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HIV Update and State of the Art

HIV Update and State of the Art

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HIV Update and State of the Art

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  1. HIV Update and State of the Art Christian Woods, MD

  2. Disclosures • Speaker Bureau for Cubist Pharmaceuticals

  3. Objectives • Brief review of advances in HIV medicine • Brief review of the current epidemiology of HIV • Brief review of advances in HIV prevention

  4. HIV Update and State of the Art The basics

  5. Co-Receptor Inhibitors

  6. Fusion Inhibitors

  7. Nucleoside Reverse Transcriptase Inhibitors

  8. Non-Nucleoside Reverse Transcriptase Inhibitors

  9. Integrase Inhibitors

  10. Protease Inhibitors

  11. Acute HIV • Fever • Fatigue and Myalgia • Lymphadenopathy • Pharyngitis (nonexudative) • Weight Loss • Headache • Nausea & Diarrhea • Rash (erythematous, macular) • Thrush • Rarely Pneumocystis • Aseptic Meningitis

  12. CDC HIV CLASSIFICATION SYSTEM CD4 Criteria Symptom Criteria Stage A: Asymptomatic Stage B: B symptoms Stage C: AIDS Defining Conditions • Stage 1: CD4 >500 • Stage 2: CD4 200-500 • Stage 3: CD4 <200

  13. CDC HIV CLASSIFICATION SYSTEM CD4 Criteria Symptom Criteria Stage A: Asymptomatic Stage B: B symptoms Stage C: AIDS Defining Conditions • Stage 1: CD4 >500 • Stage 2: CD4 200-500 • Stage 3: CD4 <200 • For example, a 21 year old man with CD4 150 and no complications other than Thrush is stage B3

  14. Direct Viral Mediated End Organ Damage • HIV Associated Nephropathy • Focal Segmental Glomerulonephritis with Nephrotic Range Proteinuria • Rapid deterioration and progression to need for Kidney Replacement Therapy • HIV Associated Cardiomyopathy • Manifests like other viral cardiomyopathies • Can progress to need for ventricular assist device or cardiac transplant

  15. Direct Viral Mediated End Organ Damage • HIV Associated Dementia Complex • Cognitive abnormalities • Can also manifest motor abnormalities • Psychiatric disturbance is not uncommon • Significant progressive functional impairment • HIV Associated Minor Cognitive-Motor Disorder • Minor impairments in attention, concentration, memory, movement, coordination, memory, personality change • Often very slow to progress

  16. Direct Viral Mediated End Organ Damage • Hematologic Injury • Idiopathic Thrombocytopenic Purpura • Thrombotic Thrombocytopenic Pupura • Anemia, mild thrombocytopenia, relative leukopenia not emergencies • Nervous System • Peripheral Neuropathy • Vacuolar Myelopathy • Musculoskeletal • Myositis and Rhabdomyositis

  17. Direct Viral Mediated End Organ Damage • Suppression of HIV with Antiretroviral therapy can halt disease progression • Only option in most (except ITP and TTP) • Rapid initiation of antiretrovirals and suppression of viral load is imperative to prevent disease progression • This is also true for the Opportunistic Infection Progressive Multifocal Leukoencephalopathy

  18. Primary Prophylaxis in HIV VACCINES Opportunistic Infections Pneumocystis/Toxoplasma CD4 <200/100 Bactrim (DS/SS, QD/TIW) Dapsone 100 mg daily Atovaquone 1500 mg daily MAC (CD4 <50) Azithromycin 1200 mg Weekly/divided Twice Week • Pneumovax • Prevnar • Influenza • TDAP • Hepatitis A • Hepatitis B • Zostavax (CD4>200) • HPV Vaccine (age 13-26)

  19. Primary Prophylaxis in HIV • Special Cases • Residing in an area endemic for Histoplasmosis and CD4<150: Itraconazole 200 mg daily • Residing in an area endemic for Coccidioides and CD4<250: Fluconazole 400 mg daily • Residing in an area endemic for Penicilliosis and CD4<100: Itraconazole 200 mg daily

  20. Endemic Areas for Coccidioidomycosis

  21. Endemic Areas for Histoplasmosis

  22. Endemic Areas for Penicilliosis

  23. TAKE HOME MESSAGES • Mono-like illness: Consider Acute HIV • Vaccinate: Prevnar, Pneumovax, Influenza • Stage and Prophylax • CD4 count < 200: Pneumocystis • CD4 count <100: Toxoplasmosis • CD4 count < 50: MAC • End Organ Damage is an HIV Emergency • HIVAN • Dementia • Cardiomyopathy

  24. A 28 year old African American man presents to your clinic with complaints of 2 days of fever, night sweats, and sore throat. He admits to accepting money from men in exchange for unprotected sex starting three months ago. Exam reveals thrush, swollen cervical and inguinal lymph nodes, a flat erythematous rash on his trunk. Which test is most likely to be diagnostic right now? • HIV ELISA Antibody Test • Oraquick HIV Antibody Test • HIV Western Blot Test • HIV 4th Generation Antigen/Antibody Test • CD4 count

  25. A 28 year old African American man presents to your clinic with complaints of 2 days of fever, night sweats, and sore throat. He admits to accepting money from men in exchange for unprotected sex starting three months ago. Exam reveals thrush, swollen cervical and inguinal lymph nodes, a flat erythematous rash on his trunk. Which test is most likely to be diagnostic right now? • HIV ELISA Antibody Test • Oraquick HIV Antibody Test • HIV Western Blot Test • HIV 4th Generation Antigen/Antibody Test • CD4 count

  26. Window Period

  27. HIV Update and State of the Art HIV TESting

  28. CDC HIV Testing Recommendations:HIV screening is normal medical practice • HIV screening is recommended for patients in ALL health-care settings (opt-out screening) – particularly pregnant women • High Risk Persons should be screened annually • Separate written consent should not be required • Repeat screening should occur for pregnant women in the 3rd trimester

  29. Terms • High Risk (Expanded!!) • IDU and their sex partners • Commercial sex workers • Partners of HIV infected persons • Men who have sex with men (MSM) • Persons who have had more than 1 sex partner since their most recent HIV test (or their partners)

  30. Tests Available • Antibody Tests (confirmatory WB required) • Laboratory Blood Tests • Rapid Blood Tests (multiple) • Home Access/Express HIV-1 Test System using fingersticks • Home Rapid Tests (Oraquick, Orasure) using Saliva • Western Blot (Confirmatory) • Positive: 2 of the following – p24, gp41, gp120/160 • Indeterminate: any positive bands • Negative: no positive Bands • 4th Generation HIV Antibody/Antigen Tests

  31. 4th Generation • Architect HIV-1/2/O/M Ag/Ab Combo (Lab) • Alere Determine HIV-1/2 Ag/Ab Combo (Rapid) • Reflex testing • Reflex to HIV1 and HIV 2 specific testing • If either test is positive, then the patient has a positive test for either HIV1 or HIV2 and no Western Blot required • If both negative then reflex to viral load testing • If viral load test is positive, then patient has a positive test and no Western Blot is required

  32. TAKE HOME MESSAGES • All adults (and sexually active adolescents) should be tested on entry into medical care • Repeat annual testing in high risk groups (living in DC is a high risk group – see next section!) • Rapid Tests and Home Tests still need confirmation • 4th Gen Test will detect infection in the “Window Period” • Otherwise, use Nucleic Acid test to detect infection in the “Window Period”

  33. Which of the following locations is estimated to have a higher prevalence of HIV than the others listed? • Ethiopia • Haiti • Guinea-Bissau • Washington, DC • Sierra Leone

  34. Which of the following locations is estimated to have a higher prevalence of HIV than the others listed? • Ethiopia (1.4 %) • Haiti (1.8%) • Guinea-Bissau (1.4%) • Washington, DC (2.7%) • Sierra Leone (1.6%)

  35. Which of the following locations is estimated to have a higher prevalence of HIV than the others listed? Washington, DC (2.7%) Swaziland (26%) Mozambique (11.3%) Botswana (23.4%) Malawi (10%) Lesotho (23.3%) Uganda (7.2%) South Africa (17.3%) Kenya (6.2%) Zimabwe (14.9%) Tanzania (5.8%) Nambia (13.4%) Gabon (5%) Zambia (12.5%)

  36. HIV Update and State of the Art Epidemiology

  37. WHO Global summary of the AIDS epidemic 2011 Total Adults Women Children (<15 years) Total Adults Children (<15 years) Total Adults Children (<15 years) 34.0 million [31.4–35.9 million] 30.7 million [28.2–32.3 million] 16.7 million [15.4–17.6 million] 3.3 million [3.1–3.8 million] 2.5 million [2.2–2.8 million]2.2 million [1.9–2.4 million] 330 000 [280 000–390 000] 1.7 million [1.5–1.9 million]1.5 million [1.3–1.7 million] 230 000 [200 000–270 000] Number of people living with HIV People newly infected with HIV in 2011 AIDS deaths in 2011

  38. Adults and children estimated to be living with HIV  2011 Eastern Europe & Central Asia 1.4 million [1.1 million – 1.8 million] Western & Central Europe 900 000 [830 000 – 1.0 million] North America 1.4 million [1.1 million – 2.0 million] East Asia 830 000 [590 000 – 1.2 million] Middle East & North Africa 300 000 [250 000 – 360 000] Caribbean 230 000 [200 000 – 250 000] South & South-East Asia 4.0 million [3.1 million – 5.2 million] Sub-Saharan Africa 23.5 million [22.1 million – 24.8 million] Latin America 1.4 million [1.1 million – 1.7 million] Oceania 53 000 [47 000 – 60 000] Total: 34.0 million [31.4 million – 35.9 million]