History of HIV/AIDS
AIDS is caused by the human immunodeficiency virus (HIV), which originated in non-human primates in Central and West Africa. While various sub-groups of the virus acquired human infectivity at different times, the global pandemic had its origins in the emergence of one specific strain – HIV-1 subgroup M – in Léopoldville in the Belgian Congo (now Kinshasa in the Democratic Republic of the Congo) in the 1920s.
Two types of HIV exist: 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 chimpanzees of the subspecies Pan troglodytes troglodytes, which live in the forests of the Central African nations of Cameroon, Equatorial Guinea, Gabon, Republic of Congo (or Congo-Brazzaville), and Central African Republic. HIV-2 is less transmittable and is largely confined to West Africa, along with its closest relative, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey inhabiting southern Senegal, Guinea-Bissau, Guinea, Sierra Leone, Liberia, and western Ivory Coast.
- 1 Transmission from non-humans to humans
- 2 Emergence
- 2.1 Unresolved questions about HIV origins and emergence
- 2.2 Origin and epidemic emergence
- 2.2.1 Social changes and urbanization
- 2.2.2 Heart of Darkness
- 2.2.3 Unsterile injections
- 2.2.4 Genital ulcer diseases and sexual promiscuity
- 2.2.5 Iatrogenic and other theories
- 3 Pathogenicity of SIV in non-human primates
- 4 History of spread
- 5 Identification of the virus
- 6 Classification
- 7 Genetic studies
- 8 Discredited hypotheses
- 9 See also
- 10 Notes
Transmission from non-humans to humans
The majority of HIV researchers agree that HIV evolved at some point from the closely related Simian immunodeficiency virus (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). Research in this area is conducted using molecular phylogenetics, comparing viral genomic sequences to determine relatedness.
HIV-1 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 populations of West Central African forests. Particularly, each of the known HIV-1 strains is either closely related to the SIV that infects the chimpanzee subspecies Pan troglodytes troglodytes (SIVcpz) or closely related to the SIV that infects Western lowland gorillas (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 populations living in Cameroon. Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of Cameroon. Finally, the primate ancestor of HIV-1 group O, a strain infecting tens of thousands of people mostly from Cameroon but also from neighboring countries, is still uncertain, but there is evidence that it is either SIVcpz or SIVgor.However, phylogenetic and DNA research has found that the strain HIV-1 group O is more closely related to SIVgor. The pandemic HIV-1 group M is most closely related to the SIVcpz collected from the southeastern rain forests of Cameroon (modern East Province) near the Sangha River. 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 center was probably not in Cameroon, but rather farther south in the Democratic Republic of the Congo, more probably in its capital city, Kinshasa (formerly Léopoldville).
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 occurred is not known. Some molecular dating studies suggest that HIV-1 group M had its most recent common ancestor (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, 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 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". Further research was hindered due to the primates being critically endangered. Sample analyses resulted in little data due to the rarity of experimental material. The researchers, however, were able to hypothesize a phylogeny from the gathered data. They were also able to use the molecular clock of a specific strain of HIV to determine the initial date of transmission, which is predicted to be around 1915-1931. 
HIV-2 from sooty mangabeys to humans
Similar research has been undertaken with SIV strains collected from several wild sooty mangabey (Cercocebus atys atys) (SIVsmm) communities of the West African nations of Sierra Leone, Liberia, and Ivory Coast. The resulting phylogenetic analyses show that the viruses most closely related to the two strains of HIV-2 that 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 mangabeys to humans. Groups C and D have been found in two people from Liberia, groups E and F have been discovered in two people from 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.
See also this article about HIV types, groups, and subtypes.
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 or monkey to a human when a hunter or bushmeat 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.Prior to WWII, some Sub-Saharan Africans were forced out of the rural areas because of the European demand for resources. Since rural Africans were not keen to pursue agricultural practices in the jungle, they turned to non-domesticated meat as their primary source of protein. This over exposure to bushmeat and malpractice of butchery increased blood-to-blood contact, which then increased the probability of transmission. A recent serological survey showed that human infections by SIV are not rare in Central Africa: the percentage of people showing seroreactivity to antigens — evidence of current or past SIV infection — was 2.3% among the general population of Cameroon, 7.8% in villages where bushmeat is hunted or used, 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 handler from the ape/monkey is still a matter of debate, although natural selection would favor any viruses capable of adjusting so that they could infect and reproduce in the T cells of a human host.
A study published in 2009 also discussed that bushmeat in other parts of the world, such as Argentina, may be a possible location for where the disease originated. HIV-1C, a subtype of HIV, was theorized to have its origins circulating among South America.  The consumption of bushmeat is also the most probable cause for the emergence of HIV-1C in South America. However, the types of apes, shown to carry the SIV virus, are different in South America. The primary point of entry, according to researchers, is somewhere in the jungles of Argentina or Brazil.  An SIV strain, closely related to HIV, was interspersed within a certain clade of primates. This suggests that the zoonotic transmission of the virus may have happened in this area.  Continual emigration between countries escalated the transmission of the virus. Other scientists believe that the HIV-1C strain circulated in South America at around the same time that the HIV-1C strain was introduced in Africa.  Very little research has been done on this theory because it is fairly young. However, promising evidence indicates that there may be some validity to this hypothesis.
Unresolved questions about HIV origins and emergence
The discovery of the main HIV / SIV phylogenetic relationships permits explaining broadly HIV biogeography: the early centers of the HIV-1 groups were in Central Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses (chimpanzees and gorillas) exist; similarly, the HIV-2 groups had their centers in West Africa, where sooty mangabeys, 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 one of only six countries harboring the sooty mangabey. It is also unclear why the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes schweinfurthii (inhabiting the Democratic Republic of Congo, Central African Republic, Rwanda, Burundi, Uganda, and Tanzania) did not spawn an epidemic HIV-1 strain to humans, while the Democratic Republic of Congo was the main center of HIV-1 group M, a virus descended from SIVcpz strains of a subspecies (Pan troglodytes troglodytes) that does not exist in this country. 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 practices being very widespread in Central and West Africa, and the resulting human SIV infections being common.
It also remains 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).
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 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 known 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 (thus enhancing its between-humans transmissibility), or to cause an initial burst of transmissions crossing an epidemiological threshold, and therefore increasing the probability of continued spread.
Genetic studies of the virus suggested in 2008 that the most recent common ancestor of the HIV-1 M group dates back to the Belgian Congo city of Léopoldville (modern Kinshasa), circa 1910. Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of sexual promiscuity, the spread of prostitution, and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.
In 2014, a study conducted by scientists from the University of Oxford and the University of Leuven, in Belgium, revealed that because approximately one million people every year would flow through the prominent city of Kinshasa, which served as the origin of the first known HIV cases in the 1920s, passengers riding on the region's Belgian railway trains were able to spread the virus to larger areas. The study also attributed a roaring sex trade, rapid population growth and unsterilised needles used in health clinics as other factors which contributed to the emergence of the Africa HIV epidemic.
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 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 probably played a role in the epidemic emergence of HIV, since the phylogenetic dating 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.
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 practices associated with colonialism, particularly in French Equatorial Africa. The workers in plantations, construction projects, and other colonial enterprises were supplied with bushmeat, which would have contributed to an increase in hunting and, it follows, a higher incidence of human exposure to SIV. Several historical sources support the view that bushmeat hunting indeed increased, both because of the necessity to supply workers and because firearms became more widely available.
The colonial authorities also gave many vaccinations against smallpox, 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 risks and the prostitution associated with forced labor camps could have caused serial transmission (or serial passage) 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 of workers, therefore prolonging the primary acute infection 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 proposed that HIV-1 originated in the area of French Equatorial Africa 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 apes living to the west of the Ubangi River, either in countries that belonged to the French Equatorial Africa federation of colonies, in Equatorial Guinea (then a Spanish colony), or in Cameroon (which was a German colony between 1884 and 1916, and 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).
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 (after a 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 (or serial transmission): an adventitious virus (or other pathogen) can increase its biological adaptation to a new host species if it is rapidly transmitted between hosts, while each host is still in the acute infection period. This process favors the accumulation of adaptive mutations more rapidly, therefore increasing the odds that a better adapted viral variant will appear in the host before the immune system suppresses the virus. Such better adapted variant could then survive in the human host for longer than the short acute infection period, in high numbers (high viral load), 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 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 loads in the human organism, adventitious SIV infecting humans seldom does so: people with SIV antibodies often have very low or even undetectable SIV viral load. This suggests that both HIV-1 and HIV-2 are adapted to humans, and 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 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 antibiotics 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 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 era.
The molecular dating 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 assumption, may not have accounted for the effects of natural selection in the viruses, and the serial passage process alone would be associated with strong natural selection.
The injection campaigns against sleeping sickness
David Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis (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 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.
Other early injection campaigns
Jacques Pépin and Annie-Claude Labbé reviewed the colonial health reports of Cameroon and French Equatorial Africa for the period 1921–59, calculating the incidences of the diseases requiring intravenous injections. They concluded that trypanosomiasis, leprosy, yaws, and syphilis were responsible for most intravenous injections. Schistosomiasis, tuberculosis, and vaccinations against smallpox represented lower parenteral 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 virus in southern Cameroon and forested areas of French Equatorial Africa (around 40–50%) can be better explained by the unsterile injections used to treat yaws, because this disease was much more prevalent than syphilis, trypanosomiasis, and leprosy in these areas. They suggested that all these parenteral risks caused, not only the massive spread of Hepatitis C but also the spread of other pathogens, 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 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 using improperly sterilized syringe and needles playing a key role in enabling a future epidemic. Pépin concludes that AIDS spread silently in Africa for decades, fueled by urbanization and prostitution since the initial cross-species infection. Pépin also claims that the virus was brought to the Americas by a Haitian teacher returning home from Zaire in the 1960s. Sex tourism and contaminated blood transfusion centers ultimately propelled AIDS to public consciousness in the 1980s and a worldwide pandemic.
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 ulcers, caused by genital ulcer diseases (GUD). GUD are simply sexually transmitted diseases that cause genital ulcers; examples are syphilis, chancroid, lymphogranuloma venereum, 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 cells expressing the CCR5 co-receptor, the main cell targets of HIV.
The probable time interval of cross-species transfer
Sousa et al. use molecular dating techniques to estimate the time when each HIV group split from its closest SIV lineage. Each HIV group necessarily crossed to humans between this time and the time when it started to spread (the time of the MRCA), because after the MRCA certainly all lineages were already in humans, and before the split with the closest simian strain, the lineage was in a simian. HIV-1 groups M and O split from their closest SIVs around 1931 and 1915, respectively. This information, together with the datations of the HIV groups' MRCAs, mean that all HIV groups likely crossed to humans in the 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 chimpanzees, gorillas and sooty mangabeys, 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 favoured prostitution, which in its turn caused an explosion of GUD (especially syphilis and chancroid). After the mid-1930s, people's movements were more tightly controlled, and mass surveys and treatments (of arsenicals 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 antibiotics, so that, by the late 1950s, Léopoldville (which is the probable center of HIV-1 group M) had a very low GUD incidence. Similar processes happened in the cities of 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 and the other GUDs were, like injections, absent from the densely forested areas of Central and West Africa before organized colonialism socially disrupted these areas (starting in the 1880s). Thus, this theory also potentially explains why HIV emerged only after the late 19th century.
Female genital mutilation
Uli Linke has argued that the practice of female genital mutilation is responsible for the high incidence of AIDS in Africa, since intercourse with a circumcised female is conducive to exchange of blood.
Male circumcision distribution and HIV origins
Male circumcision may reduce the probability of HIV acquisition by men (see article Circumcision and HIV). Leaving aside blood transfusions, 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 literature for patterns of male circumcision and hunting of apes and monkeys for bushmeat, focusing on the period 1880–1960, and on most of the 318 ethnic groups 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.
Sousa et al. charts reveal that male circumcision frequencies were much lower in several cities of western and central Africa in the early 20th century than they are currently. The reason is that many ethnic groups not performing circumcision by that time gradually adopted it, to imitate other ethnic groups and enhance the social acceptance of their boys (colonialism produced massive intermixing between African ethnic groups). About 15–30% of men in Léopoldville and Douala in the early 20th century should be uncircumcised, and these cities were the probable centers of HIV-1 groups M and O, respectively.
The authors studied early circumcision frequencies in 12 cities of Central and West Africa, to test if this variable correlated with HIV emergence. This correlation 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 and Bouaké) 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 simulations to test if an 'ill-adapted SIV' (meaning a simian immunodeficiency virus already infecting a human but incapable of transmission beyond the short acute infection period) could spread in colonial cities. The simulations used parameters 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 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 an HIV capable of further epidemic emergence.
The main result was that genital ulcer frequency was by far the most decisive factor. For the GUD levels prevailing in Léopoldville in the 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) 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 apes and monkeys, 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 had little to moderate effect in their simulations, but, given the geographical 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, chancroid, 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 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 risks, such as unsterile injections, transfusions, or smallpox vaccinations are accepted as plausible by most scientists of the field, and were already reviewed above.
Discredited HIV/AIDS origins theories include several iatrogenic theories, such as Edward Hooper's 1999 claim that early oral polio vaccines, contaminated with a chimpanzee virus, caused the Central African outbreak.
Pathogenicity of SIV in non-human primates
In most non-human primate species, natural SIV 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, and MHC class I 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 chimpanzees naturally infected with SIVcpz in Gombe, Tanzania found that, contrary to the previous paradigm, chimpanzees with SIVcpz infection do experience an increased mortality, and also suffer from a Human 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.
History of spread
1959: David Carr
David Carr was an apprentice printer (usually referred to, mistakenly, as a sailor; Carr had served in the Navy between 1955 and 1957) from Manchester, England who died August 31, 1959, and was for some time mistakenly reported to have died from AIDS-defining opportunistic infections (ADOIs). Following the failure of his immune system, he succumbed to pneumonia. Doctors, baffled by what he had died from, preserved 50 of his tissue samples for inspection. In 1990, the tissues were found to be HIV-positive. However, in 1992, a second test by AIDS researcher David Ho found that the strain of HIV present in the tissues was similar to those found in 1990 rather than an earlier strain (which would have mutated considerably over the course of 30 years). He concluded that the DNA samples provided actually came from a 1990 AIDS patient. Upon retesting David Carr's tissues, he found no sign of the virus.
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 Léopoldville in the Belgian Congo. However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.
1960: Congolese woman
1969: Robert Rayford
In May 1969 16-year-old African-American Robert Rayford died at the St. Louis City Hospital from Kaposi's sarcoma. In 1987 researchers at Tulane University School of Medicine detected "a virus closely related or identical to" HIV-1 in his preserved blood and tissues. The doctors who worked on his case at the time suspected he was a prostitute or the victim of sexual abuse, though the patient did not discuss his sexual history with them in detail.
1969: Arvid Noe
In 1975 and 1976, a Norwegian sailor, with the alias name Arvid Noe, his wife, and his seven-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 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).
1973: Ugandan children
From 1972 to 1973, researchers drew blood from 75 children in Uganda to serve as controls for a study of Burkitt's lymphoma. In 1985, retroactive testing of the frozen blood serum indicated that antibodies to a virus related to HIV were present in 50 of the children.
Spread to the western hemisphere
HIV-1 strains were once 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 from the Democratic Republic of the Congo. 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 Rayford, 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 to 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, HIV 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.
Canadian flight attendant theory
A Canadian airline steward named Gaëtan Dugas was referred to as "Patient 0" in an early AIDS study by Dr. William Darrow 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 not accurate, however, as HIV had spread long before Dugas began his career. This rumor may have started with Randy Shilts' 1987 book And the Band Played On (and the 1993 movie based on it, in which Dugas is referred to as AIDS' Patient Zero), but neither the book nor the movie states 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 HIV in 1983 had had sex with him, or with someone who had sexual intercourse with him.
1981: From GRID to AIDS
The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention in its Morbidity and Mortality Weekly Report 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 and persistent, generalized lymphadenopathy), common in immunosuppressed patients.
In June 1982, a report of a group of cases amongst gay men in Southern California suggested that a sexually transmitted infectious agent might be the etiological agent, and the syndrome was initially termed "GRID", or gay-related immune deficiency.
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 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).
Identification of the virus
May 1983: LAV
In May 1983, doctors from Dr. Luc Montagnier's team at the Pasteur Institute in France reported that they had isolated a new retrovirus from lymphoid ganglions 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 (NCI).
May 1984: HTLV-III
January 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
Whether Gallo or Montagnier deserve more credit for the discovery of the virus that causes AIDS has been a matter of considerable controversy. Together with his colleague Françoise Barré-Sinoussi, Montagnier was awarded one half of the 2008 Nobel Prize in Physiology or Medicine for his "discovery of human immunodeficiency virus". Harald zur Hausen also shared the prize for his discovery that human papilloma virus leads to cervical cancer, but Gallo was left out. Gallo said that it was "a disappointment" that he was not named a co-recipient. Montagnier said he was "surprised" Gallo was not recognized by the Nobel Committee: "It was important to prove that HIV was the cause of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo."
Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition.
According to a study published in the Proceedings of the National Academy of Sciences in 2008, a team led by Robert Shafer at Stanford University School of Medicine has discovered that the Gray Mouse Lemur has an endogenous lentivirus (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 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 had infected monkeys in Bioko for at least 32,000 years. Previous to this time, 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.
Other 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, and not by HIV. Some conspiracy theories allege that HIV was created in a bioweapons laboratory, perhaps as an agent of genocide or an accident. These hypotheses have been rejected by scientific consensus.
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