History of HIV/AIDS

Scanning electron micrograph of HIV-1 budding from cultured lymphocyte.

HIV, the infectious agent that causes AIDS, is thought to have originated in non-human primates in sub-Saharan Africa and to have been transferred to humans during the 20th century.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-2 may have originated from the Sooty Mangabey (Cercocebus atys), an Old World monkey of Guinea-Bissau, Gabon, and Cameroon. HIV-1 is more virulent. It is easily transmitted and is the cause of the majority of HIV infections globally. HIV-2 is less transmittable and is largely confined to West Africa. HIV-1 is the species described below.

Likely spread from animal to human populations

Most HIV researchers agree that HIV evolved from the closely related Simian Immunodeficiency Virus (SIV), and that HIV was transferred from non-human primates to humans in the recent past (as a type of zoonosis). The details of how and where this occurred remain controversial, and no single hypothesis has been unanimously accepted.

Cameroon chimpanzees hypothesis

The currently accepted hypothesis is the so-called 'Hunter' Theory, according to which a human bushmeat hunter was bitten or cut while hunting or butchering an ape, resulting in infection. Exactly where and when this occurred has been a matter of debate in the scientific community. Researchers announced in May, 2006 that HIV-1 most likely originated in wild chimpanzees in the southeastern rain forests of Cameroon (modern East Province). Others place the origin of HIV-1 closer to Kinshasa. Seven years of research and 1,300 chimpanzee genetic samples led Dr. Beatrice Hahn, of the University of Alabama at Birmingham, to identify chimpanzee communities near Cameroon's Sanaga River as the most likely original reservoir of HIV-1.

Calculations based on viral mutation rates and HIV-1 sequences preserved in biological samples in 1959 ("ZR59") and 1960 (DRC60) suggest that the jump from chimpanzee to human likely happened during the late 19th century or the early 20th century, a time of rapid urbanisation in the colonial period. Comparative primatologist Jim Moore suggests that colonial practices may have created conditions conducive to the spread of the virus. The hardships of forced labour could have suppressed the immune system of the initial hunter, allowing the virus to infect and take hold in a new host. Rapid urbanisation brought infected people into close contact with others, and colonial commerce provided opportunities for further geographical spread. Vaccination campaigns against illnesses such as sleeping sickness may have sped the initial spread of HIV-1 when immunisation needles were re-used, and needles were also shared in the booming colonial city of Kinshasa. Other technological and social disruptions, especially those that affected the food supply and the hunting of bushmeat, are thought to have promoted the cross-over from chimpanzees and the spread amongst humans.

Oral polio vaccine hypothesis

Main article: OPV AIDS hypothesis

The hypothesis that HIV/AIDS originated from polio vaccine research in Africa was popularized by an article in Rolling Stone and books by the journalist Edward Hooper. This hypothesis was subsequently investigated and rejected by the scientific community; an expert panel convened in 1992 found every step in the hypothesis "problematic", and concluded that "it can be stated with almost complete certainty that the large polio vaccine trial... was not the origin of AIDS."

Subsequent research has falsified the basic claims of the oral polio vaccine hypothesis, leading a 2001 editorial in Nature to conclude:

The new data may not convince the hardened conspiracy theorist who thinks that contamination of OPV by chimpanzee virus was subsequently and deliberately covered up. But those of us who were formerly willing to give some credence to the OPV hypothesis will now consider that the matter has been laid to rest.

Subsequent DNA analysis of HIV has shown it initially entered the human population in approximately 1908.

Method of spread

After the initial transfer of SIV from a non-human primate to humans, and the mysterious and sudden change or possible mutation into HIV, the virus ultimately spread via contact among humans to the rest of the world. Since a cross species jump is most likely the origin of HIV, and since HIV became a true epidemic, transmissible from human to human, then the following conditions were needed:

1. a large human population;
2. a large nearby population of the appropriate host animal;
3. an infectious pathogen in the host animal, that eventually produces a mutation that can spread from animal to human;
4. interaction between the species to transmit enough of it to humans to establish a human foothold, which may take millions of individual exposures;
5. a mutation of same pathogen that can spread from human to human;
6. some method that allows the pathogen to disperse widely. This prevents the infection from "burning out" by either killing off its human hosts or provoking immunity in a local population of humans.

Such requirements existed in the remote past with smallpox, and also with the 20th century Spanish flu, despite Spanish flu's New World origin at Fort Riley, Kansas. There the animal reservoir seems to have been two species, chickens and pigs, which were of Old World origin.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily transmitted. HIV-1 is the source of the majority of HIV infections throughout the world, while HIV-2 is less easily transmitted and is largely confined to West Africa.

Both species of the virus (HIV-1 and HIV-2) are believed to have originated in West-Central Africa and jumped species (zoonosis) from a non-human primate to humans. HIV-1 somehow came from Simian Immunodeficiency Virus (SIV_cpz) found in the chimpanzee subspecies Pan troglodytes troglodytes. DNA sequencing indicates that HIV-1 (group M) entered the human population in the early 20th century, probably sometime between 1915 and 1941. A 2008 paper using a recently-discovered 1960 biopsy suggested a common ancestor between 1884 and 1924. HIV-2 crossed species from a different strain of SIV, this one found in sooty mangabeys (an Old World monkey) of Guinea-Bissau.

SIVs in non-human primates tend to cause non-fatal disease. 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 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.

History of known cases and spread

1955–1957: British printer (incorrectly reported as an AIDS death)

The oldest documented possible case of the then-unknown syndrome was thought to have been detected in 1959, when a 25-year-old British printer who had travelled in the navy between 1955 and 1957 (but apparently not to Africa) sought help at the Royal Infirmary of Manchester, England. He reported to have been suffering from puzzling symptoms, among them purplish skin lesions, for nearly two years. His condition had taken a turn for worse during Christmas 1958, when he started suffering from shortness of breath, extreme fatigue, rapid weight loss, night sweats and high fever. The doctors thought he might be suffering from tuberculosis and, even though they found no evidence of bacterial infection, they treated him for tuberculosis just to be safe, to no avail. The sailor 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, when redetermined as P. jirovecii, renamed Pneumocystis pneumonia), very rare at the time but now commonly associated with AIDS patients. His case had puzzled his doctors, who preserved tissue samples from him and for years retained some interest in solving the mystery.

Sir Robert Platt, then president of the Royal College of Physicians, wrote in the sailor'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 the preserved tissues of the sailor, which initially turned out a positive result. The case was reported in the July 7, 1990 issue of the British medical journal The Lancet; their claim was retracted in a letter in the January 20, 1996 issue where they reported that the tissue sample had become contaminated in the laboratory (Corbitt G, Bailey A, Williams G. HIV infection in Manchester, 1959 . Lancet 1990; ii: 51.)

1959: Congolese man

One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo). However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.

1960: Congolese woman

A second early documented HIV-1 infection was discovered in a preserved lymph node biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.

1969: Robert R.

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

1969: Arvid Noe

In 1976, a Norwegian sailor named 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 gonorrhoea 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 the HIV-1 virus (Group O).

Gradual spread

A 2007 genetic study suggests that the HIV strains present in the early 1980s arrived in the United States from Haiti in the late sixties or early seventies. It is believed to have arrived in Haiti from central Africa, possibly through professional contacts with the newly independent Congo.

The disease has an incubation period of several years, and with a small incidence, was not noticed at first.

In the United States and Africa, HIV was at first mostly found only in residents of large cities. The infection is now more widespread in rural areas, and has appeared in regions such as China and India, where it was previously not evident.

1981–2: From GRID to AIDS

The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention in its Morbidity and Mortality Weekly Report newsletter reported unusual clusters of Pneumocystis pneumonia (PCP) caused by a form of Pneumocystis carinii (now recognized as a distinct species Pneumocystis jirovecii) in five homosexual men in Los Angeles.

Over the next 18 months, more PCP clusters were discovered among otherwise healthy men in cities throughout the country, along with other opportunistic diseases (such as Kaposi's sarcoma and persistent, generalized lymphadenopathy), common in immunosuppressed patients.

In June 1982, a report of a group of cases amongst gay men in Southern California suggested that a sexually transmitted infectious agent might be the etiological agent, and the syndrome was initially termed "GRID", or gay-related immune deficiency.

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

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

Genetic studies

A 2007 study published in the Proceedings of the National Academy of Sciences by Michael Worobey and Dr. Arthur Pitchenik claimed that, based on the results of genetic analysis, HIV probably moved from Africa to Haiti and then entered the United States around 1969.

A 2008 study published in Nature detailed the investigation of the differences between two of the earliest known genetic strains of HIV, and concluded that the original founding strain of the virus emerged between 1884 and 1924.

Identification of the virus

May 1983: LAV

In May 1983, doctors from Dr. Luc Montagnier's team at the Pasteur Institute in France, reported that they had isolated a new retrovirus from lymphoid ganglions that they believed was the cause of AIDS. The virus was later named lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers for Disease Control, which was later passed to the National Cancer Institute (NCI).

May 1984: HTLV-III

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).

Jan 1985: both found to be the same

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

May 1986: the name HIV

In May 1986, the International Committee on Taxonomy of Viruses ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used.

See also

• http://www.plwha.org
• CCR5-Δ32
• AIDS Conspiracy Theories
• Zoonosis