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AIDS is caused by a 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.
There are two types of HIV: HIV-1 and HIV-2. HIV-1 is more virulent, 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 chimpanzees of the subspecies Pan troglodytes troglodytes, which live in the forests of the Central African nations of Cameroon, Equatorial Guinea, Gabon, the Republic of the Congo (or Congo-Brazzaville), and the 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.
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. In particular, 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 rare strain found
only 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
100,000 people mostly from Cameroon but also from neighbouring
countries, was confirmed in 2006 to be 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 centre was probably not in Cameroon, but
rather further south in the Democratic Republic of the Congo (then the Belgian 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
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 estimated 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) populations 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.
Molecular dating 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).
Bushmeat practice
According
to the natural transfer theory (also called "hunter theory" or
"bushmeat theory"), in 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 animals as their primary
source of meat. 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 favour any viruses capable of
adjusting so that they could infect and reproduce in the T cells of a human host.
Emergence
Unresolved questions about HIV origins and emergence
The discovery of the main HIV / SIV phylogenetic relationships permits explaining broad HIV biogeography: the early centres 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 centres in West Africa, where sooty mangabeys,
which harbour 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 harbouring 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 centre 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 cause of cross-species transfer to humans. However, some loose ends remain.
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 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 accept the 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 non-monogamous sexual activity, 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 identified 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
Beatrice Hahn, Paul M. Sharp,
and their colleagues proposed 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 casual sexual
activity with an increased number of partners. In the nascent cities
women felt relatively liberated from rural tribal rules and many remained unmarried or divorced during long periods, this being 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.
Colonialism in Africa
Amit
Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged
epidemically as a result of 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 research established that
these theories were mostly correct: HIV-1 groups M and O started to
spread in humans in late 19th–early 20th century. In addition, 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).
This theory was later dubbed "Heart of Darkness" by Jim Moore, alluding to the book of the same title written by Joseph Conrad, 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 (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 the 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 variants 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.
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 evolution of sexual activity
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.
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
(either or both of clitoridectomy and infibulation) is responsible for
the high incidence of AIDS in Africa, since intercourse with a female
who has undergone clitoridectomy is conducive to exchange of blood.
Male circumcision distribution and HIV origins
Male circumcision may reduce the probability of HIV acquisition by men. Leaving aside blood transfusions, the highest HIV-1
transmissibility ever measured was from female prostitutes with 85%
prevalence of HIV to uncircumcised men with GUD—"A cumulative 43% ...
seroconverted to HIV-1 after a single sexual exposure." There was no
seroconversion in the absence of male GUD. 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 activity 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 [sic] 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 centred on the role of parenteral risks, such as unsterile injections, transfusions, or smallpox vaccinations are accepted as plausible by most scientists of the field.
Discredited HIV/AIDS origins theories include several iatrogenic theories, such as the polio vaccine hypothesis which argues that the early oral polio vaccines were contaminated with a chimpanzee virus, leading to 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 mistakenly referred to 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 patient
with AIDS in the 1990s. 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
A second early documented HIV-1 infection was discovered in a preserved lymph node biopsy sample taken in 1960 from a woman from Léopoldville, Belgian Congo.
1966: Congolese man
A strain with a large amount of the genetic material present was dated to 1966 from a sample from a 38-year-old man.
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.
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 (67%) of the
children.
1976: 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).
1976: Grethe Rask
Grethe Rask: A Danish surgeon who traveled to Zaïre
in 1964 then again in 1972 to aid the sick. She was likely directly
exposed to blood from many Congolese patients, one of whom infected her.
She became unwell from 1974, then returned to Denmark
in 1977, with her colleagues baffled by her symptoms. She died of
pneumocystis pneumonia in December 1977. Her tissues were examined and
tested by her colleagues and found positive in 1987.
Spread to the Western Hemisphere
Further
occurrences of this infection may have been emerging as early as 1966.
The virus eventually entered gay male communities in large United States
cities, where a combination of casual, multi-partner sexual activity
(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 "Case 057" and later "Patient O" with the alphabet
letter "O" standing for "outside Southern California", 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 taking HIV to North America. However, HIV reached New York City around 1971 while Dugas did not start work at Air Canada until 1974. In Randy Shilts' 1987 book And the Band Played On (and the 1993 movie based on it), Dugas is referred to as AIDS's Patient Zero
instead of "Patient O", but neither the book nor the movie states that
he had been the first to bring the virus to North America. He was
incorrectly 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 a
person who had sexual intercourse with Dugas.
Homeless people and intravenous drug users in New York
A volunteer social worker called Betty Williams, a Quaker who worked with the homeless in New York
from the seventies and early eighties onwards, has talked about people
at that time whose death would be labelled as "junkie flu" or "the
dwindles".
In an interview for the Act Up Oral History Project in 2008, she said:
"Of course, the horror stories came, mainly concerning women who were injection-drug users ... who had PCP pneumonia (Pneumocystis pneumonia), and were told that they just had bronchitis."
She continues: "I actually believe that AIDS kind of existed among this
group of people first, because if you look back, there was something
called junkie pneumonia, there was something called the dwindles that
addicts got, and I think this was another early AIDS population way too
helpless to ever do anything for themselves on their own behalf."
Julia Epstein writes in her book Altered Conditions: Disease, Medicine and Storytelling
that: "As we uncover more of the early history of HIV infection, it
becomes clear that by at least the 1970s the virus was already making
major inroads into the immune systems
of a number of diverse populations in the United States (the
retrospectively diagnosed epidemic of 'junkie pneumonia' in New York
City in the late 1970s for example) and had for some time been causing
devastation in several countries in Africa."
Anecdotal evidence suggests that so-called junkie pneumonia first began to afflict heroin addicts in New York in 1977. In her book EnGendering AIDS: Deconstructing Sex, Text, and Epidemic, Tamsin Wilton
writes: "People had been sickening and dying of mysterious conditions
since the early 1970s, conditions that we can retrospectively diagnose
as AIDS related.
There was, for example, a phenomenon known as 'junkie pneumonia' which
spread among some populations of injecting street drug users in the
1970s, and which is now believed to have been caused by HIV infection."
Melinda Cooper writes in her book Family Values: Between Neoliberalism and the New Social Conservatism:
"It is plausible that these cases [of AIDS] did not come to light in
the 1970s for the same reason that 'junkie pneumonia' was not recognized
as the sign of an emerging infectious disease: The people in question
had such precarious access to health care that news of their death was
never communicated to public health authorities."
An article by Pattrice Maurer in the newspaper Agenda from April 1992 explores some of the issues surrounding junkie pneumonia.
It starts: "In the late 1970s while the epidemic known as 'disco fever'
swept through the U.S., an epidemic known as 'junkie pneumonia' raged
among injection drug users in New York City." It continues: "Few people
were aware that large numbers of injections drug users were inexplicably
dying of pneumonia. Those few who did notice these deaths did not feel
compelled to investigate the public health puzzle they posed."
The author's opinion is that if anyone had bothered to investigate
these deaths, they would have found an immune system disorder that is
now called AIDS.
Steven Thrasher writes in The Guardian: "Indeed, those of
us who study AIDS have long known that long before common symptoms such
as Kaposi sarcoma and pneumonia were showing up among hemophiliacs and
gay men, they were likely affecting homeless people who lived off
society’s radar, people who used IV (intravenous) drugs and those who
avoided medical treatment out of fear."
A chapter in The Proceedings of the World Conference of Therapeutic Communities
(9th, San Francisco, California, September 1–6, 1985) gives details
about serum samples that were tested for signs of HIV (then called
HTLV-III/LAV) antibodies. Quoting: "We have also conducted historical studies of the epidemic in New York City, using serum samples
that were originally collected for other purposes. We have sera from IV
drug users that go back to the middle 1960s. The first indication of
HTLV-III/LAV antibody presence is in one of eleven samples from 1978 ...
29% of 40 samples in 1979 ... 44% of samples from 1980 and 52% of
samples from 1982. The HTLV-III/LAV virus appears to have been
introduced among IV drug users in the late 1970s in New York City."
Anna Thompson writes on the website TheBody.com in an article
dated Autumn 1993: "Many women were dying in the late '70s of pneumonia,
cervical cancer, and other illnesses complicated by 'mysteriously'
suppressed immune systems. Yet, it was not until 1981 that a case of
AIDS in a woman was first reported by the Centers for Disease Control
(CDC)." She continues: "The CDC's refusal to address women's issues led to the overall perception that women do not get AIDS."
In an article published in AIDS: Cultural Analysis/Cultural Activism, author Douglas Crimp draws attention to anecdotal evidence about junkie pneumonia. Quoting: "Even these statistics are based on CDC epidemiology
that continues to see the beginning of the epidemic as 1981 ... in
spite of widespread anecdotal reporting of a high rate of deaths
throughout the 1970s from what was known as 'junkie pneumonia' and was
likely Pneumocystis pneumonia." The statistics Crimp writes about were taken from a New York Times
article from October 1987 about a NYC Department of Health study that
showed that 53% of AIDS sufferers were people who injected drugs – more
than 150 percent higher than previously reported.
Quoting: "City health officials estimated that half of the city's
200,000 intravenous drug users were infected with the virus that causes
AIDS".
The study "HIV-1 Infection Among Intravenous Drug Users in
Manhattan, New York City, from 1977 through 1987", published in February
1989, seeks to understand long term trends in the spread of HIV among
intravenous drug users (IDUs).
AIDS surveillance data and studies which detail the number of persons
who tested HIV positive in Manhattan are used to compile information
deemed critical to realising the extent of the AIDS epidemic. It starts
by stating that up to September 1988, IDU was the risk behaviour in
19,139 (or 26%) of the first 72,223 cases of AIDS in the US.
Cases among IDUs in New York in the same period numbered 6,182
(approximately a third of national IDU cases). The study continues to
outline the methodology used in the compilation of data. It says that
while truly representative samples of IDUs within a community are
probably impossible to obtain, samples of IDUs entering treatment
provide a good source for monitoring trends. In the results section it
states (quoting): "The first evidence for HIV-1 infection among IV drug
users in New York is from three cases of AIDS in children born in 1977.
These cases were later reported to the New York City Department of
Health AIDS Surveillance Unit. These children did not receive any known transfusions prior to developing AIDS and were born to mothers known to be IV drug users."
It continues to outline that the earliest known case of AIDS in
an adult IDU occurred in 1979 (mixed risk) and that known cases among
IDUs increased rapidly from the 8 cases in 1980 (3 mixed risk), to 31
cases in 1981, to 160 cases in 1982, and to 340 cases in 1983.
Statistics on the incidence of positive tests for HIV, mainly using
archived samples, are: 1978 1 out of 11; 1979 13/50; 1980 8/21; 1981–83
14/28; 1984 75/137 and 38/63; 1986 36/55 and 1987 169 out of 294. In the comments section, it states: "The three cases in 1977 of apparent perinatal transmission
(mother-to-child) from IV drug-using women strongly suggest that the
introduction of HIV-1 into the IV drug-use group occurred around 1975 or
1976, or perhaps even earlier."
It says that without extensive samples from this period, it is not
possible to be certain about the spread of HIV among IDUs, but the
samples from IDUs with chronic liver disease suggest that the rates of infection were below 20% for the first 3 or 4 years after its introduction.
HIV is thought to have entered the population of people using intravenous drugs in New York in approximately 1975.
In Spring 1975, the government of New York underwent a fiscal crisis
which led to the closing of many social services, with people who used
intravenous drugs living in a hostile sociopolitical and legal
environment.
This fiscal crisis led to many agencies with health responsibilities
being particularly hard hit, which in turn might have led to an increase
in HIV/AIDS and Tuberculosis (TB). Quoting from a 2006 American Journal of Public Health
study: "Between 1974 and 1977, the Department of Health (DOH) budget
(in NY) was cut by 20%, and by 1977 the department had lost 1700 staff
members – 28% of its 1974 workforce. To achieve these reductions, the
department closed 7 of 20 district health centers, cut $1 million from
its methadone program, terminated the employment of 14 of 19 health
educators, and closed 20 of 75 child health stations and 6 of 14 chest
clinics (the units responsible for TB screening and diagnosis)."
A study published in the Journal of the American Medical Association in 1986 links TB and HIV/AIDS.
Quoting: ""Severe and unusual presentation of overwhelming tuberculosis
in appropriate clinical circumstances may be considered an infection predictive
of the presence of AIDS." Further, a study from 1987 states there was a
link between the rise in TB, AIDS and drug users within the United
States.
Quoting: "AIDS thus compounds the risk of acquiring tuberculosis, and
in the United States most patients with AIDS and tuberculosis have been
drug users."
A newsletter from Spring 1987 by the National Coalition Of Gay STD
Services has an article titled "Tuberculosis and AIDS - Connecticut"
that suggests an association between TB and AIDS within that state.
1981–1982: 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. The syndrome was initially termed "GRID", or "gay-related immune deficiency"; other less common gay-specific terms included "gay compromise syndrome",
"gay lymph node syndrome", "gay cancer", "gay plague", "homosexual
syndrome", "community-acquired immunodeficiency" ("CAID") and "acquired
community immunodeficiency syndrome" ("ACIDS"). Health authorities soon realized, however, that nearly half of the people identified with the syndrome were not homosexual men. The same opportunistic infections were also reported among hemophiliacs, users of intravenous drugs such as heroin, 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).
Activism by AIDS patients and families
In New York City, Nathan Fain, Larry Kramer, Larry Mass, Paul Popham, Paul Rapoport, and Edmund White officially established the Gay Men's Health Crisis (GMHC) in 1982.
Also in 1982, Michael Callen and Richard Berkowitz published How to Have Sex in an Epidemic: One Approach.
In this short work, they described ways gay men could be sexual and
affectionate while dramatically reducing the risk of contracting or
spreading HIV. Both authors were themselves gay men living with AIDS.
This booklet was one of the first times men were advised to use condoms
when having sexual relations with other men.
At the beginning of the AIDS epidemic in the 1980s, there was
very little information about the disease. Also, because AIDS affected
stigmatized groups, such as LGBTQ and people of low socioeconomic
status, there wasn't much mass media coverage initially when the
epidemic started.
However, with the rise of activist groups composed of people suffering
from AIDS, either directly or through a loved one, more public attention
was brought to the epidemic.
Identification of the virus
May 1983: LAV
In May 1983, a team of doctors at the Pasteur Institute in France including Françoise Barré-Sinoussi and Luc Montagnier 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
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 .
August 1984: ARV
Dr.
Jay Levy's group at the University of California, San Francisco also
played a role in the discovery of HIV. He independently isolated the
AIDS virus in 1983 and named it the AIDS-associated Retrovirus (ARV),
publishing his findings in the journal Science in 1984.
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—indeed, it was later determined that the virus isolated by
the Gallo lab was from the lymph nodes of the patient studied in the
original 1983 report by Montagnier—and was the etiological agent of AIDS.
May 1986: the name HIV
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.
Nobel
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." Dr Levy's contribution to the discovery of HIV was also cited in the Nobel Prize ceremony.
Case definition for epidemiological surveillance
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.
Genetic studies
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 in the period when Madagascar was still 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 mammals.
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.
A 2016 Czech study of the genome of Malayan flying lemurs,
an order of mammals parallel to primates and sharing an immediate
common ancestor with them, found endogenous lentiviruses that emerged an
estimated 40–60 million years ago based on rates of viral mutation
versus modern lentiviruses.
Discredited hypotheses
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. Both forms of AIDS
denialism have been rejected by scientific consensus. The evidence that HIV causes AIDS is generally considered conclusive among pathologists. Most arguments for denialism are based on misrepresentations of outdated data. The belief that HIV was created by the US government as a bioweapon, an idea invented by a Soviet propaganda operation, is held by a disproportionately high number of Africans and African-Americans.
