AIDS: Epidemiology

1. AIDS: Epidemiology • AIDS in 2007 • Race. Blacks/African Americans account for the majority of the number of AIDS diagnoses made, followed by Whites and Hispanics/Latinos. • Region. Of the estimated 455,636 (including children) persons living with AIDS in the US: 29% Northeast, 11% Midwest, 40% South, 20% West. • Source: http://www.cdc.gov/hiv/resources/factsheets/geographic.htm#2

2. AIDS: Epidemiology • AIDS in 2007. • Blacks/African Americans accounted for the largest proportion of AIDS cases in all areas except the West where whites accounted for the highest number of cases • Source: http://www.cdc.gov/hiv/resources/factsheets/geographic.htm#2

8. Some Rapid Review for HIV/AIDS • CD4<200: start prophylaxis for what? Which drug do you use? If they have a sulfa allergy? • CD4 <100 and ring-enhancing lesions on imaging? Diagnosis? Treatment? • CD4 <50, Interstitial Pneumonia or cotton wool spots on retina w/ Owl’s-eye inclusion on biopsy: diagnosis? Treatment? Mechanism?

9. Some Rapid Review for HIV/AIDS • CD4<200: start prophylaxis for what? Which drug do you use? If they have a sulfa allergy? -PneumocystisJiroveci. Tx= TMP-SMX, Dapsone if sulfa allergy or aerosolized Pentamide if poorly tolerated. • CD4 <100 and ring-enhancing lesions on imaging? Diagnosis? -ToxoplasmaGondii . Tx= Sulfadiazine + Pyrimethamine • CD4 <50, Interstitial Pneumonia or cotton wool spots on retina w/ Owl’s-eye inclusion on biopsy: diagnosis? Treatment? Mechanism? • CMV. Tx= Ganciclovir, Foscarnet, Cidovovir. All of these inhibit viral DNA Polymerase, but Ganciclovir requires a viral kinase to become active whereas the other two do not.

10. Buzz Words: Gp120 Gp41 CCR5 CXCR4 Reverse transcriptase, integrase, protease

11. High Yield Drug info • What drug blocks gp120 attachment to CCR5? • What drug inhibits fusion and entrance of HIV into the cell by not allowing the conformational change of gp41 to take place? • Be able to recognize the NRTIs and NNRTIs- can’t help you there, just learn them! • What is our integrase inhibitor? • How do you recognize the protease inhibitors in a list?

12. High Yield Drug info • What drug blocks gp120 attachment to CCR5? -Maraviroc • What drug inhibits fusion and entrance of HIV into the cell by not allowing the conformational change of gp41 to take place? -Enfuvirtide: binds to gp41 and prevents fusion pore formation • Be able to recognize the NRTIs and NNRTIs- can’t help you there, just learn them! • What is our integrase inhibitor? -Raltegravir • How do you recognize the protease inhibitors in a list? - “Navirtease a pro tease” => all protease inhibitors end with suffix -navir

13. Replication Review • Is HIV single stranded or double stranded? • RNA or DNA virus? • How many copies of genome found within the capsid of a mature virus? • Name the 3 pre-packaged proteins that are dumped into the host cell cytoplasm upon fusion and entrance of HIV. • Gp120 attaches to what on CD4 cells? On Macrophages? • What is responsible for synthesizing viral mRNA?

14. Replication Review • Is HIV single stranded or double stranded? • RNA or DNA virus? • ssRNA virus • How many copies of genome found within the capsid of a mature virus? • 2, this is a diploid virus; 2 copies of ssRNA are found in the mature virus. • Name the 3 pre-packaged proteins that are dumped into the host cell cytoplasm upon fusion and entrance of HIV. • Reverse Transcriptase, Integrase, Protease • Gp120 attaches to what on T cells? On Macrophages? • On T cells: CCR5 or CXCR4, On Macrophages: CCR5 • What is responsible for synthesizing viral mRNA? • Host cell DNA polymerase. Reverse Transcriptase makes DNA from RNA, not the other way around.

15. HIV Pathogenesis

16. 3 Phases of HIV • Acute • Clinical latency – Establishment of chronic & persistent infection • AIDS – Advanced HIV disease

17. Acute Retroviral phase • Primary infection • Initial viremia • Dissemination of HIV • HIV-specific immune response

18. Acute Primary infection

19. Acute Initial viremia

20. AcuteDissemination

21. Acute HIV-specific immune response • Establishes chronic & persistent infection in lymphoid tissues

22. Acute Retroviral SyndromeClinical manifestations • “Mononucleosis-like” or “Flu-like” illness • Occurs in 50-70% of infected individuals • 3-6 weeks after primary infection • May or may not be sero (+)

23. Chronic Phase – Clinical Latency • Persistent viral replication • Immune system evasion • HIV-reservoir cells

24. ChronicCD4

25. ChronicMacrophages • IL-1 • Endothelial adhesion • Chemokine secretion - lymphocytes • IL-6 • APR • IL-8 • Chemotactic - neutrophils • IL-12 • T cell differentiation  Th1 • Activates NKC • TNFα • Activates endothelium • Leukocyte recruitment

26. ChronicDendritic cells • HIV reservoir

27. ChronicImmune activation-induced apoptosis

28. Natural Killer Cells • CD16 binds Fc-IgG • CD56

29. AIDS • HIV infection AND CD4 < 200/μL (cells/mm3) • AND/OR CD4 count < 14% • AND/OR AIDS-defining conditions • Opportunistic infections, unusual cancers

31. CD4 < 200/μL (cells/mm3)Pneumocystisjiroveci (carinii) • Inhaled yeast • Diffuse interstitial (atypical) pneumonia • Dx: lung bx or BAL • Methenamine silver stain: disk-shaped yeast • CXR: B/L, diffuse • Prophylaxis: • TMP/SMX • Pentamidine • Dapsone

32. CD4 < 200/μL (cells/mm3)Cryptosporidium • Ingesting oocysts in water • Severe chronic watery diarrhea (mild in immunocompetent) • Stain: acid-fast cysts • Prevention: filter city water

33. CD4 < 200/μL (cells/mm3)JC Virus • Circular non-enveloped dsDNA Polyomavirus • Progressive multifocal leukoencephalopathy • Reactivation of latent virus • Demyelination of white matter

34. CD4 < 100/μL (cells/mm3)Histoplasmacapsulatum • Dimorphic fungi: • Cold = mold • Heat = yeast • MS & OH river valleys • Bird or bat poop • Systemic: • Low-grade fever, cough, hepatosplenomegaly, tongue ulcer • Sabaroud’s agar: oval yeast cells w/in macrophages • Prophylaxis: itraconazole

35. CD4 < 100/μL (cells/mm3)Candida albicans • Dimorphic yeast • 20°C: pseudohyphae & budding yeasts • 37° C – germ tubes • Esophageal thrush (oral thrush if CD4 < 400) • Stain: branched budding & pseudohyphae • Prophylaxis: • Fluconazole • Caspofungin

36. CD4 < 100/μL (cells/mm3)Toxoplasmagondii • Protozoa • Ingest cysts in undercooked meat or cat poop • Reactivation of latent toxoplasmosis • Encephalitis, brain abscess • CT/MRI: ring-enhancing lesions • Dx: serology, bx • Prophylaxis: TMP/SMX

37. CD4 < 50/μL (cells/mm3)Cryptococcus neoformans • Heavily polysaccharide encapsulated yeast (NOT dimorphic) • Inhaled soil & pigeon poop • Meningitis (may also cause encephalitis) • India ink stain (CSF): yeasts with narrow-based budding & large halo capsule • Prophylaxis: fluconazole

38. CD4 < 50/μL (cells/mm3)Cytomegalovirus • Linear, enveloped dsDNAHerpesvirus (HHV-5) • Reactivation of latent CMV in mononuclear cells • Retinitis • Cotton-wool spots • Interstitial pneumonia • Intranuclear (owl’s eye) inclusion bodies

39. CD4 < 50/μL (cells/mm3)Mycobacterium avium – intracellulare • Acid-fast • Tuberculosis-like sx • Prophylaxis: clarithromycin or azithromycin

40. Other common diseases of AIDS • Kaposi’s sarcoma: HHV-8 • Lymphocytic inflammation • Hairy leukoplakia: EBV • Lateral tongue • Non-Hodgkin’s lymphoma: EBV • Oropharynx (Waldeyer’s ring) • Squamous cell carcinoma: HPV • Anus (MSM), cervix (females) • Primary CNS lymphoma: EBV • Focal or multiple, differentiate from toxoplasmosis