HIV AIDS historical perspective
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6] ;Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [7]
Overview
The first reported case of AIDS by CDC was in 1981, June 5 after which in 1982 the term AIDS was coined. Although many cases have been identified as AIDS since then , earliest cases of AIDS can be traced back to 1959 in Congo. A wide variety of theories has been postulated of the possible transmission of AIDS from animals to human like from Cameroon Chimpanzees and Congo Macaques. 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.
Historical Perspective
AIDS was sometimes informally called the gay plague or GRIDS (Gay-related immune deficiency syndrome), a name proposed after public health scientists noticed clusters of Kaposi's sarcoma and Pneumocystis pneumonia among gay males in California and New York City.[1] During the early history of AIDS, an ad hoc organization called Gay Men's Health Crisis was founded to combat what was then thought to be a homosexual-only disease perhaps produced by high levels of promiscuity, intravenous drug use, and usage of poppers. Soon after, clusters of Kaposi's sarcoma and Pneumocystis pneumonia were also reported among Haitians recently entering the United States[2] and men with haemophilia, among female sexual partners of AIDS patients, among children born to possibly infected mothers, and among blood transfusion recipients with no obvious risk factors. The term AIDS (for acquired immune deficiency syndrome) was proposed in 1982[3] by Bruce Voeller, among other researchers, concerned with the accuracy of the disease's name. In this new name, scientists were supported by political figures who realized that the term "gay-related" did not accurately describe the demographic that the disease affected.
In April 23, 1984, U.S. Department of Health and Human Services Secretary Margaret Heckler announced at a press conference that an American scientist, Dr. Robert Gallo, had discovered the probable cause of AIDS: the retrovirus subsequently named human immunodeficiency virus or HIV in 1986. The virus had previously been discovered by researchers at the Pasteur Institute in France, who called it lymphadenopathy-associated virus. It was given the acronym LAV and was subsequently renamed HIV.
After twenty years of research, both Kaposi's sarcoma and Pneumocystis pneumonia are better understood as opportunistic infections occurring towards the end of the AIDS disease process.
- AIDS was first reported June 5, 1981, when the U.S. Centers for Disease Control and Prevention recorded a cluster of Pneumocystis carinii pneumonia (classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles.[4] By year-end of 1981, there is a cumulative total of 270 reported cases of severe immune deficiency among gay men, and 121 of those individuals have died.
- On September 24 1982, CDC uses the term “AIDS” (acquired immune deficiency syndrome) for the first time, and releases the first case definition of AIDS: “a disease at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known case for diminished resistance to that disease.
- Three of the earliest known instances of HIV infection are:
- A plasma sample taken in 1959 from an adult male living in Kinshasa, today part of the Democratic Republic of the Congo.[5]
- HIV found in tissue samples from "Robert R.", a 15 year old African-American teenager who died in St. Louis in 1969.
- HIV found in tissue samples from Arvid Noe, a Norwegian sailor who died around 1976.[6]
- 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 not as easily transmitted and is largely confined to West Africa.[7] Both HIV-1 and HIV-2 are of primate origin. The origin of HIV-1 is the Central Common Chimpanzee (Pan troglodytes troglodytes) found in southern Cameroon.[8] It is established that HIV-2 originated from the Sooty Mangabey (Cercocebus atys), an Old World monkey of Guinea Bissau, Gabon, and Cameroon.
- Most experts believe that HIV probably transferred to humans as a result of direct contact with primates, for instance during hunting or butchery.[9]
- A more controversial theory known as the OPV AIDS hypothesis suggests that the AIDS epidemic was inadvertently started in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a poliomyelitis vaccine. According to scientific consensus, this scenario is not supported by the available evidence.[10][11][12]
- A recent study states that HIV probably moved from Africa to Haiti and then entered the United States around 1969.[13]
1985 World Health Organization AIDS Surveillance Case Definition
The 1985 World Health Organization AIDS surveillance case definition was developed in October 1985, at a conference of public health officials including representatives of the Centers for Disease Control (CDC) and World Health Organization (WHO) in Bangui, Central African Republic. For this reason, it became to be known as the Bangui definition for AIDS. It was developed to provide surveiling case definition of AIDS for use in countries where testing for HIV antibodies was not available.
It stated the following:
Exclusion criteria
- Pronounced malnutrition
- Cancer
- Immunosuppressive treatment
| Inclusion criteria with the corresponding score | Score |
|---|---|
| Important signs | |
|
4 |
|
4 |
| Very frequent signs | |
|
3 |
|
3 |
| Other signs | |
| 2 | |
| 2 | |
| 4 | |
|
4 |
|
4 |
|
4 |
|
2 |
|
2 |
|
12 |
The diagnosis of AIDS is established when the score is 12 or more.
The 1985 WHO AIDS surveillance case definition was heavily criticised, for both medical and political reasons. The 1994 expanded World Health Organization AIDS case definition was introduced in 1994 to incorporate the statement that HIV testing should be done. However, if testing was unavailable, then the Bangui definition should be used.
1994 Expanded World Health Organization AIDS Case Definition
The 1994 expanded World Health Organization AIDS case definition came around through the developments in the understanding of the spectrum of severe HIV-related illness both in developed and developing countries, and the increased availability of laboratory diagnostic methods, a meeting was convened in Geneva, Switzerland by the World Health Organization Global Programme on AIDS to review the 1985 World Health Organization AIDS surveillance case definition (Bangui definition) and to modify and expand them for use in adults and adolescents. Both the 1985 World Health Organization AIDS surveillance case definition and the 1994 expanded World Health Organization AIDS case definition are case definitions for AIDS surveillance and not for clinically staging HIV infection.
The main change from the Bangui definition is the addition of an HIV test for HIV antibody. If this test gives a positive result and one or more of the following conditions, the individual is considered to have AIDS.
- > 10% body weight loss or cachexia, with diarrhoea or fever, or both, intermittent or constant for at least 1 month, not known to be due to a condition unrelated to HIV infection.
- Cryptococcal meningitis
- Pulmonary or extra-pulmonary tuberculosis
- Kaposi's sarcoma
- Neurological impairment that is sufficient to prevent independent daily activities, not known to be due to a condition unrelated to HIV infection (for example, trauma, or cerebrovascular accident).
- Candiasis of the oesophagus (which may be presumptively diagnosed based on the presence of oral candiasis accompanied by dysphagia.
- Clinically diagnosed life-threatening or recurrent episodes of pneumonia, with or without etiological confirmation
- Invasive cervical cancer
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Durban Declaration
The Durban declaration was a statement signed by over 5,000 physicians and scientists at the 2000 International AIDS Conference in Durban, South Africa, affirming that HIV is the cause of AIDS. The declaration was drafted in response to statements by South Africa president Thabo Mbeki, who questioned the link between HIV and AIDS. At the Durban conference, 5,000 scientists from all over the world, including eleven Nobel prize winners, signed a statement calling the evidence that HIV causes AIDS "clear-cut, exhaustive and unambiguous."[14]
Famous Cases
David Carr
David Carr (November 1933 - August 31, 1959) was a sailor from Reddish, Manchester. He died at a relatively young age owing to multiple complications that were at the time inexplicable to his doctors at the Manchester Royal Infirmary. In 1990, more than three decades after his death, stored tissue samples from his body were tested positive for HIV. Given the date of his death, he was suspected to have been the first victim of AIDS in the West. The case gained wide coverage when the Sunday Express printed an exposé that revealed Carr's identity to the public. However, further tests were carried out in the mid-1990s by the eminent American scientist Dr David Ho, who found that Carr's tissue samples had been contaminated and who thus disproved the earlier AIDS diagnosis. Carr's case is extensively documented in Edward Hooper's massive work on the history of AIDS, The River.
1955-1957: British Sailor
The oldest documented case of the then-unknown syndrome was thought to have been detected that same year, when a 25-year-oldBritish sailor who had traveled 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 thempurplish skin lesions, for nearly two years. His condition had taken a turn for worse during Christmas1958, 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 andPneumocystis carinii pneumonia (PCP, later, when redetermined as P. jirovecii, renamedPneumocystis 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 eventually 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 admitted that the tissue sample was 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 infection was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo).[15] However, it is unknown whether this anonymous person ever developed AIDS and died of its complications. [5]
1959: Haitian Clerk
Another early case was probably detected that same year, 1959, in a 48-year-old Haitian, who 30 years before had immigrated to the United States and at the time was working as a shipping clerk for a garment manufacturer in Manhattan. He developed similar symptoms to those just described for the British sailor, and died the same year, apparently of the same very rare kind of pneumonia. Many years later, Dr. Gordon R. Hennigar, who had performed this man's autopsy, was asked whether he thought his patient had died of AIDS; he replied "You bet" and added "It was so unusual at the time. Lord knows how many cases of AIDS have been autopsied that we didn't even know had AIDS. I think it's such a strong possibility that I've often thought about getting them to send me the tissue samples."
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 atTulane 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.[16]
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, four years after he had spent time in ports along the West African coastline. Tissue samples from the sailor and his wife were tested in 1988 and found to contain the HIV-1 virus (Group O).[17][18] [6]
1977: Dr. Grethe Rask
The next documented western death from AIDS was that of Dr. Grethe Rask in 1977. Rask, a Danish surgeon, had worked in the Congo in the early 1970s.
Camp Bulkeley
Camp Bulkeley was a detention center located within the United States military base at Guantanamo Bay, Cuba, where HIV-positive refugees and asylum seekers were held during the early 1990s. After two years of protest, including a mention by presenters Susan Sarandon and Tim Robbins during the 1993 Academy Awards, the camp was declared unconstitutional by United States district court Judge Sterling Johnson Jr.. In a negotiated agreement with attorneys for the detainees, that decision was vacated and the camp was closed shortly thereafter.[19]
Gradual Spread
It appears that either HIV existed in very low levels in the United States in periods prior to1981, or it may have gone extinct in the United States at times, with the present infection established in the USA about1976. HIV in Africa likewise was at first at levels too low to be noticed. 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.
Author Randy Shilts mentioned that what was later called AIDS became evident in the gay community in the Fire Island, New York area in the four years after the 1976 Bicentennial celebrations. The infection tended to double in numbers about every nine to ten months. It therefore took a couple of years before a new disease was suspected because there were at first not enough symptomatic individuals to be noticed.
1981: Official start of Epidemic
The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention in itsMorbidity 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.[4]
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[20] and persistent, generalized lymphadenopathy [21]), common in immunosuppressed patients.
The disease was originally dubbed GRID, or Gay-Related Immune Deficiency, but health authorities soon realized that nearly half of the people identified with the syndrome were not homosexual men. In 1982, the CDC introduced the term AIDS to describe the newly recognized syndrome, though it was still casually referred to as GRID.
1982: The Name AIDS Appears
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,[22] and the syndrome was initially termed 'GRID' (Gay-Related Immune Deficiency). However, the same opportunistic infections also began to be reported amonghemophiliacs,[23] heterosexualintravenous drug users, and Haitian immigrants.[24]
By August 1982, the disease was being referred to by its new name: Acquired Immune Deficiency Syndrome (AIDS).[25] It got these names in other languages:-
- Afrikaans: VIGS (Verworwe Immuniteits Gebrek Sindroom)
- Portuguese: SIDA (Síndrome da Imunodeficiência Adquirida)
- French: SIDA: (Syndrome d'Immuno-Déficience Acquise)
- Spanish: SIDA: (Síndrome de Inmunodeficiencia Adquirida).
- Russian: SPID: (Синдром Приобретенного Имунно Дефицита)
- Irish Gaelic: SEIF (Siondróm Easpa Imdhíonachta Faighte)
Historical Theories of Transmission
A variety of theories exist explaining the transfer of HIV to humans, but no single hypothesis is unanimously accepted, and the topic remains controversial.
From Cameroon Chimpanzees (Contested)
The most widely accepted theory is so called 'Hunter' Theory according to which transference from ape to human most likely occurred when a human was bitten by an ape or was cut while butchering one, and the human became infected.
Researchers announced in May 2006 that HIV most likely originated in wild chimpanzees in the southeastern rain forests ofCameroon (modern East Province) [26] [8] rather than in Kinshasa, Democratic Republic of Congo (formerly Zaire), as had previously been believed. Seven years of research and 1,300 chimpanzee genetic samples led Dr. Beatrice Hahn of the University of Alabama, Birmingham, to identify chimpanzee communities near Cameroon's Sanaga River as the most likely originators. Presumably, someone in rural Cameroon was bitten by a chimp or was cut while butchering one and became infected with the ape virus. That person passed it to someone else.
Calculating based on a fixed mutation rate, the jump from chimpanzee to human likely occurred during the French colonial period (1919–1960). Comparative primatologist Jim Moore suggests that this may have been the result of colonial practices of forced labour, which could have suppressed the immune system of the initial hunter enough to allow the virus to infect and take hold. Likewise, forced immunisations (using one needle on many patients) may have sped the virus's spread through Cameroon and beyond.
The Times published an article in 1987 stating that WHO suspected some kind of connection with its vaccine program and AIDS-epidemic. The story was almost entirely based on statements given by one unnamed WHO advisor. The theory was supported only by weak circumstantial evidence and is now disproven by unraveling the genetic code of the virus and finding out that the virus dates back to the 1930s.
From Congo Macaques via OPV (Contested)
Freelance journalist Tom Curtis discussed one controversial possibility for the origin of HIV/AIDS in a 1992 Rolling Stone magazine article. He put forward what is now known as the OPV AIDS hypothesis, which suggests that AIDS was inadvertently caused in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a poliovaccine.
Although subsequently retracted due to libel issues surrounding its claims, the Rolling Stone article motivated another freelance journalist, Edward Hooper, to probe more deeply into this subject. Hooper's research resulted in his publishing a 1999 book, The River, in which he alleged that an experimental oral polio vaccineprepared using chimpanzee kidney tissue was the route through which simian immunodeficiency virus (SIV) crossed into humans to become HIV, thus starting the human AIDS pandemic.[27]
This theory is contradicted by an analysis of genetic mutation in primate lentivirus strains that estimates the origin of the HIV-1 strain to be around 1930, with 95% certainty of it lying between 1910 and 1950.[28]
In February 2000 one of the original developers of the polio vaccine, Philadelphia based Wistar Institute found from its stores a vial of the original vaccine used in the vaccination program. It was analyzed in April 2001 and no traces of either HIV-1 or SIV were found in the sample.[29] A second analysis showed that only macaque monkey kidney cells, which cannot be infected with SIV or HIV, were used to produce the vaccine.[30] While the analysis was done on only one vial of vaccine, some scientists have concluded that the polio vaccine theory of the origins of HIV is not possible.
However the sample tested was never used in the Congo nor was it ever claimed by Hooper that the original vaccines were contaminated, the OPV hypothesis claims instead that HIV was introduced in the Congo at the Stanlyvile laboratory as the local administers amplified the original vaccine using infected Chimp kidneys (local amplification was widely practiced at the time) for the 1 million to whom it was forcefully administered. As such there is no hard evidence to dismiss the OPV hypothesis.
Edward Hooper rejects the dates calculated using a fixed mutation rate on the basis that phylogenetic dating of "the most recombinogenic organisms known to medical science", immunodeficiency viruses, is "inherently incapable of making any allowance for recombination". [31][27]
Method of Spread
After the initial transfer of HIV from a non-human primate to humans, 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:
- A large human population,
- A large nearby population of the appropriate host animal,
- An infectious pathogen in the host animal, that eventually produces a mutation that can spread from animal to human,
- Interaction between the species to transmit enough of it to humans to establish a human foothold, which may take millions of individual exposures,
- A mutation of same pathogen that can spread from human to human,
- 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 evolved from a Simian Immunodeficiency Virus (SIVcpz) found in the chimpanzee subspecies Pan troglodytes troglodytes.[32] DNA sequencing indicates that HIV-1 (group M) entered the human population in the early 20th century, probably sometime between 1915 and 1941.[33] HIV-2 crossed species from a different strain of SIV, this one found in sooty mangabeys (an Old World monkey) ofGuinea-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 SIV's 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.[34]
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.[35] 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).[36] [37]
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).[38] [39] The dual discovery led to considerable scientific disagreement, and it was not until President François Mitterrand of France and President Ronald Reagan of the USA met that the major issues were resolved.
Jan 1985: LAV/HTLV-III
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, from the same source, and was the etiological agent of AIDS[40] [41]
May 1986: 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. [42]
References
- ↑ "A Cluster of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia among Homosexual Male Residents of Los Angeles and range Counties, California". Retrieved 2007-01-24.
- ↑ "Opportunistic Infections and Kaposi's Sarcoma among Haitians in the United States". Retrieved 2007-01-24.
- ↑ "Time Magazine: A Name for the Plague". Retrieved 2007-01-24.
- ↑ 4.0 4.1 Gottlieb MS (2006). "Pneumocystis pneumonia--Los Angeles. 1981". Am J Public Health. 96 (6): 980–1, discussion 982–3. PMID 16714472.
- ↑ 5.0 5.1 Zhu T, Korber BT, Nahmias AJ; et al. (1998). "An African HIV-1 Sequence from 1959 and Implications for the Origin of the Epidemic". Nature. 391 (6667): 594&ndash, 597. doi:10.1038/35400. PMID 9468138.
- ↑ 6.0 6.1 Hooper E (1997). "Sailors and star-bursts, and the arrival of HIV". BMJ. 315 (7123): 1689&ndash, 1691. PMID 9448543.
- ↑ Reeves JD, Doms RW (2002). "Human Immunodeficiency Virus Type 2". J. Gen. Virol. 83 (Pt 6): 1253&ndash, 1265. PMID 12029140.
- ↑ 8.0 8.1 Keele BF, van Heuverswyn F, Li YY; et al. (2006). "Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1". Science. 313 (5786): 523–6. doi:10.1126/science.1126531. PMID 16728595.
- ↑ Cohen J (2000). "Vaccine Theory of AIDS Origins Disputed at Royal Society". Science. 289 (5486): 1850&ndash, 1851. doi:10.1126/science.289.5486.1850. PMID 11012346.
- ↑ Worobey M, Santiago ML, Keele BF; et al. (2004). "Origin of AIDS: contaminated polio vaccine theory refuted". Nature. 428 (6985): 820. doi:10.1038/428820a. PMID 15103367.
- ↑ Berry N, Jenkins A, Martin J; et al. (2005). "Mitochondrial DNA and retroviral RNA analyses of archival oral polio vaccine (OPV CHAT) materials: evidence of macaque nuclear sequences confirms substrate identity". Vaccine. 23: 1639&ndash, 1648. doi:10.1016/j.vaccine.2004.10.038. PMID 15705467.
- ↑ "Oral Polio Vaccine and HIV / AIDS: Questions and Answers". Centers for Disease Control and Prevention. 2004-03-23. Retrieved 2006-11-20.
- ↑ Gilbert MT, Rambaut A, Wlasiuk G, Spira TJ, Pitchenik AE, Worobey M (2007). "The emergence of HIV/AIDS in the Americas and beyond". Proc. Natl. Acad. Sci. U.S.A. 104 (47): 18566–70. doi:10.1073/pnas.0705329104. PMID 17978186.
- ↑ "The Durban Declaration". Nature. 406 (6791): 15–6. 2000. PMID 10894520.
- ↑ [1]
- ↑ [2]
- ↑ [3]
- ↑ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2897596&dopt=Abstract
- ↑ LastName, FirstName (2007). Visit to Guantánamo Bay. London: The Stationery Office. ISBN 0-215-03201-2. Check
|isbn=value: invalid character (help). - ↑ MMWR Weekly, June 11, 1982
- ↑ MMWR Weekly, May 21, 1982
- ↑ MMWR Weekly, June 18, 1982
- ↑ MMWR Weekly, July 16, 1982
- ↑ MMWR Weekly July 09, 1982
- ↑ Marx et al., 1982
- ↑ Gao, F., Bailes, E., Robertson, D. L., Chen, Y., Rodenburg, C. M., Michael, S. F., Cummins, L. B., Arthur, L. O., Peeters, M., Shaw, G. M., Sharp, P. M., and Hahn, B. H. (1999). "Origin of HIV-1 in the Chimpanzee Pan troglodytes troglodytes". Nature. 397 (6718): 436–441. doi:10.1038/17130. PMID 9989410.
- ↑ 27.0 27.1 Hooper, E. (1999). The River : A Journey to the Source of HIV and AIDS (1st ed.). Boston, MA: Little Brown & Co. pp. 1–1070. ISBN 0-316-37261-7.
- ↑ Korber B, Muldoon M, Theiler J; et al. (January 30 – February 2, 2000). "Timing the origin of the HIV-1 pandemic". Programs and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections. Abstract L5. (Online version at United States National Library of Medicine)
- ↑ Blancou, P. et al. "Polio vaccine samples not linked to AIDS" Nature: 410, p. 1045-1046 (2001)
- ↑ Blancou, P. et al. "Polio vaccine samples not linked to AIDS" Nature: 410, p. 1045-1046 (2001)
- ↑ Ed Hooper. Retrieved December 6, 2006.
- ↑ [4]
- ↑ [5]
- ↑ Schindler M, Münch J, Kutsch O; et al. (2006). "Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1". Cell. 125: 1055&ndash, 67. doi:10.1016/j.cell.2006.04.033.
- ↑ et al., 1983
- ↑ Connor and Kingman, 1988 (ISBN 0-14-011397-5)
- ↑ Barré-Sinoussi, F., Chermann, J. C., Rey, F., Nugeyre, M. T., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., Vezinet-Brun, F., Rouzioux, C., Rozenbaum, W. and Montagnier, L. (1983). "Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)". Science. 220 (4599): 868–871. PMID 6189183.
- ↑ Popovic, M., Sarngadharan, M. G., Read, E. and Gallo, R. C. (1984). "Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS". Science. 224 (4648): 497–500. PMID 6200935.
- ↑ et al., 1984
- ↑ Marx, 1985
- ↑ et al., 1993
- ↑ Coffin et al., 1986
- Pages with reference errors
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