AIDS is caused by the Human immunodeficiency virus (HIV), which originated in non-human primates in Sub-Saharan Africa 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.[1] The pandemic strain of HIV-1 is closely related to a virus found in the chimpanzees of the subspecies Pan troglodytes troglodytes, which lives 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][2]
Most 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.
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 to the SIV that infects Western lowland gorillas (Gorilla gorilla gorilla), called SIVgor.[3][4][5][6][7][8] 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.[3] Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of the same country.[6] 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.[5] 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.[3] 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, but rather farther south in the Democratic Republic of the Congo, more probably in its capital city, Kinshasa.[3][9][10][11]
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 datation 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.[12][13][14] 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).[15][16]
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".[15] The results of a 2008 phylogenetics study support the later work and indicate that HIV evolves "fairly reliably".[15][17]
Similar researches were 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 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.[2]
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.[2][11][18]
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).[19] [20]
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"[7] 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.[21] 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 practiced, and 17.1% in the most exposed people of these villages.[22] 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 virions capable of adjusting so that they could infect and reproduce in the T cells of a human host.
Zoonosis (transfer of a pathogen from non-human animals to humans) and subsequent spread of the pathogen between humans, requires the following conditions:
It is clear that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and SIVsmm viruses,[2][5][6][7][9][18] and that bushmeat practice provides the most plausible venue for cross-species transfer to humans.[7][9][22] 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,[10] and the resulting human SIV infections being common.[22]
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).[23]
The discovery of the main HIV / SIV phylogenetic relationships permits to explain broadly HIV biogeography: the early epicenters 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 epicenters 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 only one of 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 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.
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 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 odds of continued spread.
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".[7] 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[24] and many remained unmarried or divorced during long periods,[10][25] this being very rare in African traditional societies.[26] 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.[15]
Clearly, there is a constellation of factors associated with the social changes prompted by colonialism 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.
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.[27] The workers in plantations, construction projects, and other colonial enterprises were supplied with bushmeat, this contributing to increase this activity, and then exposures to SIV. Several historical sources support the view that bushmeat hunting indeed increased, both because of the necessity to supply workers and because projectile-firing weapons proliferated.[27][28][29]
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).[27] 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.[30]
The authors predicted that HIV-1 originated in the area of French Equatorial Africa, 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.[12][13][15][31] 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 which 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, 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).
This theory was later dubbed 'Heart of Darkness' by Jim Moore,[32] alluding to the book of the same title written by Joseph Conrad, the main focus of which is colonial abuses in 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.[16][18][33][34] Although both Chitnis et al.[27] and Sharp et al.[7] 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.[18][33]
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.[18] 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.[18]
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.[22] 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.[18][33]
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.[18]
The molecular datation studies place the initial spread of the epidemic HIV groups before that time (see above).[12][13][15][19][20][31] 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.[18]
David Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis (sleeping sickness) in Central Africa were responsible for the emergence of HIV-1.[35] Unlike Marx et al.,[18] 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.[35]
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.[12][13][15][31] 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.[35]
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.[36]
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."[36] 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 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.[37]
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).[10] 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.[10][38]
Sousa et al. use molecular datation 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 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' MRCAs (described above) mean that all HIV groups likely crossed to humans in late 19th—early 20th century.[10]
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, Kinshasa (which is the probable epicenter 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.[10]
Therefore, the peak GUD incidences in cities[10] have a good temporal coincidence with the period when all main HIV groups crossed to humans and started to spread.[10][12][13][15][19][20][31] 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).[10] Thus, this theory also potentially explains why HIV emerged only after late 19th century.
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.[38] 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.[10] 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 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 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).[10][26] About 15—30% of men in Kinshasa and Douala in early 20th century should be uncircumcised, and these cities were the probable epicenters of HIV-1 groups M and O, respectively.[10]
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.[10]
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 a 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 Kinshasa, 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) 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."[10]
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,[18][27][35][36] or smallpox vaccinations[27] are accepted as plausible by most scientists of the field, and were already reviewed above.
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.[39]
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, not only had increased mortality, but also suffered from an AIDS-like illness.[40] 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.
The oldest putative case of the then-unknown syndrome was thought to be in 1959, when David Carr, a 25-year-old British printer who was born in Reddish, Stockport and had served in the Royal Navy between 1955 and 1957 (but apparently not in Africa), sought help at the Royal Infirmary of Manchester. He was reported to be suffering from puzzling symptoms, among them purplish skin lesions, for nearly two years. His condition deteriorated during Christmas 1958, when he started suffering from shortness of breath, extreme fatigue, rapid weight loss, night sweats, and high fever. Doctors thought he might be suffering from 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 and Pneumocystis carinii pneumonia (PCP, later renamed Pneumocystis pneumonia 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 his tissue samples and retained some interest in solving the mystery for years.
Sir Robert Platt, then president of the Royal College of Physicians, 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 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 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.[41][42][43]
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, Democratic Republic of the Congo).[44] However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.[44]
A second early documented HIV-1 infection was discovered in a preserved lymph node biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.[15]
In 1969, a 15-year-old African-American male known to medicine as Robert R. died at the St. Louis City Hospital from aggressive Kaposi's sarcoma. AIDS was suspected as early as 1984, and in 1987, researchers at Tulane University School of Medicine 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.[45][46][47][48][49]
In 1976, a Norwegian sailor, with the alias name Arvid 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 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).[50][51][52]
HIV-1 strains are thought to have arrived in the United States from Haiti in the late 1960s or early 1970s.[53][54] HIV-1 is believed to have arrived in Haiti from central Africa, possibly through professional contacts with the Democratic Republic of the Congo.[55] 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.[56] 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[53] (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., 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[57]) and relatively high transmission rates associated with anal intercourse[58] allowed it spread explosively enough to finally be noticed.[53]
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%.[59] Worldwide, HIV infection has spread from urban to rural areas, and has appeared in regions such as China and India.
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 inaccurate 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 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.
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.[60]
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[61] and persistent, generalized lymphadenopathy[62]), 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,[63] and the syndrome was initially termed "GRID", or gay-related immune deficiency.[64]
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,[65] heterosexual intravenous drug users, and Haitian immigrants—leading some researchers to call it the "4H" disease.[66][67]
By August 1982, the disease was being referred to by its new CDC-coined name: Acquired Immune Deficiency Syndrome (AIDS).[68]
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.[69] 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).[69][70]
In May 1984 a team led by Robert Gallo of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III).[71]
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.[72][73]
In May 1986, the International Committee on Taxonomy of Viruses ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used.[74]
According to a 2008 Proceedings of the National Academy of Sciences study, 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.[75][76]
In 2010, researchers reported that SIV had infected monkeys in Bioko for at least 32,000 years. Previously it was thought that SIV infection in monkeys had happened over the past few hundred years.[77] 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.[78]
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 or an accident. These hypotheses have been rejected by scientific consensus.
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