HIV/AIDS M3 lecture

1. HIV/AIDS M3 lecture Angela Remington, MD MS Fellow Infectious Diseases Updated 2005

2. Introduction • AIDS first recognized 1981 • HIV RNA retrovirus discovered 1983 • 2nd leading cause of disease burden worldwide • Leading cause of death in Africa • Approx 1 million people currently diagnosed in America

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. AIDS • CD4 <200 • Pneumocystis pneumonia • Esophageal Candidiasis • Mucocutaneous herpes simplex • Miliary/extrapulmonary TB • Cryptosporidium • HIV-associated wasting • Microsporidium • Peripheral neuropathy

15. AIDS • CD <100 • Cerebral toxoplasmosis • Non-Hodgkin’s lymphoma • Cryptococcal meningitis • HIV-associated dementia • Primary CNS Lymphoma • Progressive multifocal leukoencephalopathy

16. AIDS • CD4<50 • CMV retinitis, gastroenteritis • Disseminated Mycobacterium avium complex

17. Diagnosis • Antibody test, ELISA • Western blot • HIV RNA viral load

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

22. GI disease • Esophageal candidiasis • Large bowel disease (bloody diarrhea) • C. diff • CMV • Small bowel disease (watery diarrhea) • Cryptosporidium • Microsporidium • Giardia • MAC • CMV

23. Pulmonary Disease • Pneumocystis pneumonia • Bacterial pneumonia • Nocardia

24. 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

25. 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

26. Nervous system disease • Toxo • Crypto • PML • CMV retinitis • Dementia • Peripheral neuropathy

27. Management • Treatment recommended when symptomatic or CD4 count below 200 • Earlier if high viral load, rapidly falling CD4 count, hepatitis C co-infection

28. antiretrovirals • Nucleoside reverse transcriptase inhibitors • Non-nucleoside reverse transcriptase inhibitors • Protease inhibitors • Fusion inhibitors • R5/X4 inhibitors

29. NRTIs • ddC • ddI • 3TC • ZDV • d4T • Abacavir • FTC

30. NNRTIs • Nevirapine • Efavirenz • Delavirdine

31. PIs • Indinavir • Saquinavir • Ritonavir • Nelfinavir • Lopinavir/ritonavir • Amprenavir • Fosamprenavir • Tipranavir • Atazanavir

32. Others • T-20 • Tenofovir • R5/X4 under development

33. 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