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  1. 1. HIV/AIDS M3 lecture Angela de padre, MDYashar Najiaghdam, MDFellow Infectious Diseases Updated 2011-2012
  2. 2. Introduction AIDS first recognized 1981 HIV RNA retrovirus discovered 1983 2ndleading cause of disease burden worldwide Leading cause of death in Africa Approx 1 million people currently diagnosed in America
  3. 3. Transmission of HIV Blood, semen, breast milk, saliva Sexual, parenteral, vertical Risk of contracting infection dependent on – Viral load – Integrity of the exposed site – Type of body fluid – Volume of body fluid
  4. 4. Transmission of HIV Risk after a single exposure – >90% blood or blood products – 14% vertical – 0.5-1% injection drug use – 0.2-0.5% genital mucous membrane – <0.1% non-genital mucous membrane
  5. 5. MTCT of HIV Developing countries 40% On Zidovudine alone 7% Zidovudine with C-section 2% HAART <1% if viral load <50 copies 80% of those infected vertically are infected close to the time of delivery
  6. 6. Transmission Risk of transmission is now 1/10,000,000 with each unit of blood 100 confirmed cases from healthcare exposure Risk with needle stick 0.32% Risk with mucous membrane exposure 0.03%
  7. 7. global Estimated 42 million people living with HIV/AIDS in 2002 5 million new infections per year 3 million deaths per year Parts of Africa 25-40% of adults are infected 85% heterosexual transmission worldwide
  8. 8. The Virus Glycoproteins (gp 120, gp41) 2 copies of ssRNA, viral enzymes Attachment with gp 120 to CD4 receptor Fusion mediated by gp 41 Inside cell RNA transcribed to DNA by RT DNA incorporated into cell genome DNA is copied and translated to viral enzymes, proteases New infectious virus buds from host cell to repeat process
  9. 9. Immunology Gradual reduction in number of circulating CD4 cells inversely correlated with the viral load Any depletion in numbers of CD4 cells renders the body susceptible to opportunistic infections Lymphatic tissue (spleen, lymph nodes, tonsils/adenoids) main reservoir of HIV
  10. 10. Primary Infection 70-80% symptomatic, 3-12 weeks after exposure Fever, rash, cervical lymphadenopathy, aseptic meningitis, encephalitis, myelitis, polyneuritis Surge in viral RNA copies to >1 million Fall in CD4 count to 300-400 Recovery in 7-14 days
  11. 11. Seroconversion 3-12 weeks, median 8 weeks Level of viral load post seroconversion correlates with risk of progression of disease Differential for this syndrome: EBV, CMV, Strep pharyngitis, toxoplasmosis, secondary syphilis
  12. 12. Asymptomatic phase Remain well with no evidence of HIV disease except for generalized lymphadenopathy Fall of CD4 count by about 50-150 cells per year
  13. 13. Symptomatic phase Mild impairment of immune system Chronic weight loss Fever Diarrhea Mild candida infections Recurrent herpes infections Pelvic inflammatory disease Bacillary angiomatosis Cervical dysplasia
  14. 14. AIDS CD4 <200 – Pneumocystis pneumonia – Esophageal Candidiasis – Mucocutaneous herpes simplex – Miliary/extrapulmonary TB – Cryptosporidium – HIV-associated wasting – Microsporidium – Peripheral neuropathy
  15. 15. AIDS CD <100 – Cerebral toxoplasmosis – Non-Hodgkin’s lymphoma – Cryptococcal meningitis – HIV-associated dementia – Primary CNS Lymphoma – Progressive multifocal leukoencephalopathy
  16. 16. AIDS CD4<50 – CMV retinitis, gastroenteritis – Disseminated Mycobacterium avium complex
  17. 17. Diagnosis Antibody test, ELISA Western blot HIV RNA viral load
  18. 18. Skin and Oral disease Seborrheic dermatitis Xeroderma Itchy folliculitis Scabies Tinea Herpes zoster Papillomavirus Oral and vaginal candidiasis Oral hairy leukoplakia Aphthous ulcers Herpes simplex Gingivitis Kaposi’s sarcoma Molluscum contagiosum Bacillary angiomatosis
  19. 19. GI disease Esophageal candidiasis Large bowel disease (bloody diarrhea) – C. diff – CMV Small bowel disease (watery diarrhea) – Cryptosporidium – Microsporidium – Giardia – MAC – CMV
  20. 20. Pulmonary Disease Pneumocystis pneumonia Bacterial pneumonia Nocardia
  21. 21. Pneumocystis pneumonia Most common AIDS presenting illness Reactivation of infection (original airborne transmission, asymptomatic, early age) Inversely correlated with CD4 count 40% of patients with CD4 <100 and not prophalaxed will have pneumonia annually Prophalaxis started at CD4 <200, trimethoprim/sulfa, dapsone, atovaquone, pentamidine
  22. 22. Pneumocystis pneumonia 2-3 week history of SOB and dry cough Hypoxemia Perihilar ground glass appearance on CXR Silver stain of organism in sputum High dose trimethaprim/sulfa, steroid if hypoxic
  23. 23. Nervous system disease Toxo Crypto PML CMV retinitis Dementia Peripheral neuropathy
  24. 24. Management Treatment recommended when symptomatic or CD4 count below 200 Earlier if high viral load, rapidly falling CD4 count, hepatitis C co-infection
  25. 25. antiretrovirals Nucleoside reverse transcriptase inhibitors Non-nucleoside reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors R5/X4 inhibitors
  26. 26. NRTIs ddC ddI 3TC ZDV d4T Abacavir FTC
  27. 27. NNRTIs Nevirapine Efavirenz Delavirdine
  28. 28. PIs Indinavir Saquinavir Ritonavir Nelfinavir Lopinavir/ritonavir Amprenavir Fosamprenavir Tipranavir Atazanavir
  29. 29. Others T-20 Tenofovir R5/X4 under development
  30. 30. Side effects NRTIs: mitochondrial dysfunction ddC, ddI, d4T: neuropathy d4T, ddI: hepatic steatosis, lactic acidosis ddI: pancreatitis ZDV: anemia d4T: fat atrophy Abacavir: hypersensitivity reaction Tenofovir: renal failure NNRTIs: rash, liver toxicity PIs: fat redistribution, insulin resistance, hyperlipidemia Indiavir: renal stones Nelfinavir: diarrhea