AIDS origin - AbsoluteAstronomy.com

AIDS is caused by the Human immunodeficiency virus (HIV), which originated in non-human primate

Primate

A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

s in Sub-Saharan Africa

Sub-Saharan Africa

Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...

and was transferred to humans during the late 19th or early 20th century.

Two types of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent, is more easily transmitted and is the cause of the vast majority of HIV infections globally. The pandemic strain of HIV-1 is closely related to a virus found in the chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s of the subspecies Pan troglodytes troglodytes, which lives in the forests of the Central African nations of Cameroon

Cameroon

Cameroon, officially the Republic of Cameroon , is a country in west Central Africa. It is bordered by Nigeria to the west; Chad to the northeast; the Central African Republic to the east; and Equatorial Guinea, Gabon, and the Republic of the Congo to the south. Cameroon's coastline lies on the...

, Equatorial Guinea, Gabon

Gabon

Gabon , officially the Gabonese Republic is a state in west central Africa sharing borders with Equatorial Guinea to the northwest, Cameroon to the north, and with the Republic of the Congo curving around the east and south. The Gulf of Guinea, an arm of the Atlantic Ocean is to the west...

, Republic of Congo (or Congo-Brazzaville), and Central African Republic

Central African Republic

The Central African Republic , is a landlocked country in Central Africa. It borders Chad in the north, Sudan in the north east, South Sudan in the east, the Democratic Republic of the Congo and the Republic of the Congo in the south, and Cameroon in the west. The CAR covers a land area of about ,...

. HIV-2 is less transmittable and is largely confined to West Africa, along with its closest relative, a virus of the sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

(Cercocebus atys atys), an Old World monkey inhabiting southern Senegal

Senegal

Senegal , officially the Republic of Senegal , is a country in western Africa. It owes its name to the Sénégal River that borders it to the east and north...

, Guinea-Bissau, Guinea

Guinea

Guinea , officially the Republic of Guinea , is a country in West Africa. Formerly known as French Guinea , it is today sometimes called Guinea-Conakry to distinguish it from its neighbour Guinea-Bissau. Guinea is divided into eight administrative regions and subdivided into thirty-three prefectures...

, Sierra Leone, Liberia

Liberia

Liberia , officially the Republic of Liberia, is a country in West Africa. It is bordered by Sierra Leone on the west, Guinea on the north and Côte d'Ivoire on the east. Liberia's coastline is composed of mostly mangrove forests while the more sparsely populated inland consists of forests that open...

, and western Ivory Coast.

Transmission from non-human to human populations

Most HIV researchers agree that HIV evolved at some point from the closely related Simian immunodeficiency virus

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

(SIV), and that SIV or HIV (post mutation) was transferred from non-human primates to humans in the recent past (as a type of zoonosis

Zoonosis

A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...

). Research in this area is conducted using molecular phylogenetics, comparing viral genomic sequences to determine relatedness.

HIV-1 transmission from chimpanzees and gorillas to humans

Scientists generally accept that the known strains (or groups) of HIV-1 are most closely related to the simian immunodeficiency viruses (SIVs) endemic in wild ape

Ape

Apes are Old World anthropoid mammals, more specifically a clade of tailless catarrhine primates, belonging to the biological superfamily Hominoidea. The apes are native to Africa and South-east Asia, although in relatively recent times humans have spread all over the world...

populations of West Central African forests. Particularly, each of the known HIV-1 strains is either closely related to the SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

that infects the chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

subspecies Pan troglodytes troglodytes (SIVcpz), or to the SIV that infects Western lowland gorilla

Western Lowland Gorilla

The western lowland gorilla is a subspecies of the western gorilla that lives in montane, primary, and secondary forests and lowland swamps in Angola, Cameroon, Central African Republic, Congo, Democratic Republic of the Congo, Equatorial Guinea and Gabon. It is the gorilla usually found in zoos...

s (Gorilla gorilla gorilla), called SIVgor. The pandemic HIV-1 strain (group M or Main) and a very rare strain only found in a few Cameroonian people (group N) are clearly derived from SIVcpz strains endemic in Pan troglodytes troglodytes chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

populations living in Cameroon

Cameroon

. Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of the same country. Finally, the primate ancestor of HIV-1 group O, a strain infecting tens of thousands of people mostly from Cameroon

Cameroon

but also from neighboring countries, is still uncertain, but there is evidence that it is either SIVcpz or SIVgor. The pandemic HIV-1 group M is most closely related to the SIVcpz collected from the southeastern rain forests of Cameroon

Cameroon

(modern East Province

East Province (Cameroon)

The East Region occupies the southeastern portion of the Republic of Cameroon. It is bordered to the east by the Central African Republic, to the south by Congo, to the north by the Adamawa Region, and to the west by the Centre and South Regions...

) near the Sangha River

Sangha River

The Sangha River, a river in central Africa, is a tributary of the Congo River, which it joins at . Formed by the merging of the Mambéré River into the Kadéï River at Nola , the Sangha flows through the Central African Republic, along the border of Cameroon, and through the Republic of Congo.Its...

. Thus, this region is presumably where the virus was first transmitted from chimpanzees to humans. However, reviews of the epidemiological evidence of early HIV-1 infection in stored blood samples, and of old cases of AIDS in Central Africa have led many scientists to believe that HIV-1 group M early human epicenter was probably not in Cameroon

Cameroon

, but rather farther south in the Democratic Republic of the Congo

Democratic Republic of the Congo

The Democratic Republic of the Congo is a state located in Central Africa. It is the second largest country in Africa by area and the eleventh largest in the world...

, more probably in its capital city, Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

.

Using HIV-1 sequences preserved in human biological samples along with estimates of viral mutation rates, scientists calculate that the jump from chimpanzee to human probably happened during the late 19th or early 20th century, a time of rapid urbanisation and colonisation in equatorial Africa. Exactly when the zoonosis

Zoonosis

occurred is not known. Some molecular datation studies suggest that HIV-1 group M had its most recent common ancestor

Most recent common ancestor

In genetics, the most recent common ancestor of any set of organisms is the most recent individual from which all organisms in the group are directly descended...

(MRCA) (that is, started to spread in the human population) in the early 20th century, probably between 1915 and 1941. A study published in 2008, analyzing viral sequences recovered from a recently-discovered biopsy made in Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

, in 1960, along with previously-known sequences, suggested a common ancestor between 1873 and 1933 (with central estimates varying between 1902 and 1921).

Genetic recombination

Genetic recombination

Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...

had earlier been thought to "seriously confound" such phylogenetic analysis, but later "work has suggested that recombination is not likely to systematically bias [results]", although recombination is "expected to increase variance". The results of a 2008 phylogenetics study support the later work and indicate that HIV evolves "fairly reliably".

HIV-2 transmission from sooty mangabeys to humans

Similar researches were undertaken with SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

strains collected from several wild sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

(Cercocebus atys atys) (SIVsmm) communities of the West African nations of Sierra Leone

Sierra Leone

Sierra Leone , officially the Republic of Sierra Leone, is a country in West Africa. It is bordered by Guinea to the north and east, Liberia to the southeast, and the Atlantic Ocean to the west and southwest. Sierra Leone covers a total area of and has an estimated population between 5.4 and 6.4...

, Liberia, and Ivory Coast. The resulting phylogenetic analyses show that the viruses most closely related to the two strains of HIV-2 which spread considerably in humans (HIV-2 groups A and B) are the SIVsmm found in the sooty mangabeys of the Tai forest, in western Ivory Coast.

There are six additional known HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

s to humans. Groups C and D have been found in two people from Liberia

Liberia

, groups E and F have been discovered in two people from Sierra Leone

Sierra Leone

, and groups G and H have been detected in two people from the Ivory Coast. These HIV-2 strains are probably dead end infections, and each of them is most closely related to SIVsmm strains from sooty mangabeys living in the same country where the human infection was found.

Molecular datation studies suggest that both the epidemic groups (A and B) started to spread among humans between 1905 and 1961 (with the central estimates varying between 1932 and 1945).
See also this article about HIV types, groups, and subtypes.

Bushmeat practice as the most plausible cause

According to the natural transfer theory (also called 'Hunter Theory' or 'Bushmeat Theory'), the "simplest and most plausible explanation for the cross-species transmission" of SIV or HIV (post mutation), the virus was transmitted from an ape

Ape

or monkey

Monkey

A monkey is a primate, either an Old World monkey or a New World monkey. There are about 260 known living species of monkey. Many are arboreal, although there are species that live primarily on the ground, such as baboons. Monkeys are generally considered to be intelligent. Unlike apes, monkeys...

to a human when a hunter or bushmeat

Bushmeat

Bushmeat initially referred to the hunting of wild animals in West and Central Africa and is a calque from the French viande de brousse. Today the term is commonly used for meat of terrestrial wild animals, killed for subsistence or commercial purposes throughout the humid tropics of the Americas,...

vendor/handler was bitten or cut while hunting or butchering the animal. The resulting exposure to blood or other bodily fluids of the animal can result in SIV infection. A recent serological survey showed that human infections by SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

are not rare in Central Africa: the percentage of people showing seroreactivity to antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s – evidence of current or past SIV infection – was 2.3% among the general population of Cameroon

Cameroon

, 7.8% in villages where bushmeat is practiced, and 17.1% in the most exposed people of these villages. How the SIV virus would have transformed into HIV after infection of the hunter or bushmeat

Bushmeat

handler from the ape/monkey is still a matter of debate, although natural selection would favor any virions capable of adjusting so that they could infect and reproduce in the T cells of a human host.

Conditions for successful zoonosis

Zoonosis

(transfer of a pathogen

Pathogen

A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

from non-human animals to humans) and subsequent spread of the pathogen between humans, requires the following conditions:

a human population;
a nearby population of a host animal;
an infectious pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

in the host animal that can spread from animal to human;
interaction between the species to transmit enough of the pathogen to humans to establish a human foothold, which could have taken millions of individual exposures;
ability of the pathogen to spread from human to human (perhaps acquired by mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

);
some process allowing the pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

to disperse widely, preventing the infection from "burning out" by either killing off its human hosts or provoking immunity in a local population of humans.

The unresolved issues about HIV origins and emergence

It is clear that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and SIVsmm viruses, and that bushmeat practice provides the most plausible venue for cross-species transfer to humans. However, some loose ends remain unresolved.

It is not yet explained why only four HIV groups (HIV-1 groups M and O, and HIV-2 groups A and B) spread considerably in human populations, despite bushmeat

Bushmeat

practices being very widespread in Central and West Africa, and the resulting human SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

infections being common.

It remains also unexplained why all epidemic HIV groups emerged in humans nearly simultaneously, and only in the 20th century, despite very old human exposure to SIV (a recent phylogenetic study demonstrated that SIV is at least tens of thousands of years old).

The discovery of the main HIV / SIV phylogenetic relationships permits to explain broadly HIV biogeography

Biogeography

Biogeography is the study of the distribution of species , organisms, and ecosystems in space and through geological time. Organisms and biological communities vary in a highly regular fashion along geographic gradients of latitude, elevation, isolation and habitat area...

: the early epicenters of the HIV-1 groups were in Central Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses (chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s and gorilla

Gorilla

Gorillas are the largest extant species of primates. They are ground-dwelling, predominantly herbivorous apes that inhabit the forests of central Africa. Gorillas are divided into two species and either four or five subspecies...

s) exist; similarly, the HIV-2 groups had their epicenters in West Africa, where sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

s, which harbor the related SIVsmm virus, exist. However these relationships do not explain more detailed patterns of biogeography, such as why epidemic HIV-2 groups (A and B) only evolved in the Ivory Coast, which is only one of six countries harboring the sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

. It is also unclear why the SIVcpz endemic in the chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

subspecies Pan troglodytes schweinfurthii (inhabiting the Democratic Republic of Congo, Central African Republic, Rwanda

Rwanda

Rwanda or , officially the Republic of Rwanda , is a country in central and eastern Africa with a population of approximately 11.4 million . Rwanda is located a few degrees south of the Equator, and is bordered by Uganda, Tanzania, Burundi and the Democratic Republic of the Congo...

, Burundi, Uganda

Uganda

Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...

, and Tanzania

Tanzania

The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

) did not spawn an epidemic HIV-1 strain to humans, while the Democratic Republic of Congo was the main epicenter of HIV-1 group M, a virus descended from SIVcpz strains of a subspecies (Pan troglodytes troglodytes) that does not exist in this country.

Theories of HIV origin and epidemic emergence

Several of the theories of HIV origin put forward (described below) attempt to explain the unresolved loose ends described in the previous section. Most of them accept the (above described) established knowledge of the HIV/SIV phylogenetic relationships, and also accept that bushmeat

Bushmeat

practice was the most likely cause of the initial transfer to humans. All of them propose that the simultaneous epidemic emergences of four HIV groups in the late 19th-early 20th century, and the lack of previous emergences, are explained by new factor(s) that appeared in the relevant African regions in that timeframe. These new factor(s) would have acted either to increase human exposures to SIV, to help it to adapt to the human organism by mutation

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

(thus enhancing its between-humans transmissibility), or to cause an initial burst of transmissions crossing an epidemiological threshold, and therefore increasing the odds of continued spread.

Social changes and urbanization

It was proposed by Beatrice Hahn, Paul Sharp, and colleagues that "[the epidemic emergence of HIV] most likely reflects changes in population structure and behaviour in Africa during the 20th century and perhaps medical interventions that provided the opportunity for rapid human-to-human spread of the virus". After the Scramble for Africa

Scramble for Africa

The Scramble for Africa, also known as the Race for Africa or Partition of Africa was a process of invasion, occupation, colonization and annexation of African territory by European powers during the New Imperialism period, between 1881 and World War I in 1914...

started in the 1880s, European colonial powers established cities, towns, and other colonial stations. A largely masculine labor force was hastily recruited to work in fluvial and sea ports, railways, other infrastructures, and in plantations. This disrupted traditional tribal values, and favored sexual promiscuity. In the nascent cities women felt relatively liberated from rural tribal rules and many remained unmarried or divorced during long periods, this being very rare in African traditional societies. This was accompanied by unprecedented increase in people's movements.

Michael Worobey and colleagues observed that the growth of cities had probably a role in the epidemic emergence of HIV, since the phylogenetic datations of the two older strains of HIV-1 (groups M and O), suggest that these viruses started to spread soon after the main Central African colonial cities were founded.

Clearly, there is a constellation of factors associated with the social changes prompted by colonialism

Colonialism

Colonialism is the establishment, maintenance, acquisition and expansion of colonies in one territory by people from another territory. It is a process whereby the metropole claims sovereignty over the colony and the social structure, government, and economics of the colony are changed by...

that could have helped HIV to start to spread by the sexual route, establishing successful epidemics: urbanization, increased trade, a currency-based economy, behavioral changes, singlehood, sexual promiscuity, and increased movements of people.

Heart of Darkness

Amit Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged epidemically as a result of the harsh conditions, forced labor, displacement, and unsafe injection and vaccination

Vaccination

Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

practices associated with colonialism

Colonialism

, particularly in French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

. The workers in plantations, construction projects, and other colonial enterprises were supplied with bushmeat

Bushmeat

, this contributing to increase this activity, and then exposures to SIV. Several historical sources support the view that bushmeat

Bushmeat

hunting indeed increased, both because of the necessity to supply workers and because projectile-firing weapons proliferated.

The colonial authorities also gave many vaccination

Vaccination

s against smallpox

Smallpox

Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

, and injections, of which many would be made without sterilising the equipment between uses (unsafe or unsterile injections). Chitnis et al. proposed that both these parenteral

Parenteral

Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...

risks and the prostitution associated with forced labor camps could have caused serial transmission (or serial passage

Serial passage

Serial passage is a virus attenuation technique developed originally by Louis Pasteur in the 1880s. It is similar to selective breeding, and can be used to create an attenuated strain of a virus to develop vaccines, or to increase the virulence of a viral strain in order to create epidemics.The...

) of SIV between humans (see discussion of this in the next section). In addition, they proposed that the conditions of extreme stress associated with forced labor could depress the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

of workers, therefore prolonging the primary acute infection

Acute HIV infection

Acute HIV infection or primary HIV infection is the second stage of HIV infection. It occurs after the incubation stage, before the latency stage and the potential AIDS succeeding the latency stage....

period of someone newly infected by SIV, thus increasing the odds of both adaptation of the virus to humans, and of further transmissions.

The authors predicted that HIV-1 originated in the area of French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

, and in the early 20th century (when the colonial abuses and forced labor were at their peak). Later researches proved these predictions mostly correct: HIV-1 groups M and O started to spread in humans in late 19th–early 20th century. And all groups of HIV-1 descend from either SIVcpz or SIVgor from ape

Ape

s living to the west of the Ubangi River

Ubangi River

The Ubangi River , also spelled Oubangui, is the largest right-bank tributary of the Congo River of Central Africa. It begins at the confluence of the Mbomou and Uele Rivers and flows west, then bends to the southwest and passes through Bangui, after which it flows south to the Congo at Liranga....

, either in countries which belonged to the French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

federation of colonies, in Equatorial Guinea

Equatorial Guinea

Equatorial Guinea, officially the Republic of Equatorial Guinea where the capital Malabo is situated.Annobón is the southernmost island of Equatorial Guinea and is situated just south of the equator. Bioko island is the northernmost point of Equatorial Guinea. Between the two islands and to the...

(then a Spanish colony), or in Cameroon

Cameroon

(which was a German colony between 1884 and 1916, then fell to Allied forces in World War I, and had most of its area administered by France, in close association with French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

).

This theory was later dubbed 'Heart of Darkness' by Jim Moore, alluding to the book of the same title

Heart of Darkness

Heart of Darkness is a novella written by Joseph Conrad. Before its 1903 publication, it appeared as a three-part series in Blackwood's Magazine. It was classified by the Modern Library website editors as one of the "100 best novels" and part of the Western canon.The story centres on Charles...

written by Joseph Conrad

Joseph Conrad

Joseph Conrad was a Polish-born English novelist.Conrad is regarded as one of the great novelists in English, although he did not speak the language fluently until he was in his twenties...

, the main focus of which is colonial abuses in equatorial Africa.

Unsterile injections

In several articles published since 2001, Preston Marx, Philip Alcabes, and Ernest Drucker proposed that HIV emerged because of rapid serial human-to-human transmission of SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

(after a bushmeat

Bushmeat

hunter or handler became SIV-infected) through unsafe or unsterile injections. Although both Chitnis et al. and Sharp et al. also suggested that this may have been one of the major risk factors at play in HIV emergence (see above), Marx et al. enunciated the underlying mechanisms in greater detail, and wrote the first review of the injection campaigns made in colonial Africa.

Central to Marx et al. argument is the concept of adaptation by serial passage

Serial passage

(or serial transmission): an adventitious virus (or other pathogen

Pathogen

) can increase its biological adaptation

Adaptation

An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....

to a new host species if it is rapidly transmitted between hosts, while each host is still in the acute infection

Acute HIV infection

period. This process favors the accumulation of adaptive mutation

Adaptive mutation

Evolutionary theory describes that mutagenesis occurs randomly, regardless of the utility of a genetic mutation to the organism. If it is beneficial or neutral, the organism will survive to reproduce and pass on the mutation...

s more rapidly, therefore increasing the odds that a better adapted viral variant will appear in the host before the immune system

Immune system

suppresses the virus. Such better adapted variant could then survive in the human host for longer than the short acute infection

Acute HIV infection

period, in high numbers (high viral load

Viral load

Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...

), which would grant it more possibilities of epidemic spread.

Marx et al. reported experiments of cross-species transfer of SIV in captive monkeys (some of which made by themselves), in which the use of serial passage

Serial passage

helped to adapt SIV to the new monkey species after passage by three or four animals.

In agreement with this model is also the fact that, while both HIV-1 and HIV-2 attain substantial viral load

Viral load

s in the human organism, adventitious SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

infecting humans seldom does so: people with SIV antibodies often have very low or even undetectable SIV viral load

Viral load

. This suggests that both HIV-1 and HIV-2 are adapted to humans, and serial passage

Serial passage

could have been the process responsible for it.

Marx et al. proposed that unsterile injections (that is, injections where the needle or syringe is reused without sterilization or cleaning between uses), which were likely very prevalent in Africa, during both the colonial period and afterwards, provided the mechanism of serial passage

Serial passage

that permitted HIV to adapt to humans, therefore explaining why it emerged epidemically only in the 20th century.

Massive injections of the antibiotic era

Marx et al. emphasize the massive number of injections administered in Africa after antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s were introduced (around 1950) as being the most likely implicated in the origin of HIV because, by these times (roughly in the period 1950 to 1970), injection intensity in Africa was maximal. They argued that a serial passage

Serial passage

chain of 3 or 4 transmissions between humans is an unlikely event (the probability of transmission after a needle reuse is something between 0.3% and 2%, and only a few people have an acute SIV infection at any time), and so HIV emergence may have required the very high frequency of injections of the antibiotic

Antibiotic

era.

The molecular datation studies place the initial spread of the epidemic HIV groups before that time (see above). According to Marx et al., these studies could have overestimated the age of the HIV groups, because they depend on a molecular clock

Molecular clock

The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...

assumption, may not have accounted for the effects of natural selection

Natural selection

Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

in the viruses, and the serial passage

Serial passage

process alone would be associated with strong natural selection

Natural selection

The injection campaigns against sleeping sickness

David Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis

Trypanosomiasis

Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus Trypanosoma. Approximately 500,000 men, women and children in 36 countries of sub-Saharan Africa suffer from human African trypanosomiasis which is caused by...

(sleeping sickness) in Central Africa were responsible for the emergence of HIV-1. Unlike Marx et al., Gisselquist argued that the millions of unsafe injections administered during these campaigns were sufficient to spread rare HIV infections into an epidemic, and that evolution of HIV through serial passage

Serial passage

was not essential to the emergence of the HIV epidemic in the 20th century.

This theory focuses on injection campaigns that peaked in the period 1910—40, that is, around the time the HIV-1 groups started to spread. It also focuses on the fact that many of the injections in these campaigns were intravenous (which are more likely to transmit SIV/HIV than subcutaneous or intramuscular injections), and many of the patients received many (often more than 10) injections per year, therefore increasing the odds of SIV serial passage

Serial passage

Other early injection campaigns

Jacques Pépin and Annie-Claude Labbé reviewed the colonial health reports of Cameroon

Cameroon

and French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

for the period 1921—59, calculating the incidences of the diseases requiring intravenous injections. They concluded that trypanosomiasis

Trypanosomiasis

, leprosy

Leprosy

Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...

, yaws

Yaws

Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...

, and syphilis

Syphilis

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

were responsible for most intravenous injections. Schistosomiasis

Schistosomiasis

Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...

, tuberculosis

Tuberculosis

Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

, and vaccinations against smallpox

Smallpox

represented lower parenteral

Parenteral

Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...

risks: schistosomiasis cases were relatively few; tuberculosis patients only became numerous after mid century; and there were few smallpox vaccinations in the lifetime of each person.

The authors suggested that the very high prevalence of the Hepatitis C

Hepatitis C

Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

virus in southern Cameroon

Cameroon

and forested areas of French Equatorial Africa

French Equatorial Africa

French Equatorial Africa or the AEF was the federation of French colonial possessions in Middle Africa, extending northwards from the Congo River to the Sahara Desert.-History:...

(around 40—50%) can be better explained by the unsterile injections used to treat yaws

Yaws

Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...

, because this disease was much more prevalent than syphilis

Syphilis

, trypanosomiasis

Trypanosomiasis

, and leprosy

Leprosy

in these areas. They suggested that all these parenteral risks caused, not only the massive spread of Hepatitis C

Hepatitis C

, but also the spread of other pathogen

Pathogen

s, and the emergence of HIV-1: "the same procedures could have exponentially amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz to several thousand patients treated with arsenicals or other drugs, a threshold beyond which sexual transmission could prosper." They do not suggest specifically serial passage

Serial passage

as the mechanism of adaptation.

According to Pépin's 2011 book, The Origins of AIDS, the virus can be traced to a central African bush hunter in 1921, with colonial medical campaigns playing a key role in enabling a future epidemic. Pépin also claims that the virus was brought to the Americas by a Haitian teacher returning home from Zaire in the 1960s.

Genital ulcer diseases and sexual promiscuity

João Dinis de Sousa, Viktor Müller, Philippe Lemey, and Anne-Mieke Vandamme proposed that HIV became epidemic through sexual serial transmission, in nascent colonial cities, helped by a high frequency of genital ulcer

Genital ulcer

A Genital ulcer is an ulcer located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or thrush. Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated...

s, caused by genital ulcer diseases (GUD). GUD are simply sexually transmitted disease

Sexually transmitted disease

Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...

s that cause genital ulcers; examples are syphilis

Syphilis

, chancroid

Chancroid

Chancroid is a sexually transmitted infection characterized by painful sores on the genitalia...

, lymphogranuloma venereum

Lymphogranuloma venereum

Lymphogranuloma venereum is a sexually transmitted disease caused by the invasive serovars L1, L2, L2a or L3 of Chlamydia trachomatis....

, and genital herpes. These diseases increase the probability of HIV transmission dramatically, from around 0.01—0.1% to 4—43% per heterosexual act, because the genital ulcers provide a portal of viral entry, and contain many activated T cell

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s expressing the CCR5

CCR5

C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins...

co-receptor, the main cell targets of HIV.

The probable time interval of cross-species transfer

Sousa et al. use molecular datation techniques to estimate the time when each HIV group split from its closest SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

lineage. Each HIV group necessarily crossed to humans between this time and the time when it started to spread (the time of the MRCA

Most recent common ancestor

In genetics, the most recent common ancestor of any set of organisms is the most recent individual from which all organisms in the group are directly descended...

), because after the MRCA certainly all lineages were already in humans, and before the split with the closest simian

Simian

The simians are the "higher primates" familiar to most people: the Old World monkeys and apes, including humans, , and the New World monkeys or platyrrhines. Simians tend to be larger than the "lower primates" or prosimians.- Classification and evolution :The simians are split into three groups...

strain, the lineage was in a simian. HIV-1 groups M and O, split from their closest SIVs around 1876 (1847—1907), 1741 (1606—1870), respectively. HIV-2 did so around 1889 (1856—1922). This information, together with the datations of the HIV groups' MRCA

MRCA

MRCA may refer to:*Member of the Royal College of Anaesthetists, post-nominal letters awarded on completion of the primary FRCA examination and 12 months specialist training...

s (described above) mean that all HIV groups likely crossed to humans in late 19th—early 20th century.

Strong GUD incidence in nascent colonial cities

The authors reviewed colonial medical articles and archived medical reports of the countries at or near the ranges of chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s, gorilla

Gorilla

s and sooty mangabey

Sooty Mangabey

The sooty mangabey is an Old World monkey found in forests from Senegal east to Ghana. It is famous for being believed to be the monkey that HIV-2 might have originated in before jumping species...

s, and found that genital ulcer diseases peaked in the colonial cities during their early growth period (up to 1935). The colonial authorities recruited men to work in railways, fluvial and sea ports, and other infrastructure projects, and most of these men did not bring their wives with them. Then, the highly male-biased sex ratio

Sex ratio

Sex ratio is the ratio of males to females in a population. The primary sex ratio is the ratio at the time of conception, secondary sex ratio is the ratio at time of birth, and tertiary sex ratio is the ratio of mature organisms....

favoured prostitution, which in its turn caused an explosion of GUD (especially syphilis

Syphilis

and chancroid

Chancroid

Chancroid is a sexually transmitted infection characterized by painful sores on the genitalia...

). After the mid-1930s, people's movements were more tightly controlled, and mass surveys and treatments (of arsenical

Arsenical

An arsenical is a arsenic-containing compound.Examples include:* arsanilic acid* arsenamide* arsenates* arsenites* arsphenamine* p-azobenzenearsonate* cacodylic acid* melarsoprol* roxarsone...

s and other drugs) were organized, and so the GUD incidences started to decline. They declined even further after World War II, because of the heavy use of antibiotic

Antibiotic

s, so that, by the late 1950s, Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

(which is the probable epicenter of HIV-1 group M) had a very low GUD incidence. Similar processes happened in the cities of Cameroon

Cameroon

and Ivory Coast, where HIV-1 group O and HIV-2 respectively evolved.

Therefore, the peak GUD incidences in cities have a good temporal coincidence with the period when all main HIV groups crossed to humans and started to spread. In addition, the authors gathered evidence that syphilis

Syphilis

and the other GUDs were, like injections, absent from the densely forested areas of Central and West Africa before organized colonialism

Colonialism

socially disrupted these areas (starting in the 1880s). Thus, this theory also potentially explains why HIV emerged only after late 19th century.

Male circumcision distribution and HIV origins

Male circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

may reduce the probability of HIV acquisition by men (see article Circumcision and HIV

Circumcision and HIV

Over forty epidemiological studies have been conducted to investigate the relationship between male circumcision and HIV infection. Reviews of these studies have reached differing conclusions about whether circumcision could be used as a prevention method against HIV.Experimental evidence was...

). Leaving aside blood transfusion

Blood transfusion

Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

s, the highest HIV-1 transmissibility ever measured was from GUD-suffering female prostitutes to uncircumcised men—the measured risk was 43% in a single sexual act. Sousa et al. reasoned that the adaptation and epidemic emergence of each HIV group may have required such extreme conditions, and thus reviewed the existing ethnographic

Ethnography

Ethnography is a qualitative method aimed to learn and understand cultural phenomena which reflect the knowledge and system of meanings guiding the life of a cultural group...

literature for patterns of male circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

and hunting of ape

Ape

s and monkey

Monkey

s for bushmeat

Bushmeat

, focusing on the period 1880—1960, and on most of the 318 ethnic group

Ethnic group

An ethnic group is a group of people whose members identify with each other, through a common heritage, often consisting of a common language, a common culture and/or an ideology that stresses common ancestry or endogamy...

s living in Central and West Africa. They also collected censuses and other literature showing the ethnic composition of colonial cities in this period. Then, they estimated the circumcision frequencies of the Central African cities over time.

Circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

is nowadays almost universal in almost all countries of Central and West Africa.
However, Sousa et al. charts reveal that male circumcision frequencies were much lower in several cities of these areas in early 20th century. The reason is that many ethnic group

Ethnic group

s not performing circumcision by that time gradually adopted it, to imitate other ethnic groups and enhance the social acceptance of their boys (colonialism

Colonialism

produced massive intermixing between African ethnic groups). About 15—30% of men in Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

and Douala

Douala

Douala is the largest city in Cameroon and the capital of Cameroon's Littoral Province. Home to Cameroon's largest port and its major international airport, Douala International Airport, it is the commercial capital of the country...

in early 20th century should be uncircumcised, and these cities were the probable epicenters of HIV-1 groups M and O, respectively.

The authors studied early circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

frequencies in 12 cities of Central and West Africa, to test if this variable correlated with HIV emergence. This correlation

Correlation

In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....

was strong for HIV-2: among 6 West African cities that could have received immigrants infected with SIVsmm, the two cities from the Ivory Coast studied (Abidjan

Abidjan

Abidjan is the economic and former official capital of Côte d'Ivoire, while the current capital is Yamoussoukro. it was the largest city in the nation and the third-largest French-speaking city in the world, after Paris, and Kinshasa but before Montreal...

and Bouaké

Bouaké

Bouaké is the second largest city in Côte d'Ivoire, with a population of 775,300 . It is the main urban settlement of the Bouaké Department with a population exceeding 1.2 million, in the Vallée du Bandama Region...

) had much higher frequency of uncircumcised men (60—85%) than the others, and epidemic HIV-2 groups emerged initially in this country only. This correlation was less clear for HIV-1 in Central Africa.

Computer simulations of HIV emergence

Sousa et al. then built computer simulation

Computer simulation

A computer simulation, a computer model, or a computational model is a computer program, or network of computers, that attempts to simulate an abstract model of a particular system...

s to test if an 'ill-adapted SIV' (meaning a simian immunodeficiency virus

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

already infecting a human but incapable of transmission beyond the short acute infection

Acute HIV infection

period) could spread in colonial cities. The simulations used parameter

Parameter

Parameter from Ancient Greek παρά also “para” meaning “beside, subsidiary” and μέτρον also “metron” meaning “measure”, can be interpreted in mathematics, logic, linguistics, environmental science and other disciplines....

s of sexual transmission obtained from the current HIV literature. They modelled people's 'sexual links', with different levels of sexual partner change among different categories of people (prostitutes, single women with several partners a year, married women, and men), according to data obtained from modern studies of sexual promiscuity in African cities. The simulations let the parameters (city size, proportion of people married, GUD frequency, male circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

frequency, and transmission parameters) vary, and explored several scenarios. Each scenario was run 1,000 times, to test the probability of SIV generating long chains of sexual transmission. The authors postulated that such long chains of sexual transmission were necessary for the SIV strain to adapt better to humans, becoming a HIV capable of further epidemic emergence.

The main result was that genital ulcer

Genital ulcer

frequency was by far the most decisive factor. For the GUD levels prevailing in Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

, in early 20th century, long chains of SIV transmission had a high probability. For the lower GUD levels existing in the same city in the late 1950s (see above), they were much less likely. And without GUD (a situation typical of villages in forested equatorial Africa before colonialism

Colonialism

) SIV could not spread at all. City size was not an important factor. The authors propose that these findings explain the temporal patterns of HIV emergence: no HIV emerging in tens of thousands of years of human slaughtering of ape

Ape

s and monkey

Monkey

s, several HIV groups emerging in the nascent, GUD-riddled, colonial cities, and no epidemically successful HIV group emerging in mid-20th century, when GUD was more controlled, and cities were much bigger.

Male circumcision

Circumcision

Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

had little to moderate effect in their simulations, but given the geographical correlation

Correlation

found, the authors propose that it could have had an indirect role, either by increasing genital ulcer disease itself (it is known that syphilis

Syphilis

, chancroid

Chancroid

Chancroid is a sexually transmitted infection characterized by painful sores on the genitalia...

, and several other GUDs have higher incidences in uncircumcised men), or by permitting further spread of the HIV strain, after the first chains of sexual transmission permitted adaptation

Adaptation

to the human organism.

One of the main advantages of this theory is stressed by the authors: "It [the theory] also offers a conceptual simplicity because it proposes as causal factors for SIV adaptation to humans and initial spread the very same factors that most promote the continued spread of HIV nowadays: promiscuous sex, particularly involving sex workers, GUD, and possibly lack of circumcision."

Iatrogenic and other theories

Iatrogenic theories propose that medical interventions were responsible for HIV origins. By proposing factors that only appeared in Central and West Africa after the late 19th century, they seek to explain why all HIV groups also started after that.

The theories centered on the role of parenteral

Parenteral

Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...

risks, such as unsterile injections, transfusion

Blood transfusion

Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

s, or smallpox

Smallpox

vaccinations are accepted as plausible by most scientists of the field, and were already reviewed above.

Pathogenicity of SIV in non-human primates

In most non-human primate species, natural SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

infection does not cause a fatal disease (but see below). Comparison of the gene sequence of SIV with HIV should therefore give us information about the factors necessary to cause disease in humans. The factors that determine the virulence of HIV as compared to most SIVs are only now being elucidated. Non-human SIVs contain a nef gene that down-regulates CD3, CD4

CD4

CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

, and MHC class I

MHC class I

MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

expression; most non-human SIVs therefore do not induce immunodeficiency; the HIV-1 nef gene however has lost its ability to down-regulate CD3, which results in the immune activation and apoptosis that is characteristic of chronic HIV infection.

In addition, a long term survey of chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s naturally infected with SIVcpz in Gombe, Tanzania

Tanzania

, found that, contrary to the previous paradigm

Paradigm

The word paradigm has been used in science to describe distinct concepts. It comes from Greek "παράδειγμα" , "pattern, example, sample" from the verb "παραδείκνυμι" , "exhibit, represent, expose" and that from "παρά" , "beside, beyond" + "δείκνυμι" , "to show, to point out".The original Greek...

, chimpanzees with SIVcpz infection, not only had increased mortality, but also suffered from an AIDS-like illness. SIV pathogenicity in wild animals could exist in other chimpanzee subspecies and other primate species as well, and stay unrecognized by lack of relevant long term studies.

1955–1957: David Carr

The oldest putative case of the then-unknown syndrome was thought to be a 1959 observation, when David Carr, a 25-year-old British printer

Printer (publisher)

In publishing, printers are both companies providing printing services and individuals who directly operate printing presses. With the invention of the moveable type printing press by Johannes Gutenberg around 1450, printing—and printers—proliferated throughout Europe.Today, printers are found...

who had served in the Royal Navy

Royal Navy

The Royal Navy is the naval warfare service branch of the British Armed Forces. Founded in the 16th century, it is the oldest service branch and is known as the Senior Service...

between 1955 and 1957 (but apparently not in Africa) sought help at the Royal Infirmary of Manchester

Manchester

Manchester is a city and metropolitan borough in Greater Manchester, England. According to the Office for National Statistics, the 2010 mid-year population estimate for Manchester was 498,800. Manchester lies within one of the UK's largest metropolitan areas, the metropolitan county of Greater...

, England. He was reported to be suffering from puzzling symptoms, among them purplish skin lesion

Kaposi's sarcoma

Kaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...

s, for nearly two years. His condition deteriorated during Christmas 1958 when he started suffering from shortness of breath, extreme fatigue

Fatigue (physical)

Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...

, rapid weight loss

Weight loss

Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, night sweats, and high fever. Doctors thought he might be suffering from tuberculosis

Tuberculosis

and even though they found no evidence of bacterial infection, they treated him for tuberculosis as a safety measure, but without success. Carr continued to weaken and he died shortly after in August 1959. His autopsy revealed evidence of two unusual infections, cytomegalovirus

Cytomegalovirus

Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

and Pneumocystis carinii pneumonia

Pneumocystis pneumonia

Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...

(PCP, later renamed Pneumocystis pneumonia

Pneumocystis pneumonia

Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...

when redetermined to be P. jirovecii), very rare at the time but now commonly associated with AIDS patients. His case puzzled his doctors, who preserved tissue samples from him and for years retained some interest in solving the mystery.

Sir Robert Platt, then president of the Royal College of Physicians

Royal College of Physicians

The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...

, wrote in the printer's hospital chart that he wondered "If we are in for a new wave of virus disease now that the bacterial illnesses are so nearly conquered". It was only 31 years later, after the AIDS pandemic

AIDS pandemic

The acquired immune deficiency syndrome pandemic is a widespread disease caused by the human immunodeficiency virus .Since AIDS was first recognized in 1981, it has led to the deaths of more than 25 million people, making it one of the most destructive diseases in recorded history.Despite recent...

had become well-known and widespread, that they decided to perform HIV tests on Carr's preserved tissues, which initially returned a positive result. The British medical journal The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

reported Carr's case in its July 7, 1990 issue, but later retracted its claim of positive identification in the January 20, 1996 issue, reporting that the tissue sample had become contaminated in the laboratory.

1959: Congolese man

One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa

Kinshasa

Kinshasa is the capital and largest city of the Democratic Republic of the Congo. The city is located on the Congo River....

, Democratic Republic of the Congo). However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.

1960: Congolese woman

A second early documented HIV-1 infection was discovered in a preserved lymph node

Lymph node

A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.

1969: Robert R.

In 1969, a 15-year-old African-American male known to medicine as Robert R.

Robert R.

Robert Rayford , sometimes identified as Robert R. due to his age, was an American teenager from Missouri who was the earliest confirmed victim of HIV/AIDS in North America. His death at the age of 16 baffled doctors at the time...

died at the St. Louis

St. Louis, Missouri

St. Louis is an independent city on the eastern border of Missouri, United States. With a population of 319,294, it was the 58th-largest U.S. city at the 2010 U.S. Census. The Greater St...

City Hospital from aggressive Kaposi's sarcoma

Kaposi's sarcoma

. AIDS was suspected as early as 1984, and in 1987, researchers at Tulane University School of Medicine

Tulane University School of Medicine

The Tulane University School of Medicine is located in New Orleans, Louisiana, USA and is a part of Tulane University. The school is located in the Medical District of the New Orleans Central Business District.-History:...

confirmed this, finding HIV-1 in his preserved blood and tissues. The doctors who worked on his case at the time suspected he was a prostitute, though the patient did not discuss his sexual history with them in detail.

1969: Arvid Noe

In 1976, a Norwegian

Norway

Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...

sailor, with the alias name Arvid Noe

Arvid Noe

Arvid Noe is the alias of a Norwegian sailor who is the first person known to have contracted HIV and died from AIDS outside of the United States. He is the second person confirmed to have died from AIDS, after the teenager known as Robert R., from St. Louis, Missouri, in 1969.-Biography:Noe...

, his wife, and his nine-year-old daughter died of AIDS. The sailor had first presented symptoms in 1969, eight years after he first spent time in ports along the West African coastline. A gonorrhea

Gonorrhea

Gonorrhea is a common sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. The usual symptoms in men are burning with urination and penile discharge. Women, on the other hand, are asymptomatic half the time or have vaginal discharge and pelvic pain...

infection during his first African voyage shows he was sexually active at this time. Tissue samples from the sailor and his wife were tested in 1988 and found to contain HIV-1 (Group O).

Spread to the western hemisphere

HIV-1 strains are thought to have arrived in the United States from Haiti in the late 1960s or early 1970s. HIV-1 is believed to have arrived in Haiti from central Africa, possibly through professional contacts with the Democratic Republic of the Congo

Democratic Republic of the Congo

The Democratic Republic of the Congo is a state located in Central Africa. It is the second largest country in Africa by area and the eleventh largest in the world...

. The current consensus is that HIV was introduced to Haiti by an unknown individual or individuals who contracted it while working in the Democratic Republic of the Congo circa 1966, or from another person who worked there during that time. A mini-epidemic followed, and, circa 1969, yet another unknown individual brought HIV from Haiti to the United States. The vast majority of cases of AIDS outside sub-Saharan Africa can be traced back to that single patient (although numerous unrelated incidents of AIDS among Haitian immigrants to the U.S. were recorded in the early 1980s, and, as evidenced by the case of Robert R.

Robert R.

, isolated incidents of this infection may have been occurring as early as 1966.) The virus eventually entered male gay communities in large United States cities, where a combination of sexual promiscuity (with individuals reportedly averaging over 11 unprotected sexual partners per year) and relatively high transmission rates associated with anal intercourse allowed it spread explosively enough to finally be noticed.

Because of the long incubation period of HIV (up to a decade or longer) before symptoms of AIDS appear, and because of the initially low incidence, AIDS was not noticed at first. By the time the first reported cases of AIDS were found in large United States cities, the prevalence of HIV infection in some communities had passed 5%. Worldwide, HIV infection has spread from urban to rural areas, and has appeared in regions such as China and India

India

India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

Canadian flight attendant theory

A Canadian airline steward named Gaëtan Dugas

Gaëtan Dugas

Gaëtan Dugas was a Canadian who worked for Air Canada as a flight attendant. Dugas became notorious as the alleged patient zero for AIDS, though he is now more accurately regarded as one of many highly sexually active men who spread AIDS widely before the disease was identified.-Patient Zero...

was referred to as "Patient 0" in an early AIDS study by Dr. William Darrow

William Darrow

William "Bill" Darrow is a Professor of Public Health at Florida International University in Miami, Florida.Before accepting a position at FIU in August, 1994, Darrow served as Chief of the Behavioral and Prevention Research Branch, Division of STD/HIV Prevention, at the National Center for...

of the Centers for Disease Control. Because of this, many people had considered Dugas to be responsible for bringing HIV to North America. This is inaccurate however, as HIV had spread long before Dugas began his career. This rumor may have started with Randy Shilts

Randy Shilts

Randy Shilts was a pioneering gay American journalist and author. He worked as a freelance reporter for both The Advocate and the San Francisco Chronicle, as well as for San Francisco Bay Area television stations....

' 1987 book And the Band Played On
And the Band Played On
And the Band Played On: Politics, People, and the AIDS Epidemic is a nonfiction book written by San Francisco Chronicle journalist Randy Shilts, published in 1987...

(and the movie based on it, in which Dugas is referred to as AIDS' Patient Zero), but neither the book nor the movie state that he had been the first to bring the virus to North America. He was called "Patient Zero" because at least 40 of the 248 people known to be infected by AIDS in 1983 had had sex with him, or with someone who had sexual intercourse with him.

1981–2: From GRID to AIDS

The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention

Centers for Disease Control and Prevention

The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

in its Morbidity and Mortality Weekly Report
Morbidity and Mortality Weekly Report
The Morbidity and Mortality Weekly Report is a weekly epidemiological digest for the United States published by the Centers for Disease Control and Prevention...

newsletter reported unusual clusters of Pneumocystis pneumonia (PCP) caused by a form of Pneumocystis carinii (now recognized as a distinct species Pneumocystis jirovecii) in five homosexual men in Los Angeles.

Over the next 18 months, more PCP clusters were discovered among otherwise healthy men in cities throughout the country, along with other opportunistic diseases (such as Kaposi's sarcoma

Kaposi's sarcoma

and persistent, generalized lymphadenopathy), common in immunosuppressed patients.

In June 1982, a report of a group of cases amongst gay men in Southern California

Southern California

Southern California is a megaregion, or megapolitan area, in the southern area of the U.S. state of California. Large urban areas include Greater Los Angeles and Greater San Diego. The urban area stretches along the coast from Ventura through the Southland and Inland Empire to San Diego...

suggested that a sexually transmitted

Sexually transmitted disease

infectious agent

Infectious disease

Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

might be the etiological

Etiology

Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

agent, and the syndrome was initially termed "GRID", or gay-related immune deficiency

Gay-related immune deficiency

Gay-related immune deficiency was the 1982 name first proposed to describe what is now known as AIDS, after public health scientists noticed clusters of Kaposi's sarcoma and Pneumocystis pneumonia among gay males in Southern California and New York City.During the early history of AIDS, when it was...

.

Health authorities soon realized that nearly half of the people identified with the syndrome were not homosexual men. The same opportunistic infections were also reported among hemophiliacs, heterosexual intravenous drug

Drug injection

In substance dependence and recreational drug use, drug injection is a method of introducing a drug into the body with a hollow needle and a syringe which is pierced through the skin into the body...

users, and Haitian immigrants—leading some researchers to call it the "4H" disease.

By August 1982, the disease was being referred to by its new CDC-coined name: Acquired Immune Deficiency Syndrome (AIDS).

May 1983: LAV

In May 1983, doctors from Dr. Luc Montagnier

Luc Montagnier

Luc Antoine Montagnier is a French virologist and joint recipient with Françoise Barré-Sinoussi and Harald zur Hausen of the 2008 Nobel Prize in Physiology or Medicine, for his discovery of the human immunodeficiency virus...

's team at the Pasteur Institute

Pasteur Institute

The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...

in France reported that they had isolated a new retrovirus

Retrovirus

A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...

from lymphoid ganglions

Lymph node

that they believed was the cause of AIDS. The virus was later named lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers for Disease Control, which was later passed to the National Cancer Institute

National Cancer Institute

The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

(NCI).

May 1984: HTLV-III

In May 1984 a team led by Robert Gallo

Robert Gallo

Robert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the Human Immunodeficiency Virus , the infectious agent responsible for the Acquired Immune Deficiency Syndrome , and he has been a major contributor to subsequent HIV research.Gallo is the...

of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III).

Jan 1985: both found to be the same

In January 1985 a number of more detailed reports were published concerning LAV and HTLV-III, and by March it was clear that the viruses were the same, were from the same source, and were the etiological agent of AIDS.

May 1986: the name HIV

In May 1986, the International Committee on Taxonomy of Viruses

International Committee on Taxonomy of Viruses

The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to...

ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used.

Genetic studies

According to a 2008 Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences

The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences...

study, a team led by Robert Shafer at Stanford University School of Medicine

Stanford University School of Medicine

Stanford University School of Medicine is a leading medical school located at Stanford University Medical Center in Stanford, California. Originally based in San Francisco, California as Cooper Medical College, it is the oldest continuously running medical school in the western United States...

has discovered that the Gray Mouse Lemur

Gray Mouse Lemur

The gray mouse lemur , or lesser mouse lemur, is a small lemur, a type of strepsirrhine primate, found only on the island of Madagascar. Weighing , it is the largest of the mouse lemurs , a group which include the smallest primates in the world...

has an endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

lentivirus

Lentivirus

Lentivirus is a genus of slow viruses of the Retroviridae family, characterized by a long incubation period...

(the genus to which HIV belongs) in its genetic makeup. This suggests that lentiviruses have existed for at least 14 million years, much longer than the currently known existence of HIV. In addition, the time frame falls into place when Madagascar was still yet connected to what is now the African continent; the said lemurs later developed immunity to the virus strain and survived an era

Middle Miocene disruption

The term Middle Miocene disruption, alternatively the Middle Miocene extinction or Middle Miocene extinction peak, refers to a wave of extinctions of terrestrial and aquatic life forms that occurred around the middle of the Miocene Epoch, c...

when the lentivirus was widespread among other mammalia. The study is being hailed as crucial, because it fills the blanks in the origin of the virus, as well as in its evolution, and may be important in the development of new antiviral drugs.

In 2010, researchers reported that SIV

Simian immunodeficiency virus

Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

had infected monkeys in Bioko

Bioko

Bioko is an island 32 km off the west coast of Africa, specifically Cameroon, in the Gulf of Guinea. It is the northernmost part of Equatorial Guinea with a population of 124,000 and an area of . It is volcanic with its highest peak the Pico Basile at .-Geography:Bioko has a total area of...

for at least 32,000 years. Previously it was thought that SIV infection in monkeys had happened over the past few hundred years. Scientists estimated that it would take a similar amount of time before humans adapted naturally to HIV infection in the way monkeys in Africa have adapted to SIV and not suffer any harm from the infection.

Discredited theories

Several alternative hypotheses for the origin of AIDS have been proposed. AIDS denialism argues that HIV or AIDS does not exist or that AIDS is not caused by HIV; some of its proponents believe that AIDS is caused by lifestyle, including sexuality or drug use. Some conspiracy theories allege that HIV was created in a bioweapons laboratory, perhaps as an agent of genocide

Genocide

Genocide is defined as "the deliberate and systematic destruction, in whole or in part, of an ethnic, racial, religious, or national group", though what constitutes enough of a "part" to qualify as genocide has been subject to much debate by legal scholars...

or an accident. These hypotheses have been rejected by scientific consensus

Scientific consensus

Scientific consensus is the collective judgment, position, and opinion of the community of scientists in a particular field of study. Consensus implies general agreement, though not necessarily unanimity. Scientific consensus is not by itself a scientific argument, and it is not part of the...