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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Feb;86(3):755–764. doi: 10.1073/pnas.86.3.755

Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation.

P H Duesberg 1
PMCID: PMC286556  PMID: 2644642

Abstract

AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa.(viii) It is highly improbable that within the last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between antibody to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albert J., Gaines H., Sönnerborg A., Nyström G., Pehrson P. O., Chiodi F., von Sydow M., Moberg L., Lidman K., Christensson B. Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection. J Med Virol. 1987 Sep;23(1):67–73. doi: 10.1002/jmv.1890230108. [DOI] [PubMed] [Google Scholar]
  2. Anand R., Siegal F., Reed C., Cheung T., Forlenza S., Moore J. Non-cytocidal natural variants of human immunodeficiency virus isolated from AIDS patients with neurological disorders. Lancet. 1987 Aug 1;2(8553):234–238. doi: 10.1016/s0140-6736(87)90826-9. [DOI] [PubMed] [Google Scholar]
  3. Anderson R. M., May R. M. Epidemiological parameters of HIV transmission. Nature. 1988 Jun 9;333(6173):514–519. doi: 10.1038/333514a0. [DOI] [PubMed] [Google Scholar]
  4. Andrewes C. H. The troubles of a virus. The seventh Marjory Stephenson Memorial Lecture. J Gen Microbiol. 1965 Aug;40(2):149–156. doi: 10.1099/00221287-40-2-149. [DOI] [PubMed] [Google Scholar]
  5. Andrieu J. M., Eme D., Venet A., Audroin C., Tourani J. M., Stern M., Israel-Biet D., Beldjord K., Driss F., Even P. Serum HIV antigen and anti-P24-antibodies in 200 HIV seropositive patients: correlation with CD4 and CD8 lymphocyte subsets. Clin Exp Immunol. 1988 Jul;73(1):1–5. [PMC free article] [PubMed] [Google Scholar]
  6. Barnes D. M. AIDS virus creates lab risk. Science. 1988 Jan 22;239(4838):348–349. doi: 10.1126/science.3336787. [DOI] [PubMed] [Google Scholar]
  7. Barnes D. M. AIDS: statistics but few answers. Science. 1987 Jun 12;236(4807):1423–1425. doi: 10.1126/science.3589664. [DOI] [PubMed] [Google Scholar]
  8. Barnes D. M. Obstacles to an AIDS vaccine. Science. 1988 May 6;240(4853):719–721. doi: 10.1126/science.2834823. [DOI] [PubMed] [Google Scholar]
  9. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  10. Baxter L. R., Jr, Schwartz J. M., Mazziotta J. C., Phelps M. E., Pahl J. J., Guze B. H., Fairbanks L. Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry. 1988 Dec;145(12):1560–1563. doi: 10.1176/ajp.145.12.1560. [DOI] [PubMed] [Google Scholar]
  11. Biberfeld P., Chayt K. J., Marselle L. M., Biberfeld G., Gallo R. C., Harper M. E. HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy. Am J Pathol. 1986 Dec;125(3):436–442. [PMC free article] [PubMed] [Google Scholar]
  12. Booth W. A rebel without a cause of AIDS. Science. 1988 Mar 25;239(4847):1485–1488. doi: 10.1126/science.3281251. [DOI] [PubMed] [Google Scholar]
  13. Booth W. CDC paints a picture of HIV infection in U.S. Science. 1988 Jan 15;239(4837):253–253. doi: 10.1126/science.2827306. [DOI] [PubMed] [Google Scholar]
  14. Centers for Disease Control (CDC) Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men--New York City and California. MMWR Morb Mortal Wkly Rep. 1981 Jul 3;30(25):305–308. [PubMed] [Google Scholar]
  15. Centers for Disease Control (CDC) Update: acquired immunodeficiency syndrome--United States. MMWR Morb Mortal Wkly Rep. 1985 May 10;34(18):245–248. [PubMed] [Google Scholar]
  16. Chayt K. J., Harper M. E., Marselle L. M., Lewin E. B., Rose R. M., Oleske J. M., Epstein L. G., Wong-Staal F., Gallo R. C. Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement. JAMA. 1986 Nov 7;256(17):2356–2359. [PubMed] [Google Scholar]
  17. Cheng-Mayer C., Seto D., Tateno M., Levy J. A. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. doi: 10.1126/science.2832945. [DOI] [PubMed] [Google Scholar]
  18. Clavel F. HIV-2, the West African AIDS virus. AIDS. 1987 Sep;1(3):135–140. [PubMed] [Google Scholar]
  19. Coffin J. M., Tsichlis P. N., Barker C. S., Voynow S., Robinson H. L. Variation in avian retrovirus genomes. Ann N Y Acad Sci. 1980;354:410–425. doi: 10.1111/j.1749-6632.1980.tb27982.x. [DOI] [PubMed] [Google Scholar]
  20. Coffin J., Haase A., Levy J. A., Montagnier L., Oroszlan S., Teich N., Temin H., Toyoshima K., Varmus H., Vogt P. Human immunodeficiency viruses. Science. 1986 May 9;232(4751):697–697. doi: 10.1126/science.3008335. [DOI] [PubMed] [Google Scholar]
  21. Colebunders R., Mann J. M., Francis H., Bila K., Izaley L., Kakonde N., Kabasele K., Ifoto L., Nzilambi N., Quinn T. C. Evaluation of a clinical case-definition of acquired immunodeficiency syndrome in Africa. Lancet. 1987 Feb 28;1(8531):492–494. doi: 10.1016/s0140-6736(87)92099-x. [DOI] [PubMed] [Google Scholar]
  22. Craighead J., Moore A., Grossman H., Ershler W., Frattini U., Saxinger C., Hess U., Ngowi F. Pathogenetic role of HIV infection in Kaposi's sarcoma of equatorial East Africa. Arch Pathol Lab Med. 1988 Mar;112(3):259–265. [PubMed] [Google Scholar]
  23. Crawford T. B., Adams D. S. Caprine arthritis-encephalitis: clinical features and presence of antibody in selected goat populations. J Am Vet Med Assoc. 1981 Apr 1;178(7):713–719. [PubMed] [Google Scholar]
  24. Curran J. W., Jaffe H. W., Hardy A. M., Morgan W. M., Selik R. M., Dondero T. J. Epidemiology of HIV infection and AIDS in the United States. Science. 1988 Feb 5;239(4840):610–616. doi: 10.1126/science.3340847. [DOI] [PubMed] [Google Scholar]
  25. Curran J. W., Morgan W. M., Hardy A. M., Jaffe H. W., Darrow W. W., Dowdle W. R. The epidemiology of AIDS: current status and future prospects. Science. 1985 Sep 27;229(4720):1352–1357. doi: 10.1126/science.2994217. [DOI] [PubMed] [Google Scholar]
  26. Cutlip R. C., Lehmkuhl H. D., Brogden K. A., Sacks J. M. Breed susceptibility to ovine progressive pneumonia (maedi/visna) virus. Vet Microbiol. 1986 Sep;12(3):283–288. doi: 10.1016/0378-1135(86)90057-x. [DOI] [PubMed] [Google Scholar]
  27. Dahl K., Martin K., Miller G. Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus. J Virol. 1987 May;61(5):1602–1608. doi: 10.1128/jvi.61.5.1602-1608.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Darrow W. W., Echenberg D. F., Jaffe H. W., O'Malley P. M., Byers R. H., Getchell J. P., Curran J. W. Risk factors for human immunodeficiency virus (HIV) infections in homosexual men. Am J Public Health. 1987 Apr;77(4):479–483. doi: 10.2105/ajph.77.4.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Delli Bovi P., Donti E., Knowles D. M., 2nd, Friedman-Kien A., Luciw P. A., Dina D., Dalla-Favera R., Basilico C. Presence of chromosomal abnormalities and lack of AIDS retrovirus DNA sequences in AIDS-associated Kaposi's sarcoma. Cancer Res. 1986 Dec;46(12 Pt 1):6333–6338. [PubMed] [Google Scholar]
  30. Douglas R. G., Jr, Couch R. B. A prospective study of chronic herpes simplex virus infection and recurrent herpes labialis in humans. J Immunol. 1970 Feb;104(2):289–295. [PubMed] [Google Scholar]
  31. Duesberg P. H. Cancer genes: rare recombinants instead of activated oncogenes (a review). Proc Natl Acad Sci U S A. 1987 Apr;84(8):2117–2124. doi: 10.1073/pnas.84.8.2117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Duesberg P. H. Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res. 1987 Mar 1;47(5):1199–1220. [PubMed] [Google Scholar]
  33. Duesberg P. HIV is not the cause of AIDS. Science. 1988 Jul 29;241(4865):514–517. doi: 10.1126/science.3399880. [DOI] [PubMed] [Google Scholar]
  34. Duesberg P. HIV is not the cause of AIDS. Science. 1988 Jul 29;241(4865):514–517. doi: 10.1126/science.3399880. [DOI] [PubMed] [Google Scholar]
  35. Duesberg P., Vogt P. K., Beemon K., Lai M. Avian RNA tumor viruses: mechanism of recombination and complexity of the genome. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):847–857. doi: 10.1101/sqb.1974.039.01.099. [DOI] [PubMed] [Google Scholar]
  36. Evans A. S. Causation and disease: a chronological journey. The Thomas Parran Lecture. Am J Epidemiol. 1978 Oct;108(4):249–258. doi: 10.1093/oxfordjournals.aje.a112617. [DOI] [PubMed] [Google Scholar]
  37. Evans A. S. Causation and disease: the Henle-Koch postulates revisited. Yale J Biol Med. 1976 May;49(2):175–195. [PMC free article] [PubMed] [Google Scholar]
  38. Eyster M. E., Gail M. H., Ballard J. O., Al-Mondhiry H., Goedert J. J. Natural history of human immunodeficiency virus infections in hemophiliacs: effects of T-cell subsets, platelet counts, and age. Ann Intern Med. 1987 Jul;107(1):1–6. doi: 10.7326/0003-4819-107-1-1. [DOI] [PubMed] [Google Scholar]
  39. Falk L. A., Jr, Paul D., Landay A., Kessler H. HIV isolation from plasma of HIV-infected persons. N Engl J Med. 1987 Jun 11;316(24):1547–1548. doi: 10.1056/NEJM198706113162413. [DOI] [PubMed] [Google Scholar]
  40. Farzadegan H., Polis M. A., Wolinsky S. M., Rinaldo C. R., Jr, Sninsky J. J., Kwok S., Griffith R. L., Kaslow R. A., Phair J. P., Polk B. F. Loss of human immunodeficiency virus type 1 (HIV-1) antibodies with evidence of viral infection in asymptomatic homosexual men. A report from the Multicenter AIDS Cohort Study. Ann Intern Med. 1988 Jun;108(6):785–790. doi: 10.7326/0003-4819-108-6-785. [DOI] [PubMed] [Google Scholar]
  41. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  42. Feinstein A. R. Scientific standards in epidemiologic studies of the menace of daily life. Science. 1988 Dec 2;242(4883):1257–1263. doi: 10.1126/science.3057627. [DOI] [PubMed] [Google Scholar]
  43. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  44. Fleming A. F. AIDS in Africa--an update. AIDS Forsch. 1988 Mar;3(3):116–138. [PubMed] [Google Scholar]
  45. Forster S. M., Osborne L. M., Cheingsong-Popov R., Kenny C., Burnell R., Jeffries D. J., Pinching A. J., Harris J. R., Weber J. N. Decline of anti-p24 antibody precedes antigenaemia as correlate of prognosis in HIV-1 infection. AIDS. 1987 Dec;1(4):235–240. [PubMed] [Google Scholar]
  46. Friedland G. H., Klein R. S. Transmission of the human immunodeficiency virus. N Engl J Med. 1987 Oct 29;317(18):1125–1135. doi: 10.1056/NEJM198710293171806. [DOI] [PubMed] [Google Scholar]
  47. Gajdusek D. C. Unconventional viruses and the origin and disappearance of kuru. Science. 1977 Sep 2;197(4307):943–960. doi: 10.1126/science.142303. [DOI] [PubMed] [Google Scholar]
  48. Gallo D., Kimpton J. S., Dailey P. J. Comparative studies on use of fresh and frozen peripheral blood lymphocyte specimens for isolation of human immunodeficiency virus and effects of cell lysis on isolation efficiency. J Clin Microbiol. 1987 Jul;25(7):1291–1294. doi: 10.1128/jcm.25.7.1291-1294.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Gallo R. C., Montagnier L. AIDS in 1988. Sci Am. 1988 Oct;259(4):41–48. [PubMed] [Google Scholar]
  50. Gallo R. C., Montagnier L. The chronology of AIDS research. Nature. 1987 Apr 2;326(6112):435–436. doi: 10.1038/326435a0. [DOI] [PubMed] [Google Scholar]
  51. Gallo R. C. The first human retrovirus. Sci Am. 1986 Dec;255(6):88–98. doi: 10.1038/scientificamerican1286-88. [DOI] [PubMed] [Google Scholar]
  52. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  53. Goedert J. J., Biggar R. J., Weiss S. H., Eyster M. E., Melbye M., Wilson S., Ginzburg H. M., Grossman R. J., DiGioia R. A., Sanchez W. C. Three-year incidence of AIDS in five cohorts of HTLV-III-infected risk group members. Science. 1986 Feb 28;231(4741):992–995. doi: 10.1126/science.3003917. [DOI] [PubMed] [Google Scholar]
  54. Gonda M. A., Wong-Staal F., Gallo R. C., Clements J. E., Narayan O., Gilden R. V. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science. 1985 Jan 11;227(4683):173–177. doi: 10.1126/science.2981428. [DOI] [PubMed] [Google Scholar]
  55. Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
  56. Goudsmit J., Lange J. M., Paul D. A., Dawson G. J. Antigenemia and antibody titers to core and envelope antigens in AIDS, AIDS-related complex, and subclinical human immunodeficiency virus infection. J Infect Dis. 1987 Mar;155(3):558–560. doi: 10.1093/infdis/155.3.558. [DOI] [PubMed] [Google Scholar]
  57. Groopman J. E., Hartzband P. I., Shulman L., Salahuddin S. Z., Sarngadharan M. G., McLane M. F., Essex M., Gallo R. Antibody seronegative human T-lymphotropic virus type III (HTLV-III)-infected patients with acquired immunodeficiency syndrome or related disorders. Blood. 1985 Sep;66(3):742–744. [PubMed] [Google Scholar]
  58. HUEBNER R. J. Criteria for etiologic association of prevalent viruses with prevalent diseases; the virologist's dilemma. Ann N Y Acad Sci. 1957 Apr 19;67(8):430–438. doi: 10.1111/j.1749-6632.1957.tb46066.x. [DOI] [PubMed] [Google Scholar]
  59. Haase A. T. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
  60. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  61. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Haseltine W. A., Wong-Staal F. The molecular biology of the AIDS virus. Sci Am. 1988 Oct;259(4):52–62. doi: 10.1038/scientificamerican1088-52. [DOI] [PubMed] [Google Scholar]
  63. Hearst N., Hulley S. B. Preventing the heterosexual spread of AIDS. Are we giving our patients the best advice? JAMA. 1988 Apr 22;259(16):2428–2432. [PubMed] [Google Scholar]
  64. Ho D. D., Pomerantz R. J., Kaplan J. C. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med. 1987 Jul 30;317(5):278–286. doi: 10.1056/NEJM198707303170505. [DOI] [PubMed] [Google Scholar]
  65. Ho D. D., Rota T. R., Hirsch M. S. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. doi: 10.1172/JCI112491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Ho D. D., Sarngadharan M. G., Hirsch M. S., Schooley R. T., Rota T. R., Kennedy R. C., Chanh T. C., Sato V. L. Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. J Virol. 1987 Jun;61(6):2024–2028. doi: 10.1128/jvi.61.6.2024-2028.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Hoxie J. A., Haggarty B. S., Rackowski J. L., Pillsbury N., Levy J. A. Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science. 1985 Sep 27;229(4720):1400–1402. doi: 10.1126/science.2994222. [DOI] [PubMed] [Google Scholar]
  68. Jackson G. G., Paul D. A., Falk L. A., Rubenis M., Despotes J. C., Mack D., Knigge M., Emeson E. E. Human immunodeficiency virus (HIV) antigenemia (p24) in the acquired immunodeficiency syndrome (AIDS) and the effect of treatment with zidovudine (AZT). Ann Intern Med. 1988 Feb;108(2):175–180. doi: 10.7326/0003-4819-108-2-175. [DOI] [PubMed] [Google Scholar]
  69. Jaffe H. W., Sarngadharan M. G., DeVico A. L., Bruch L., Getchell J. P., Kalyanaraman V. S., Haverkos H. W., Stoneburner R. L., Gallo R. C., Curran J. W. Infection with HTLV-III/LAV and transfusion-associated acquired immunodeficiency syndrome. Serologic evidence of an association. JAMA. 1985 Aug 9;254(6):770–773. [PubMed] [Google Scholar]
  70. Kantrowitz B., Wingert P., Hager M. Preemies. Newsweek. 1988 May 16;111(20):62–67. [PubMed] [Google Scholar]
  71. Kessler H. A., Blaauw B., Spear J., Paul D. A., Falk L. A., Landay A. Diagnosis of human immunodeficiency virus infection in seronegative homosexuals presenting with an acute viral syndrome. JAMA. 1987 Sep 4;258(9):1196–1199. [PubMed] [Google Scholar]
  72. Kestens L., Melbye M., Biggar R. J., Stevens W. J., Piot P., De Muynck A., Taelman H., De Feyter M., Paluku L., Gigase P. L. Endemic African Kaposi's sarcoma is not associated with immunodeficiency. Int J Cancer. 1985 Jul 15;36(1):49–54. doi: 10.1002/ijc.2910360109. [DOI] [PubMed] [Google Scholar]
  73. Koenig R. E., Pittaluga J., Bogart M., Castro M., Nunez F., Vilorio I., Delvillar L., Calzada M., Levy J. A. Prevalence of antibodies to the human immunodeficiency virus in Dominicans and Haitians in the Dominican Republic. JAMA. 1987 Feb 6;257(5):631–634. [PubMed] [Google Scholar]
  74. Kolata G. Imminent marketing of AZT raises problems. Science. 1987 Mar 20;235(4795):1462–1463. doi: 10.1126/science.3469753. [DOI] [PubMed] [Google Scholar]
  75. Konotey-Ahulu F. I. AIDS in Africa: misinformation and disinformation. Lancet. 1987 Jul 25;2(8552):206–207. doi: 10.1016/s0140-6736(87)90777-x. [DOI] [PubMed] [Google Scholar]
  76. Koprowski H., DeFreitas E. C., Harper M. E., Sandberg-Wollheim M., Sheremata W. A., Robert-Guroff M., Saxinger C. W., Feinberg M. B., Wong-Staal F., Gallo R. C. Multiple sclerosis and human T-cell lymphotropic retroviruses. Nature. 1985 Nov 14;318(6042):154–160. doi: 10.1038/318154a0. [DOI] [PubMed] [Google Scholar]
  77. Lackner A. A., Rodriguez M. H., Bush C. E., Munn R. J., Kwang H. S., Moore P. F., Osborn K. G., Marx P. A., Gardner M. B., Lowenstine L. J. Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues. J Virol. 1988 Jun;62(6):2134–2142. doi: 10.1128/jvi.62.6.2134-2142.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Lairmore M. D., Rosadio R. H., DeMartini J. C. Ovine lentivirus lymphoid interstitial pneumonia. Rapid induction in neonatal lambs. Am J Pathol. 1986 Oct;125(1):173–181. [PMC free article] [PubMed] [Google Scholar]
  79. Lange W. R., Haertzen C. A., Hickey J. E., Snyder F. R., Dax E. M., Jaffe J. H. Nitrite inhalants: patterns of abuse in Baltimore and Washington, D.C. Am J Drug Alcohol Abuse. 1988;14(1):29–39. doi: 10.3109/00952998809001533. [DOI] [PubMed] [Google Scholar]
  80. Levy J. A. Mysteries of HIV: challenges for therapy and prevention. Nature. 1988 Jun 9;333(6173):519–522. doi: 10.1038/333519a0. [DOI] [PubMed] [Google Scholar]
  81. Ludlam C. A., Tucker J., Steel C. M., Tedder R. S., Cheingsong-Popov R., Weiss R. A., McClelland D. B., Philp I., Prescott R. J. Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII. Lancet. 1985 Aug 3;2(8449):233–236. doi: 10.1016/s0140-6736(85)90288-0. [DOI] [PubMed] [Google Scholar]
  82. Lui K. J., Darrow W. W., Rutherford G. W., 3rd A model-based estimate of the mean incubation period for AIDS in homosexual men. Science. 1988 Jun 3;240(4857):1333–1335. doi: 10.1126/science.3163848. [DOI] [PubMed] [Google Scholar]
  83. Martin G. S., Duesberg P. H. The a subunit in the RNA of transforming avian tumor viruses. I. Occurrence in different virus strains. II. Spontaneous loss resulting in nontransforming variants. Virology. 1972 Feb;47(2):494–497. doi: 10.1016/0042-6822(72)90287-5. [DOI] [PubMed] [Google Scholar]
  84. Martin M. A., Bryan T., Rasheed S., Khan A. S. Identification and cloning of endogenous retroviral sequences present in human DNA. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4892–4896. doi: 10.1073/pnas.78.8.4892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Moss A. R., Bacchetti P., Osmond D., Krampf W., Chaisson R. E., Stites D., Wilber J., Allain J. P., Carlson J. Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort. Br Med J (Clin Res Ed) 1988 Mar 12;296(6624):745–750. doi: 10.1136/bmj.296.6624.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. N'Galy B., Ryder R. W., Bila K., Mwandagalirwa K., Colebunders R. L., Francis H., Mann J. M., Quinn T. C. Human immunodeficiency virus infection among employees in an African hospital. N Engl J Med. 1988 Oct 27;319(17):1123–1127. doi: 10.1056/NEJM198810273191704. [DOI] [PubMed] [Google Scholar]
  87. Narayan O., Cork L. C. Lentiviral diseases of sheep and goats: chronic pneumonia leukoencephalomyelitis and arthritis. Rev Infect Dis. 1985 Jan-Feb;7(1):89–98. doi: 10.1093/clinids/7.1.89. [DOI] [PubMed] [Google Scholar]
  88. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  89. Pagano J. S., Huang C. H., Levine P. Absence of Epstein-Barr viral DNA in Amercian Burkitt's lymphoma. N Engl J Med. 1973 Dec 27;289(26):1395–1399. doi: 10.1056/NEJM197312272892604. [DOI] [PubMed] [Google Scholar]
  90. Pallangyo K. J., Mbaga I. M., Mugusi F., Mbena E., Mhalu F. S., Bredberg U., Biberfeld G. Clinical case definition of AIDS in African adults. Lancet. 1987 Oct 24;2(8565):972–972. doi: 10.1016/s0140-6736(87)91456-5. [DOI] [PubMed] [Google Scholar]
  91. Paul D. A., Falk L. A., Kessler H. A., Chase R. M., Blaauw B., Chudwin D. S., Landay A. L. Correlation of serum HIV antigen and antibody with clinical status in HIV-infected patients. J Med Virol. 1987 Aug;22(4):357–363. doi: 10.1002/jmv.1890220408. [DOI] [PubMed] [Google Scholar]
  92. Pedersen C., Nielsen C. M., Vestergaard B. F., Gerstoft J., Krogsgaard K., Nielsen J. O. Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection. Br Med J (Clin Res Ed) 1987 Sep 5;295(6598):567–569. doi: 10.1136/bmj.295.6598.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Perryman L. E., O'Rourke K. I., McGuire T. C. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J Virol. 1988 Aug;62(8):3073–3076. doi: 10.1128/jvi.62.8.3073-3076.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Peterman T. A., Stoneburner R. L., Allen J. R., Jaffe H. W., Curran J. W. Risk of human immunodeficiency virus transmission from heterosexual adults with transfusion-associated infections. JAMA. 1988 Jan 1;259(1):55–58. [PubMed] [Google Scholar]
  95. Pifer L. L. Pneumocystis carinii: a misunderstood opportunist. Eur J Clin Microbiol. 1984 Jun;3(3):169–173. doi: 10.1007/BF02014871. [DOI] [PubMed] [Google Scholar]
  96. Popovic M., Gartner S. Isolation of HIV-1 from monocytes but not T lymphocytes. Lancet. 1987 Oct 17;2(8564):916–916. doi: 10.1016/s0140-6736(87)91403-6. [DOI] [PubMed] [Google Scholar]
  97. Preston B. D., Poiesz B. J., Loeb L. A. Fidelity of HIV-1 reverse transcriptase. Science. 1988 Nov 25;242(4882):1168–1171. doi: 10.1126/science.2460924. [DOI] [PubMed] [Google Scholar]
  98. RUBIN H., TEMIN H. M. A radiological study of cell-virus interaction in the Rous sarcoma. Virology. 1959 Jan;7(1):75–91. doi: 10.1016/0042-6822(59)90178-3. [DOI] [PubMed] [Google Scholar]
  99. Ranki A., Valle S. L., Krohn M., Antonen J., Allain J. P., Leuther M., Franchini G., Krohn K. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet. 1987 Sep 12;2(8559):589–593. doi: 10.1016/s0140-6736(87)92985-0. [DOI] [PubMed] [Google Scholar]
  100. Raymond C. A. Combating a deadly combination: intravenous drug abuse, acquired immunodeficiency syndrome. JAMA. 1988 Jan 15;259(3):329–332. [PubMed] [Google Scholar]
  101. Rees M. The sombre view of AIDS. 1987 Mar 26-Apr 1Nature. 326(6111):343–345. doi: 10.1038/326343a0. [DOI] [PubMed] [Google Scholar]
  102. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  103. Richman D. D., McCutchan J. A., Spector S. A. Detecting human immunodeficiency virus RNA in peripheral blood mononuclear cells by nucleic acid hybridization. J Infect Dis. 1987 Nov;156(5):823–827. doi: 10.1093/infdis/156.5.823. [DOI] [PubMed] [Google Scholar]
  104. Robey W. G., Arthur L. O., Matthews T. J., Langlois A., Copeland T. D., Lerche N. W., Oroszlan S., Bolognesi D. P., Gilden R. V., Fischinger P. J. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7023–7027. doi: 10.1073/pnas.83.18.7023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  106. Rubin H. Etiology of AIDS. Science. 1988 Jun 10;240(4858):1389–1390. [PubMed] [Google Scholar]
  107. Rubin H. Is HIV the causative factor in AIDS? Nature. 1988 Jul 21;334(6179):201–201. doi: 10.1038/334201a0. [DOI] [PubMed] [Google Scholar]
  108. Rusche J. R., Lynn D. L., Robert-Guroff M., Langlois A. J., Lyerly H. K., Carson H., Krohn K., Ranki A., Gallo R. C., Bolognesi D. P. Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6924–6928. doi: 10.1073/pnas.84.19.6924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  109. Salahuddin S. Z., Nakamura S., Biberfeld P., Kaplan M. H., Markham P. D., Larsson L., Gallo R. C. Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro. Science. 1988 Oct 21;242(4877):430–433. doi: 10.1126/science.2459779. [DOI] [PubMed] [Google Scholar]
  110. Salahuddin S. Z., Rose R. M., Groopman J. E., Markham P. D., Gallo R. C. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed] [Google Scholar]
  111. Sattentau Q. J., Weiss R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988 Mar 11;52(5):631–633. doi: 10.1016/0092-8674(88)90397-2. [DOI] [PubMed] [Google Scholar]
  112. Seligmann M., Chess L., Fahey J. L., Fauci A. S., Lachmann P. J., L'Age-Stehr J., Ngu J., Pinching A. J., Rosen F. S., Spira T. J. AIDS--an immunologic reevaluation. N Engl J Med. 1984 Nov 15;311(20):1286–1292. doi: 10.1056/NEJM198411153112005. [DOI] [PubMed] [Google Scholar]
  113. Seligmann M., Pinching A. J., Rosen F. S., Fahey J. L., Khaitov R. M., Klatzmann D., Koenig S., Luo N., Ngu J., Riethmüller G. Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update. Ann Intern Med. 1987 Aug;107(2):234–242. doi: 10.7326/0003-4819-107-2-234. [DOI] [PubMed] [Google Scholar]
  114. Selik R. M., Starcher E. T., Curran J. W. Opportunistic diseases reported in AIDS patients: frequencies, associations, and trends. AIDS. 1987 Sep;1(3):175–182. [PubMed] [Google Scholar]
  115. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  116. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  117. Stewart G. J., Tyler J. P., Cunningham A. L., Barr J. A., Driscoll G. L., Gold J., Lamont B. J. Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor. Lancet. 1985 Sep 14;2(8455):581–585. doi: 10.1016/s0140-6736(85)90585-9. [DOI] [PubMed] [Google Scholar]
  118. Stewart G. T. Limitations of the germ theory. Lancet. 1968 May 18;1(7551):1077–1081. doi: 10.1016/s0140-6736(68)91425-6. [DOI] [PubMed] [Google Scholar]
  119. Stoler M. H., Eskin T. A., Benn S., Angerer R. C., Angerer L. M. Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. JAMA. 1986 Nov 7;256(17):2360–2364. [PubMed] [Google Scholar]
  120. Stoneburner R. L., Des Jarlais D. C., Benezra D., Gorelkin L., Sotheran J. L., Friedman S. R., Schultz S., Marmor M., Mildvan D., Maslansky R. A larger spectrum of severe HIV-1--related disease in intravenous drug users in New York City. Science. 1988 Nov 11;242(4880):916–919. doi: 10.1126/science.3187532. [DOI] [PubMed] [Google Scholar]
  121. Stricker R. B., McHugh T. M., Moody D. J., Morrow W. J., Stites D. P., Shuman M. A., Levy J. A. An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells. 1987 Jun 25-Jul 1Nature. 327(6124):710–713. doi: 10.1038/327710a0. [DOI] [PubMed] [Google Scholar]
  122. Sullivan J. L., Brewster F. E., Brettler D. B., Forsberg A. D., Cheeseman S. H., Byron K. S., Baker S. M., Willitts D. L., Lew R. A., Levine P. H. Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses. J Pediatr. 1986 Apr;108(4):504–510. doi: 10.1016/s0022-3476(86)80823-x. [DOI] [PubMed] [Google Scholar]
  123. Takeuchi Y., Nagumo T., Hoshino H. Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus. J Virol. 1988 Oct;62(10):3900–3902. doi: 10.1128/jvi.62.10.3900-3902.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Temin H. M. Evolution of cancer genes as a mutation-driven process. Cancer Res. 1988 Apr 1;48(7):1697–1701. [PubMed] [Google Scholar]
  125. The cause of AIDS. Science. 1988 Nov 18;242(4881):997–998. [PubMed] [Google Scholar]
  126. Tinker J. AIDS in the developing countries. Issues Sci Technol. 1988 Winter;4(2):43–48. [PubMed] [Google Scholar]
  127. Vogt P. K. Avian tumor viruses. Adv Virus Res. 1965;11:293–385. doi: 10.1016/s0065-3527(08)60549-7. [DOI] [PubMed] [Google Scholar]
  128. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  129. Wang L., Galehouse D., Mellon P., Duesberg P., Mason W. S., Vogt P. K. Mapping oligonucleotides of Rous sarcoma virus RNA that segregate with polymerase and group-specific antigen markers in recombinants. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3952–3956. doi: 10.1073/pnas.73.11.3952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Ward J. W., Holmberg S. D., Allen J. R., Cohn D. L., Critchley S. E., Kleinman S. H., Lenes B. A., Ravenholt O., Davis J. R., Quinn M. G. Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody. N Engl J Med. 1988 Feb 25;318(8):473–478. doi: 10.1056/NEJM198802253180803. [DOI] [PubMed] [Google Scholar]
  131. Ward R. Mainstream scientists confront unorthodox view of AIDS. Nature. 1988 Apr 14;332(6165):574–574. doi: 10.1038/332574a0. [DOI] [PubMed] [Google Scholar]
  132. Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]
  133. Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]
  134. Weiss R. A. Foamy retroviruses. A virus in search of a disease. Nature. 1988 Jun 9;333(6173):497–498. doi: 10.1038/333497a0. [DOI] [PubMed] [Google Scholar]
  135. Weiss S. H., Goedert J. J., Gartner S., Popovic M., Waters D., Markham P., di Marzo Veronese F., Gail M. H., Barkley W. E., Gibbons J. Risk of human immunodeficiency virus (HIV-1) infection among laboratory workers. Science. 1988 Jan 1;239(4835):68–71. doi: 10.1126/science.3336776. [DOI] [PubMed] [Google Scholar]
  136. Wittek A. E., Phelan M. A., Wells M. A., Vujcic L. K., Epstein J. S., Lane H. C., Quinnan G. V., Jr Detection of human immunodeficiency virus core protein in plasma by enzyme immunoassay. Association of antigenemia with symptomatic disease and T-helper cell depletion. Ann Intern Med. 1987 Sep;107(3):286–292. doi: 10.7326/0003-4819-107-2-286. [DOI] [PubMed] [Google Scholar]
  137. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]
  138. de Wolf F., Goudsmit J., Paul D. A., Lange J. M., Hooijkaas C., Schellekens P., Coutinho R. A., van der Noordaa J. Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia. Br Med J (Clin Res Ed) 1987 Sep 5;295(6598):569–572. doi: 10.1136/bmj.295.6598.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  139. von Briesen H., Becker W. B., Henco K., Helm E. B., Gelderblom H. R., Brede H. D., Rübsamen-Waigmann H. Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. J Med Virol. 1987 Sep;23(1):51–66. doi: 10.1002/jmv.1890230107. [DOI] [PubMed] [Google Scholar]

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