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HIV-1 & HIV-2 1978: Robert Gallo: HTLV-1/ lymphocytes 1978: Robert Gallo: HTLV-1/ lymphocytes of leukemia patients of leukemia patients HTLV-2 1981: AIDS: 1981: AIDS:. Homosexual male:. Pneumocystic carinii. Kaposi`s sarcoma. Kaposi`s sarcoma. 1983: Montagnier & Barre-Sinoussi/Pasteur Institute Institute. Isolate HIV-1 (Confirmed by Robert Gallo/USA). HIV-2 / Africa
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HIV and AIDS Two rare diseases in the gay community linked toIMMUNOSUPPRESSION OPPORTUNISTIC INFECTIONS Also Lymphadenopathy Gay-Related Immune Deficiency Acquired Immune Deficiency Syndrome (AIDS)
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HIV and AIDS Clusters of infected men Apparent concentration within sexually interactive groups High numbers of sex partners Distinguishing characteristics Suggests an infectious agent
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Female sex partners of AIDS-positive IV drug users and hemophiliacs Not just in the Gay community More evidence for an infectious agent Different ways of getting a similar syndrome Blood transfusions Intravenous drug use Hemophilia (clotting factor) HIV and AIDS
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Obvious agent: A virus……that is now in the blood supply Primary route of transmission: Sex AIDS is a sexually-transmitted viral disease
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PROPERTIES Classification Retroviridae Retroviridae Reverse transcriptase (RT) Reverse transcriptase (RT) Morphology Icosahedral, 100 nm Icosahedral, 100 nm Enveloped Enveloped
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Genome +ssRNA (2 copies) +ssRNA (2 copies) Several copies of RT, integrase, proteases Several copies of RT, integrase, proteases env gene : gp120 + gp41(gp160) env gene : gp120 + gp41(gp160) gag = : p24 gag = : p24 pol = : RT, integrase, protease pol = : RT, integrase, protease
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Replication of retrovirus
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CLINICAL ASPECTS IP: 3-4 W IP: 3-4 W Stage A: Influenza-like illness: 60% of infected Stage A: Influenza-like illness: 60% of infected individual move to individual move to Stage B:AIDS-related complex: =4 years, fever, Stage B:AIDS-related complex: =4 years, fever, weight loss, persistent lymphadenopathy, night sweats, and weight loss, persistent lymphadenopathy, night sweats, anddiarrhea Stage C:Full-blown AIDS: Thrush, herpes zoster, Stage C:Full-blown AIDS: Thrush, herpes zoster, Pneumocystis carinii pneumonia Time: Start Death : 10 years (70%), rest: 17 years; Long- term survivors or non- Time: Start Death : 10 years (70%), rest: 17 years; Long- term survivors or non- progressor`s group.
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The clinical manifestation: Malignant disease:.Kaposi`s sarcoma, common.B-cell lymphoma.Non-Hodgkins lymphoma.Genital cancers Infective manifestations:.Many opportunistic infections
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Neurological sequelae Involve CNS: Loss of memory & balance Aids in children: Infected by: -Transplantation - During delivery, blood contact -Breast milk * Azidothymidine (AZT) to pregnant women: Reduce the transmission
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PATHOGENESIS Transmission
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IMMUNE RESPONSE p24 Ags appear at early stage of infection followed by Ab to gp120 + gp41 then Abs to p24
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The time course of development of HIV antigens and antibodies
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EPIDEMIOLOGY * 1 (Infected reported case) 10 * 1 (Infected reported case) 10 (Infected not reported) 100 (Carrier) (Infected not reported) 100 (Carrier) * Two distinct genetic variation: - M (Major): 8 genetic subtypes (A-H). B subtypes: Europe & USA (Homosexual) (Homosexual). C & E: Africa (Heterosexual) - Out-lier (O)
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Approximately 44,000,000 people in the world are HIV- infected Approximately 14,000 new HIV infections occur daily around the world Over 90% of these are in developing countries 1000 are in children less than 15 years of age. Of adult infections, 48% are in women and 15% in individuals 15-25 years As of December 2003, 929,985 Americans reported with AIDS. At least 501,669 of them have died (2002 figures) 5,315 children under 15 AIDS Statistics
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LABORATORY DIAGNOSIS ELISA: Abs to env protein Confirmed by western blot analysis Viral genome load assay: Increase RNA copies Increase onset of AIDS New test: Saliva oVPR37 protein o20 min. oAccuracy 99%
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HIV VACCINE Inactivated whole-virus vaccine: Inactivated whole-virus vaccine: Weak immune response Recombinant DNA techniques (env gene: gp160 or gp120): Yeast & E.coli: No Recombinant DNA techniques (env gene: gp160 or gp120): Yeast & E.coli: No satisfactory protection satisfactory protection Live attenuated HIV vaccine (Mutate or alter nef gene: Increase viral replication & spread): Under investigation Live attenuated HIV vaccine (Mutate or alter nef gene: Increase viral replication & spread): Under investigation
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