HIV/AIDS

1. HIV/AIDS Donna Sullivan, PhD Division of Infectious Diseases University of Mississippi Medical Center

4. DENDRITIC CELLS, MACROPHAGES, AND HIVNEJM 340:1732

5. HIV-1 LIFE CYCLE Nature Insight. Nature 410, 965 (01). Used with permission.

8. THE GENOME OF THE HUMAN IMMUNODEFICIENCY VIRUS (TYPE 1)

15. HIV DIAGNOSTIC TESTING • Enzyme linked Immunosorbent Assay (ELISA) • Sensitivity and specificity ar >98% • Confirmatory testing • Western blot, IFA (specificity >99%) • Home Testing/Rapid Testing • Salivary antibodies • Finger stick whole blood

16. An ELISA plate

17. ELISA Activity: ELISA data from three patients

18. Western Blot Analysis Band pattern Interpretation Lane 1, HIV+ serum (positive control) Lane 2, HIV- serum (negative control) Lane A, Patient A Lane B, Patient B Lane C, Patient C

19. Band Pattern Interpretation • No bands present Negative • Bands at either p31 OR Positive p24 AND bands present at either gp160 OR gp120 • Bands present, but pattern Indeterminate does not meet criteria for positivity

20. WHEN TO MEASURE HIV RNA AND CD4+ T CELL LEVELS • Syndrome consistent with acute HIV infection • Initial evaluation of new HIV diagnosis • Every 3-4 months in untreated patient • Immediately prior to initiating therapy • 2-8 weeks after initiating therapy • Every 3-4 months in patients on therapy

22. PLASMA HIV RNA - VIRAL LOAD • The number of HIV RNA strands in the plasma or serum of an HIV-infected persons • measured in logs (10,000 low risk, 100,000 high risk of progression to AIDS) • detectable after about 1-2 weeks at about 500 copies

23. CHARACTERISTICS OF PLASMA HIV RNA ASSAYS

26. AIDS DEFINING CONDITIONS (CDC) • HIV + test with: • CD4 lymphocyte count <200/mm3 OR • Opportunistic Infections • Oropharyngeal candidiasis • Pneumocystis carinii pneumonia (PCP) • Disseminated cryptococcal infection • CMV disease (retinitis) • Progressive multifocal leukoencephalopathy • Mycobacterium avium complex, disseminated

27. 1. Viral attachment to CD4 of Helper T cells. 2. Attachment to co-receptor CXCR4 or CCR5. 3. Uncoating. 4. Reverse transcription of viral RNA to form DNA. 5. Synthesis of second strand of DNA. 6. Migration to the nucleus. 7. Integration and transcription of viral DNA. 8. Translation of viral RNA. 9. Viral protease enzyme activation, a site for protease inhibitors to block viral replication. 10. Assembly and budding to form new virus HIV Has Multiple Steps Available for Attack by Antiretroviral Drugs

28. HAART THERAPY • Highly Active Anti-Retroviral Therapy • Combination of drugs • RT inhibitors (nucleoside analogs, non-nucleoside analogs) • Protease inhibitors • Given when patients CD4+ cells drop below 200

29. ANTIRETROVIRAL DRUGS • Ritonavir (Norvir) • Saquinivir (Invirase) • Indinavir (Crixivan) • Amprenivir (Agenerase) • Nelfinavir (Viracept) • Lopinavir (Kaletra)

31. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) • Zidovudine (AZT, Retrovir) • Lamivudine (3TC, Epivir) • Didanosine (ddI, Videx EC) • Stavudine (d4T, Zerit) • Abacavir (Ziagen) • Tenofovir (Viread) nucleotide analog • Emtricitabine (Coviracil)

32. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) • Delavirdine (Rescriptor) • Efavirenz (Sustiva) • Nevirapine (Viramune)

33. PROTEASE INHIBITORS • Nelfinavir (Viracept) • Indinavir (Crixivan) • Saquinair (Fortovase, Invirase) • Ritonavir (Norvir) • Lopinavir/ritonavir (Kaletra) • Amprenavir (Agenerase) • Fosamprenavir (?) • Atazanavir (Rayataz)

34. Column A Efavirenz Indinavir Nelfinavir Ritonavir+ Indinavir Ritonavir + Lopinavir* Ritonavir + Saquinavir Column B Didanosine + Lamivudine Stavudine + Didanosine Stavudine + Lamivudine Zidovudine + Didanosine Zodovudine + Lamivudine *Coformulated as Kaletra INITIAL TREATMENT: One Choice from Each Column

35. INDICATIONS FOR INITIATION OF THERAPY: Chronic Infection

36. INDICATIONS FOR INITIATION OF THERAPY: Chronic Infection

38. Estimated proportion of persons surviving, by months after AIDS diagnosis during 1994–2001 and by year of diagnosis—United States

39. BACTERIA M. tuberculosis M. avium complex S. pneumococcus M. catarrhalis H. influenza P. aeruginosa Nocardia Legionella pneumophila FUNGI Pneumocystis carinii Cryptococcus neoformans Histoplasma capsulatum Coccidiodes immitis Aspergillus fumigatus Penicillium marneffei Candida albicans PULMONARY INFECTIONS

40. VIRUSES Cytomegalovirus Herpes simplex Adenovirus HIV Lymphocytic interstitial pneumonitis (in children) PROTOZOANS Toxoplasma gondii Cryptosporidium Microsporidia TUMORS Kaposi’s sarcoma (HHV8) Non-Hodgkin’s lymphoma PULMONARY INFECTIONS

41. Pneumocystis carinii in Lung

42. Pneumocystis carinii Pneumonia: Cavitary Change

43. Gomori Methenamine Silver Stain at High Magnification: P. carinii

44. TB IN AIDS PATIENTS: AFRICA

45. CMV Inclusions in Lung

46. Candida albicans Invasive Process in a Bronchus with H and E Staining

47. C neoformans: Clear capsule surrounding the pale blue nucleus with H and E staining

48. Histoplasma capsulatum

49. Histoplasma capsulatum organisms in macrophages in liver with PAS stain

50. INFECTIONS T. gondii PML (JC virus) M. tuberculosis C. neoformans CMV HSV-1 HIV Candida albicans NEOPLASMS Primary CNS lymphoma Metastatic Lymphoma Kaposi’s sarcoma UNIDENTIFIED Aseptic meningitis Non-specific gliosis Vascular myelopathy CNS/NEUROLOGIC COMPLICATIONS