HIV INFECTION AND THE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

1. HIV INFECTIONAND THE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

2. 1981 1982 1983 1984 1986 Recognition of Pneumocystis carinii pneumonia (PCP) and Kaposi’s sarcoma (KS) in young healthy men in NYC and Los Angeles GRID to AIDS by CDC Isolation of Lymphadenopathy-Associated Virus (LAV) by Pasteur Institute (Luc Montagnier) Isolation of Human T-Lymphotrophic Virus , Type III (HTLV-III) by NCI/NIH (Robert Gallo) Recommendation of the name Human Immunodeficiency Virus (HIV) by an international subcommittee on virus taxonomy HISTORICAL PERSPECTIVES OF AIDS

7. HUMAN IMMUNODEFICIENCY VIRUSES (HIV) • Classification • Retroviridae (family) • Lentivirus (genus) • Characteristics • 100 nm in diameter • Genome of 2 single strands of RNA • Nine genes • Reverse transcriptase • RNA-dependent DNA polymerase • Transcribes RNA into DNA

11. GENOME OF HIV • Contains 6 regulatory genes • Contains 3 structural genes • Env (Envelope glycoproteins) • gp120 and gp41 • Gag (Core and matrix proteins) • p55, p40 and p24 • Pol (Enzymes) • Reverse transcriptase (p66, p51) • Protease (p11) • Integrase (p32)

13. HUMAN RETROVIRIDAE (EXOGENOUS RETROVIRUSES) • Seven genera • Alpha, Beta, Gamma, Delta, Epsilon, Lenti and Spuma • Deltavirus • Human T-lymphotropic virus, type I (HTLV-1) • Human T-lymphotropic virus, type II (HTLV-II) • Lentivirus • Human immunodeficiency virus, type 1 (HIV-1) • Human immunodeficiency virus, type 2 (HIV-2)

14. CLASSIFICATION OF THE HUMAN IMMUNODEFICIENCY VIRUSES (HIV) • Types • Human immunodeficiency virus, type 1 (HIV-1) • Human immunodeficiency virus, type 2 (HIV-2) • HIV-1 is divided into groups • M (Major) • N (New) • O (Outlier) • Group M is divided into • Subtypes (Clades) • Circulating recombinant forms (CRF)

15. CLASSIFICATION OF HIV

16. ORIGIN OF HUMAN IMMUNODEFICIENCY VIRUSES • Existed as monkey virus in equatorial Africa • HIV-1 • Chimpanzee (Pan troglodytes troglodytes) • HIV-2 • Sooty Mangabey (Cercocebus atys) • Transition from monkeys to humans • When - Circa 1908 • Molecular phylogenetics • How – Hunter theory

19. MECHANISM OF PATHOGENICITY OF HIV • Envelope protein (gp120) of HIV binds with CD-4 receptor on surface of • T-lymphocytes • Macrophages • Dendritic cells • Microglial cells • Coreceptors for attachment of HIV • CCR5 (T-cells, macrophages, dendritic cells, microglial cells) • CXCR4 (T-cells)

20. MECHANISM OF PATHOGENICITY OF HIV • Early infection • CCR5 coreceptor is used (R5 strains) • Growth equal in monocytes and lymphocytes • Non syncytium-inducing (NSI) • Late infection • CXCR4 coreceptor is used (X4 strains) • Growth in T cells • Syncytium-inducing (SI) • Emergence of X4 strains associated with accelerated decline in CD4 T cells • Cause or consequence?

21. MECHANISM OF PATHOGENICITY OF HIV • Following attachment, virus enters cells and removes protein coat • Viral RNA is transcribed into DNA by • Reverse transcriptase • Viral DNA then integrated into host cell DNA • Integrase • Integrated viral DNA • Referred to as “provirus” • Production of active infection

24. EPIDEMIOLOGY OF HIV INFECTION AND AIDS • Since 1981, 65 million people worldwide have contracted HIV • > 25 million deaths • 87% of HIV cases in developing nations • 64% in sub-Saharan Africa • 23% in southern and Southeast Asia • Since 1981, 1.5 million people in the U.S. have contracted HIV • Approximately 576,000 deaths • In 2009, 56K new cases in the U.S.

27. TRANSMISSION OF HIV INFECTION AND AIDS • Sexual intercourse with infected person • Homosexual (MSM) • Heterosexual • Bisexual • Children born to infected mothers • Perinatal • IV drug addicts sharing contaminated syringes/needles • Transfusion of blood and blood products • Transfusion recipients • Hemophiliacs • Occupational exposure in health-care setting

28. CDC CLASSIFICATION OF HIV INFECTION AND DISEASE IN ADULTS AND ADOLESCENTS • Latest revision in 1993 • Clinical Categories • A • B • C • CD4 T Cell Categories (Absolute number or %) • > 500/uL or > 29% of total lymphocytes • 200 – 499/uL or 14-28% of total lymphocytes • < 200/uL or < 14% of total lymphocytes

29. CDC CLASSIFICATION SYSTEM

32. CDC CLASSIFICATION SYSTEM(CLINICAL CATEGORY A) • Following initial infection • Asymptomatic • Acute Retroviral Syndrome • Infectious mononucleosis-like or flu-like illness • 2 days to 4 weeks following infection • Clinical manifestations • Fever, headache, lethargy, pharyngitis, myalgias, photophobia, lymphadenopathy and a faint maculopapular rash • Resolution within 30 days • Persistent generalized lymphadenopathy (PGL)

35. CDC CLASSIFICATION SYSTEM (CLINICAL CATEGORY B) • Symptomatic conditions not meeting conditions of clinical categories A or C • Herpes zoster (shingles) • Oropharyngeal Candidiasis (thrush) • Candida albicans • Vulvovaginal candidiasis • Bacillary angiomatosis • Bartonella henselae • Peripheral neuropathy • Idiopathic thrombocytopenic purpura (ITP) • Hairy leukoplakia (oral)

40. CDC CLASSIFICATION SYSTEM (CLINICAL CATEGORY C) • Acquired Immunodeficiency Syndrome (AIDS) Defining Conditions • Esophageal Candidiasis • Cryptosporidiosis • Pneumocystis jiroveci (carinii) pneumonia • Tuberculosis (pulmonary or extrapulmonary) • Disseminated Mycobacterium avium complex (MAC) disease • Histoplasmosis (disseminated or extrapulmonary)

41. HIV INFECTION IN ADULTS (CLINICAL CATEGORY C) • Acquired Immunodeficiency Syndrome (AIDS) Defining Conditions • HIV wasting syndrome • Cryptococcal meningitis • Cytomegalovirus retinitis • Cerebral Toxoplasmosis • Progressive multifocal leukoencephalopathy (PML) • JC virus • Kaposi’s sarcoma • Human herpesvirus type 8 (HHV-8)