubled to counter the risk of complacency.
Conclusion
It is very unlikely that HIV and AIDS will ever be eradicated without new scientific developments. Eventually, unless great progress is made in prevention, the number of people living with HIV will outstrip the resources available for treatment. The search for an effective vaccine must therefore be one of the very highest priorities for scientific research.
However, it is not realistic to expect such research to produce a major breakthrough for some time yet, and we should be wary of news stories suggesting otherwise. Any new discovery needs to undergo trials lasting years, and must then be distributed around the world before we will see its full benefits.
There is also a danger that focus will be diverted from existing successful initiatives that require continued funding, such as prevention and antiretroviral treatment programmes.
“The world is jumping into a flurry of excitement about a possible solution many years down the line – nobody seems to be in a similar flurry about the fact that, right now, two out of three people who need ART to stay alive aren’t receiving it.” – Paula Akugizibwe, AIDS and Rights Alliance for Southern Africa23
Millions of lives can be saved using the knowledge and tools already at our disposal, provided the world commits itself wholeheartedly to the cause.
Microbicides
A microbicide for HIV does not yet exist, but the idea is currently being researched and developed.
What is a microbicide?
A microbicide is something designed to destroy microbes (bacteria and viruses) or to reduce their ability to establish an infection. A microbicide for preventing HIV infection would be applied to the vagina or rectum to prevent the virus being passed on during sex.
What are the advantages of HIV microbicides?
A microbicide would share many of the advantages of an AIDS vaccine. It would be especially useful for women unable to insist on their partner using condoms, who might be able to use a microbicide without their partners knowing. However, a microbicide would not be able to prevent all forms of HIV transmission, and would require regular reapplication. Unlike vaccines, an effective microbicide must be made into a commodity that people will want to use regularly, such as a cream, gel or vaginal ring.
How might an HIV microbicide work?
A microbicide could work in at least four different ways:
* Kill or inactivate HIV
* Stop the virus entering human cells
* Enhance the body’s normal defence mechanisms against HIV
* Inhibit HIV replication
It is possible that a microbicide could work in much the same way as a vaccine, so research in one area could benefit the other. Alternatively, a microbicide could work in a similar way to today’s antiretroviral drugs, or it could act like a detergent by disrupting the outer coating of the virus.
What are the challenges in developing HIV microbicides?
There are many chemicals that kill HIV, including undiluted household bleach. But what is needed for a microbicide is something that works against HIV without causing discomfort or irritation. For example, when researchers investigated using the spermicide Nonoxynol-9 as an HIV microbicide they were surprised to find it actually increased the rate of transmission, probably because it caused vaginal lesions and inflammation, which made it easier for HIV to establish an infection, even though Nonoxynol-9 killed the virus in lab tests.1
For a microbicide to become popular, researchers must develop not only the active ingredient but also a microbicide that is socially acceptable, affordable and easy to apply. Ideally it would provide protection for several days or even weeks at a time.
Another major issue is how a microbicide affects sperm. To reach all those in need, scientists will have to develop both contraceptive and non-contraceptive microbicides.
Who is supporting research and development?
In 2008 around $244 million was invested in microbicide research and development - up by 8% on the previous year. About 85% of this money came from the public sector, 14% came from the philanthropic sector and 1% was accounted for by commercial companies (only $2.5 million).2
At present no major pharmaceutical firm is investing significant amounts of its own money in microbicide research because it is complex and the market is uncertain.3 As Professor Jonathon Weber has stated:
"[Microbicides] are perceived as drugs for Africa, and no one makes money from Africa" - 4
How are the possible microbicides tested?
There are three phases of clinical trials that a potential mircobicide must pass through before it is judged effective and safe. Phase I tends to last between twelve and eighteen months, whereas the final phase can take up to three or four years.
* Phase I involves a small number of volunteers to test the safety of various doses
* Phase II involves hundreds of volunteers to further assess safety and, in some cases, positive responses
* Phase III involves thousands of volunteers to test safety and effectiveness
The Phase IIb trial, a recent innovation, is a larger variant of the Phase II trial.
All microbicide trials provide condoms and prevention counselling to all participants, as an ethical obligation. As a result, the overall rate of HIV transmission is lowered, which means more volunteers are needed to produce a significant result. Most volunteers must be HIV-negative at the beginning of the trial, though it is also important to test safety in those who are already infected.
How many microbicides trials are under way?
By 2009, ten HIV microbicide candidates were undergoing trials.5 This included Phase III trials of PRO 2000 and Buffergel and a Phase IIb trial of Tenofovir gel.
* PRO 2000 is a type of entry inhibitor
* Buffergel maintains acidity in the vagina
* Tenofovir gel is based on an antiretroviral drug
There are more than 60 organisations involved in the development of microbicides. This includes sponsors, funders and research groups.6
Which microbicide trials have recently ended?
In August 2006, Family Health International decided to halt a Phase III trial of a surfactant called SAVVY after preliminary results showed no evidence of a protective effect. The organisation has no plans to further investigate this product.7
A computer-generated image of HIV exiting a cell
A computer-generated image of HIV exiting a cell
Two Phase III trials of an entry inhibitor called cellulose sulphate (also known as Ushercell) were halted in January 2007 after some sites recorded a higher HIV infection rate among women who used the gel, compared to those who were given a version that had no medicinal properties (a placebo). This result led to speculation that the gel may have increased the risk of HIV transmission. Later analysis indicated that the higher infection rate may have been due to chance.8
In February 2008, researchers announced the results of a Phase III trial of Carraguard, an entry inhibitor based on carrageenan, which is derived from seaweed. The product - the first ever to complete Phase III testing - was shown to be safe, but had no significant effect on HIV transmission.9
Also in February 2008, it was decided that the largest PRO 2000 trial should stop testing a higher strength version of the product because it was unlikely to be beneficial. A weaker version was investigated, but in 2009 the results did not reach a level of statistical significance.10 11 Results from a much larger study of PRO 2000, sponsored by the Medical Research Council and the Department for International Development in the United Kingdom, are expected in late 2009.
Conclusion
If one of the microbicide candidates were successful in preventing HIV infection, it would be a while before it would become widely available. Any successful product would have to undergo review and licensing by regulatory agencies before becoming available to the public. It would take time to work out the best formulation and dosage; find a suitable delivery method; and distribute the product. Also, if an effective product is produced it may be difficult finding investors, as the microbicide will have to be available to women in low- and middle- income countries and therefore profit margins will be low.12 In addition, any successful microbicide will only be partially protective and so would have to be complemented with other prevention methods.13
Whilst it is important to ensure continued funding and support for microbicide development, it would not be helpful to be overly optimistic about the effectiveness and potential availability of such a product. A microbicide will not be a ‘silver bullet’ for ending the epidemic, but rather another tool to add to existing prevention efforts.
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