Origin of HIV

Debate around the origin of AIDS has sparked considerable interest and controversy since the beginning of the epidemic. However, in trying to identify where AIDS originated, there is a danger that people may try and use the debate to attribute blame for the disease to particular groups of individuals or certain lifestyles. The first cases of AIDS occurred in the USA in 1981, but they provide little information about the source of the disease. There is now clear evidence that the disease AIDS is caused by the virus HIV. So to find the source of AIDS we need to look for the origin of HIV. The issue of the origin of HIV could go beyond one of purely academic interest, as an understanding of where the virus originated and how it evolved could be crucial in developing a vaccine against HIV and more effective treatments in the future. Also, knowledge of how the AIDS epidemic emerged could be important in both mapping the future course of the epidemic and developing effective education and prevention programme as well as proper counseling and safer sex.

What type of virus is HIV?

HIV is part of a family or group of viruses called lentiviruses. Lentiviruses other than HIV have been found in a wide range of non human primates. These other lentiviruses are known collectively as simian (monkey) viruses (SIV) where a subscript is used to denote their species of origin.

So where did HIV come from?

Did HIV come from an SIV?

It is now generally accepted that HIV is a descendant of simian (monkey) immunodeficiency virus (SIV). Certain simian immunodeficiency viruses bear a very close resemblance to HIV-1 and HIV-2, the two types of HIV.

For example, HIV-2 corresponds to a simian immunodeficiency virus found in the sooty mangabey monkey (SIVcpz), sometimes known as the green monkey, which is indigenous to western Africa.

The more virulent strain of HIV, namely HIV-1, was until very recently more difficult to place. Until 1999 the closest counterpart that had been identified was the simian (monkey) immunodeficiency virus that was known to infect chimpanzees (SIVcpz), but this virus had significant differences between it and HIV.

So what happened in 1999? Are chimpanzees now known to be the source of HIV?

In February 1999 it was announced that a group of researchers from the University of Alabama had studied frozen tissue from a chimpanzee and found that the simian virus it carried (SIVcpz) was almost identical to HIV-1. The chimpanzee came from a sub-group of chimpanzees known as Pan troglodytes, which were once common in west-central Africa.

It is claimed by the researchers that this shows that these chimpanzees were the source of HIV-1, and that the virus at some point crossed species from chimpanzees to human. However, it is not necessarily clear that chimpanzees are the original reservoir for HIV-1 because chimpanzees are only rarely infected with SIVcpz. It is therefore possible that both chimpanzees and humans have been infected from a third, as yet unidentified, primate species. In either case at least two separate transfers into the human population would have been required.

How could HIV have crossed species?

It has been known for a long time that certain viruses can pass from animals to humans, and this process is referred to as Zoonosis.

The researchers from the University of Alabama have suggested that HIV could have crossed over from chimpanzees as a result of a human killing a chimp and eating it for food.

Some other rather controversial theories have contended that HIV was transferred iatrogenically i.e. via medical experiments. One particularly well-publicised theory is that polio vaccines played a role in the transfer, as the vaccines were prepared using monkey kidneys. In February 2000 it was announced that the Wistar Institute in Philadelphia had discovered in its stores a phial of polio vaccine that had been used as part of a polio vaccination programme in the Belgian Congo in the 1950's.It was planned to test this vaccine for the presence of HIV.

But crucial to the credibility of any of these alternative theories is the question of when the transfer took place.

Is there any evidence of when the transfer took place?

During the last few years it has become possible not only to determine whether HIV is present in a blood or plasma sample, but also to determine the particular subtype of the virus. Studying the subtype of virus of some of the earliest known instances of HIV infection can help to provide clues about the time of origin and the subsequent evolution of HIV in humans. Three of the earliest known instances of HIV infection are as follows:

A plasma sample taken in 1959 from an adult male living in what is now the Democratic Republic of Congo.
HIV found in tissue samples from an African-American teenager who died in St. Louis in 1969.
HIV found in tissue samples from a Norwegian sailor who died around 1976.

Analysis in 1998 of the plasma sample from 1959 was interpreted as suggesting that HIV-1 was introduced into humans around the 1940s or the early 1950s, which was earlier than had previously been suggested. Other scientists have suggested that it could have been even longer, perhaps around 100 years or more ago.

In January 2000, the results of a new study presented at the 7th Conference on Retroviruses and Opportunistic Infections, suggested that the first case of HIV infection occurred around 1930 in West Africa. Dr. Bette Korber of the Los Alamos National Laboratory carried out the study. The estimate of 1930 (which does have a 20 year margin of error) is based on a complicated computer model of HIV's evolution.

Is it known where the emergence of HIV in humans took place?

Many people now assume that because HIV has apparently developed from a form of SIV found in a type of chimpanzee in West Africa, that is was actually in West Africa that HIV first emerged in humans. It is then presumed that HIV spread from there around the world. However, as discussed above, chimpanzees are not necessarily the original source of HIV and it is likely that the virus crossed over to humans on more than one occasion. So it is quite possible that HIV emerged at the same time in say both South America and Africa, or that it even emerged in the America before it emerged in Africa. We will probably never know exactly when and where the virus first emerged, but what is clear is that sometime in the middle of the 20th century, HIV infection in humans developed into the epidemic of disease around the world that we now refer to as AIDS.

What caused the epidemic to spread so suddenly?

There are a number of factors that may have contributed to the sudden spread including international travel, the blood industry, and widespread drug use.

International Travel: The role of international travel in the spread of HIV was highlighted by the case of 'Patient Zero' . Patient Zero was a Canadian flight attendant called Gaetan Dugas who traveled extensively worldwide. Analysis of several of the early cases of AIDS showed that the infected individuals were either direct or indirect sexual contacts of the flight attendant. These cases could be traced to several different American cities demonstrating the role of international travel in spreading the virus. It also suggested that the disease was probably the consequence of a single transmissible agent.
The Blood Industry: As blood transfusions became a routine part of medical practice, this led to a growth of an industry for meeting this increased demand for blood. In some countries such as the USA paid donors were used, including intravenous drug users. This blood was then sent worldwide. Also, in the late 1960's hemophiliacs began to benefit from the blood clotting properties of a product called Factor VIII. However, to produce the coagulant, blood from thousands of individual donors had to be pooled. Factor VIII was then distributed worldwide making it likely that hemophiliacs could become exposed to new infections.
Drug Use: The 1970s saw an increase in the availability of heroin following the Vietnam War and other conflicts in the Middle East, which helped stimulate a growth in intravenous drug use. This increased availability together with the development of disposable plastic syringes and the establishment of 'shooting galleries' where people could buy drugs and rent equipment provided another route through which the virus could be passed on.

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What is the difference between HIV-1 and HIV-2?

There are currently two types of HIV: HIV-1 and 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. Both HIV-1 and HIV-2 are transmitted by sexual contact, through blood, and from mother to child, and they appear to cause clinically indistinguishable AIDS.

However, HIV-2 is less easily transmitted, and the period between initial infection and illness is longer in the case of HIV-2.

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How many subtypes of HIV-1 are there?

HIV-1 is a highly variable virus, which mutates very readily. So there are many different strains of HIV-1. These strains can be classified according to groups and subtypes and there are two groups, group M and group O .

In September 1998, French researchers announced that they had found a new strain of HIV in a woman from Cameroon in West Africa. The strain does not belong to either group M or group O, and has only been found in three other people, all in the Cameroon.

Within group M there are currently known to be at least 10 genetically distinct subtypes of HIV-1. These are subtypes A to J. In addition, Group O contains another distinct group of very heterogeneous viruses. The subtypes of group M may differ as much between subtypes as group M differs from group O.

Where are the different subtypes found?

The subtypes are very unevenly distributed throughout the world.

For instance:

Subtype B is mostly found in the Americas, Japan, Australia, the Caribbean and Europe.
Subtypes A and D predominate in sub-Saharan Africa.
Subtype C in South Africa and India.
Subtype E in Central African Republic. Thailand and other countries of Southeast Asia.
Subtypes F- Brazil and Romania.
Subtypes G and H Russia and Central Africa.
Subtypes I (Cyprus).
and group O (Cameroon) are of very low prevalence.
In Africa, most subtypes are found, although subtype B is less prevalent.

What are the major differences between these subtypes?

The major difference is their genetic composition; biological differences observed in vitro and/or in vivo may reflect this.

It has also been suggested that certain subtypes may be predominantly associated with specific modes of transmission: for example, subtype B with homosexual contact and intravenous drug use (essentially via blood) and subtypes E and C, with heterosexual transmission (via a mucosal route).

Laboratory studies undertaken by Dr. Max Essex of the Harvard School of Public Health in Boston have demonstrated that subtypes C and E infect and replicate more efficiently than subtype B in Langerhans cells which are present in the vaginal mucosa, cervix and the foreskin of the penis but not on the wall of the rectum.These data suggest that HIV subtypes E and C may have a higher potential for heterosexual transmission than subtype B.

However, caution should be exercised in applying in vitro-studies to real-life situations. Other variables, which affect the risk of transmission, such as the stage of HIV disease, the frequency of exposure, condom use, and the presence of other STIs, and other Opportunistic infections must also be taken into consideration before any definite conclusions can be drawn.

Are some subtypes more infectious than others?

Some recent studies have suggested that subtype E spreads more easily than subtype B. In one study conducted in Thailand , it was found that the transmission rate of subtype E among female commercial sex workers and their clients was higher than that for subtype B found among a general population in North America.

In a second study conducted in Thailand , among 185 couples with one partner infected with HIV subtypes E or B, it was found that the probability of both partners in a couple becoming infected was higher for subtype E (69%) than for subtype B (48%). This suggests that subtype E may be more easily transmissible. However, it is important to note that neither study was designed to fully control for multiple variables, which may affect the risk of transmission.

Is subtype E a new subtype?

Subtype E is not new. Stored blood samples show that subtype E was already identified at the beginning of the epidemic in Central Africa and as early as 1989 in Thailand.

Do conventional HIV antibody tests detect all subtypes?

Routine HIV antibody tests which are currently being used for blood screening and diagnostic purposes detect virtually all subtypes of the HIV. (Most companies have modified their assays so that they detect the newly identified HIV-1 group O strains.)

Are more subtypes likely to "appear"?

It is almost certain that new HIV genetic subtypes will be discovered in the future, and indeed that new subtypes will develop as virus mutation continues to occur. The current subtypes will also continue to spread to new areas as the global epidemic continues. However, in some countries there is very little monitoring undertaken to detect new subtypes. For example, in Britain, the government's Public Health Laboratory Service, which is responsible for monitoring the spread of HIV in Britain, only analyses two new infections a month for subtype information.

What are the implications of HIV variability for research on treatment?

More research needs to be undertaken. Some HIV subtypes have been observed in the laboratory to have different growth and immunological characteristics.It is not known whether the genetic variations in subtype E or other subtypes actually make a difference in terms of the risk of transmission or the response to antiviral therapy.

The Acquired ImmunoDeficiency syndrome (AIDS) was first recognized in 1981 and has since become a major worldwide epidemic. AIDS is caused by the human immunodeficiency virus (HIV). By leading to the destruction and/or functional impairment of cells of the immune system, notably CD4+ T cells, HIV progressively destroys the body's ability to fight infections and certain cancers.