HIV-1 & HIV : Robert Gallo: HTLV-1/ lymphocytes 1978: Robert Gallo: HTLV-1/ lymphocytes of leukemia patients of leukemia patients HTLV : 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

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)

HIV and AIDS Clusters of infected men Apparent concentration within sexually interactive groups High numbers of sex partners Distinguishing characteristics Suggests an infectious agent

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

Obvious agent: A virus……that is now in the blood supply Primary route of transmission: Sex AIDS is a sexually-transmitted viral disease

PROPERTIES Classification Retroviridae Retroviridae Reverse transcriptase (RT) Reverse transcriptase (RT) Morphology Icosahedral, 100 nm Icosahedral, 100 nm Enveloped Enveloped

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

Replication of retrovirus

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.

The clinical manifestation: Malignant disease:.Kaposi`s sarcoma, common.B-cell lymphoma.Non-Hodgkins lymphoma.Genital cancers Infective manifestations:.Many opportunistic infections

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

PATHOGENESIS Transmission

IMMUNE RESPONSE p24 Ags appear at early stage of infection followed by Ab to gp120 + gp41 then Abs to p24

The time course of development of HIV antigens and antibodies

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)

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 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

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%

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