1. HIV Recognition in the ED Martha I. Buitrago, MD Infectious Diseases Idaho State University

2. HIV in the ED Changing Epidemiology HIV Infection Presentations in the ED History Taking

3. 00003-E-3 – July 2004 Adults and children estimated to be living with HIV as of end 2003 Total: 37.8 (34.6 – 42.3) million Western Europe 580 000 [460 000 – 730 000] North Africa & Middle East 480 000 [200 000 – 1.4 million] Sub-Saharan Africa 25.0 million [23.1 – 27.9 million] Eastern Europe & Central Asia 1.3 million [860 000 – 1.9 million] South & South-East Asia 6.5 million [4.1 – 9.6 million] Oceania 32 000 [21 000 – 46 000] North America 1.0 million [520 000 – 1.6 million] Caribbean 430 000 [270 000 – 760 000] Latin America 1.6 million [1.2 – 2.1 million] East Asia 900 000 [450 000 – 1.5 million]

4. 00003-E-4 – July 2004 Children (<15 years) estimated to be living with HIV as of end 2003 Western Europe 6 200 [4 900 – 7 900] North Africa & Middle East 21 000 [6 300 – 72 000] Sub-Saharan Africa 1.9 million [1.7 – 2.2 million] Eastern Europe & Central Asia 8 100 [6 600 – 12 000] East Asia 7 700 [2 700 – 22 000] South & South-East Asia 160 000 [91 000 – 300 000] Oceania600 [< 2 000] North America 11 000 [5 600 – 17 000] Caribbean 22 000 [11 000 – 48 000] Latin America 25 000 [20 000 – 41 000] Total: 2.1 (1.9 – 2.5) million

5. 00003-E-5 – July 2004 Estimated number of adults and children newly infected with HIV during 2003 Total: 4.8 (4.2 – 6.3) million Western Europe 20 000 [13 000 – 37 000] North Africa & Middle East 75 000 [21 000 – 310 000] Sub-Saharan Africa 3.0 million [2.6 – 3.7 million] Eastern Europe & Central Asia 360 000 [160 000 – 900 000] East Asia 200 000 [62 000 – 590 000] South & South-East Asia 850 000 [430 000 – 2.0 million] Oceania 5 000 [2 100 – 13 000] North America 44 000 [16 000 – 120 000] Caribbean 52 000 [26 000 – 140 000] Latin America 200 000 [140 000 – 340 000]

6. 00003-E-6 – July 2004 Estimated number of children (<15 years) newly infected with HIV during 2003 Western Europe < 100 [< 200] North Africa & Middle East 8 400 [2 500 – 28 000] Sub-Saharan Africa 550 000 [500 000 – 650 000] Eastern Europe & Central Asia 1 500 [1 000 – 2 900] East Asia 3 300 [1 200 – 9 200] South & South-East Asia 47 000 [29 000 – 87 000] Oceania < 300 [< 1 000] North America < 100 [< 200] Caribbean 6 000 [3 000 – 13 000] Latin America 6 400 [5 100 – 10 000] Total: 630 000 (570 000 – 740 000)

7. 00003-E-7 – July 2004 Estimated adult and child deaths from AIDS during 2003 Total: 2.9 (2.6 – 3.3) million Western Europe 6 000 [<8 000] North Africa & Middle East 24 000 [9 900 – 62 000] Sub-Saharan Africa 2.2 million [2.0 – 2.5 million] Eastern Europe & Central Asia 49 000 [32 000 – 71 000] East Asia 44 000 [22 000 – 75 000] South & South-East Asia 460 000 [290 000 – 700 000] Oceania700 [<1 300] North America 16 000 [8 300 – 25 000] Caribbean 35 000 [23 000 – 59 000] Latin America 84 000 [65 000 – 110 000]

8. 00003-E-8 – July 2004 About 14 000 new HIV infections a day in 2003 l More than 95% are in low and middle income countries l Almost 2000 are in children under 15 years of age l About 12 000 are in persons aged 15 to 49 years, of whom: — almost 50% are women — about 50% are 15–24 year olds

9. 00003-E-9 – July 2004 Global estimates for adults and children end 2003 l People living with HIV l New HIV infections in 2003 l Deaths due to AIDS in 2003 37.8 million [34.6 – 42.3 million ] 4.8 million [4.2 – 6.3 million] 2.9 million [2.6 – 3.3 million]

10. 13.2 Million Children have been Orphaned Since the start of the Epidemic

23. Epidemiology  Changing demographics: 1998 2000 Women21% 27%  White38% 36%  Non-White41% 47%  MSM45% 42%  IVDU20% 25%  Heterosexuals19% 26% 

24. Idaho Cumulative HIV/AIDS 2003 -Cumulative statistics from April 1986 when HIV became a reportable disease in Idaho -HIV (+): Total # of HIV (+) individuals excluding Idaho AIDS cases

25. HIV in Idaho – Prevalence  District 195  District 2 46  District 3 101  District 4 333  District 5 76  District 6 64  District 7 46 Total 761 HIV / AIDS (As of June 2004)

26. Idaho Cumulative HIV/AIDS 2003 Exposure categories (Adults) Idaho HIV(+) (N=565) Idaho AIDS (N= 552) Men who have sex with men (MSM) 257 (45%)308 (56%) Injecting drug use (IDU) 95 (17%) 61 (11%) MSM & IDU44 (8%) Hemophilia/coagulation disorders 5 (1%)18 (3%) Heterosexual contact 73 (13%) 69 (13%) Receipt of blood component or tissue12 (2%) Other/risk not reported or identified 79 (14%)40 (7%)

27. Idaho Cumulative HIV/AIDS 2003 Exposure categories Pediatric Idaho HIV(+) (N=8) Idaho AIDS (N=3) Hemophilia/coagulation disorder0 (0%) Mother with/at risk for HIV infection 7 (88%)1(33%) Receipt of blood, components, or tissue 0 (0%)2 (67%) Other/risk not reported or identified 1 (13%)0 (0%)

28. HIV Presentations Primary HIV Infection Asymptomatic Screening Chronic HIV Infection Late-Stage AIDS  Mayo Clin Proc 2002;77:1097-1102

31. HIV Presentation

32. Case # 1 Mr. John Corporate is a pleasant 30 y.o male, captain of the baseball team. He comes to the ER with complaints of fatigue, sore throat, painful nodes on his neck, and generalized body rash. All symptoms started 2 months after his last business trip.

33. Case # 1 What other questions would you ask? What is your differential diagnosis? What tests would you order?

34. Acute HIV Infection: opportunities for diagnosis Physicians’ offices Emergency rooms Community health centers Dermatology clinics Sexually transmitted disease centers HIV clinics  Mayo Clin Proc 2002;77:1097-1102

35. Acute HIV Infection Transient symptomatic illness in 40-90% –nonspecific illness to severe manifestations –occasionally can result in hospitalization No specific constellation of signs or symptoms can differentiate acute HIV from other illnesses  Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339:33-39  Schacker, T, et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996;125:257-264

36. HIV Infection

37. Acute Retroviral Syndrome Fever Lymphadenopathy Pharyngitis Rash Myalgia/arthralgia Diarrhea Headache Nausea/Vomiting Hepatosplenomegaly Weight loss Thrush Neurologic symptoms  96%  74%  70%  54%  32%  27%  14%  13%  12%  CDC. Guidelines for using antiretroviral agents… MMWR 2002;51(RR-7)

38. Acute HIV Infection Symptoms present days to weeks after initial exposure Most common presentation: –fever, fatigue, headache, and rash Nonspecific symptoms overlap with common viral illnesses High index of suspicion is CRITICAL

39. Acute Retroviral Syndrome Rash (40-80%) –erythematous maculopapular with lesion on face and trunk (rarely extremities) –mucocutaneous ulceration involving the mouth, esophagus, or genitals Rash would help differentiate from infectious mononucleosis

40. Acute Retroviral Syndrome Neurologic symptoms (24%) –meningoencephalitis or aseptic meningitis –peripheral neuropathy or radiculopathy –facial palsy –Guillain-Barré syndrome –brachial neuritis –cognitive impairment –psychosis

41. Acute HIV DDX Influenza Epstein-Barr virus mononucleosis Severe (streptococcal) pharyngitis Secondary syphilis Primary CMV infection Toxoplasmosis Drug reaction Viral hepatitis Primary HSV infection Rubella Brucellosis Malaria West Nile Virus

42. Acute HIV: Diagnosis  Question all patients about HIV risk behaviors including sexual activity and injection drug use.  Perform a thorough physical examination with particular attention to the signs of primary HIV infection such as rash, mucocutaneous ulcers, and lymphadenopathy.  Perform a baseline HIV antibody test. –This serves two important purposes: it establishes whether chronic HIV infection is present the consent process initiates a discussion with the patient about the implications of HIV testing  Obtain an HIV viral load test, if the suspicion of acute HIV is high (the HIV antibody is likely to be negative in acute HIV infection)

43. HIV Antibody Tests Serum antibody (EIA) Saliva and urine antibody tests (EIA) Rapid tests –SUDS (microfiltration EIA) Laboratory-based –OraQuick Point of care Western blot assay –Confirmatory test

44. Potential Benefits of Treatment during PHI Suppress initial burst of viremia ? alter viral set-point Decrease viral evolution Preserve CD4 lymphocytes (both absolute number and HIV-specific) Potentially decrease risk of transmission Possibly allow for future cessation of therapy

45. Potential Risks of Treatment during PHI Drug toxicity Costs of possible lifelong therapy Starting therapy in patients who may never have needed it Early development of resistance Little evidence to date of clinical benefit

46. Acute HIV - Treatment Goal: long-term viral suppression Evidence: –Animal models (Macaques/SIV) –Small case reports Berlin patient, New York pair, Caracas couple

47. Weeks SIV RNA (log10), Median No Therapy STI-HAART HAART Lori et al. Science 2000 Acute Infection Control of SIV viremia w/ 3 wks on Rx & 3 wks off Rx Long term trial of 3 wks on & 3 wks off in SIV+ macaques

48. Lisziewicz et al. New Engl J Med. 1999. <500 10,000 20,000 30,000 40,000 50,000 60,000 70,000 80,000 90,000 HIV RNA, copies/mL 0 176....... Permanently discontinued Epididymitis 15–22 Hepatitis A 121–137 = No treatment Time, days -103070110150190230270310350390727 The Berlin Patient

49. Acute HIV: Missed Opportunity The symptoms — especially in mild cases — are nonspecific and resolve spontaneously without treatment. Clinicians may be uncomfortable raising the question of sexual exposure or intravenous drug-use, especially with patients whom they only see infrequently such as young, previously healthy individuals. Primary care physicians may not be aware of high-risk behavior even in patients they know well. Patients may not perceive themselves to be at risk.

51. Case # 2 MC is an 18 year old college student, who presents with increased shortness of breath for 3 weeks, fever, and non-productive cough. On exam, he has an oxygen saturation of 85% after exercise, and clear lungs.

52. Case #2 What other questions would you ask? What is your differential diagnosis? How would you treat?

53. Sexual History Taking Ensure privacy Be non-judgmental and respectful Avoid making assumptions about people Make eye contact, have relaxed body language Provide patients with a context for the questions that are to follow

54. Asking Questions First question is the most difficult; start with general, non-threatening Use open-ended questions Ask ‘how’, ‘what’, ‘where’ Avoid asking ‘why’ Ask about knowledge and use of barrier methods

55. Sample Questions Are you sexually active? How many sexual partners have you had in the past year? Do you have sex with men, women, or both? How are you protecting yourself from pregnancy?

56. Getting Started and the 5 “P”s Teens: –Some of my patients your age have started having sex. Have you? –What are you doing to protect yourself from AIDS or other STD’s? Adults: –I ask these questions to all my patients regardless of age or marital status….

57. The 5 “P”s 1.Partners 2.Sexual Practices 3.Past STDs 4.Pregnancy History 5.Protection from STDs

59. Importance of HIV Diagnosis Early Intervention services –Improved quality of life –Avoid complications –Healthcare maintenance Prevent transmission –Primary HIV infection Higher viral loads No antibody –Chronic infection Asymptomatic High risk behaviors

60. Chronic HIV Presentation Clinically latent Subtle clues Complicates other diseases Index of suspicion is CRITICAL

61. Mucosal Clues Oral Lesions –Thrush, hairy leukoplakia, gingivitis Genital –Recurrent candidiasis, cervical or anal dysplasia, STDs Gastrointestinal –Esophageal candidiasis, diarrhea, anorectal infections, cholangiopathy Mayo Clin Proc 2002;77:1097-1102

62. Hairy Leukoplakia

63. Oral Candidiasis ErythematousPseudomembranous

64. Dermatologic Clues Infectious dermatitides –Bacterial, fungal, viral Neoplastic –Kaposi’s, basal-cell, squamous cell Inflammatory –Psoriasis, seborrheic dermatitis Mayo Clin Proc 2002;77:1097-1102

65. Seborrheic Dermatitis Kaposi’s Sarcoma

66. Laboratory Clues Cytopenias –Anemia, ITP, leukopenia Hypergammaglobulinemia False positive results –RPR, ANA Elevated PTT Decreased cholesterol Renal insufficiency and protenuria Mayo Clin Proc 2002;77:1097-1102

67. Late-Stage Presentation Usually clinically obvious Should not be missed Opportunistic infections predominate Wasting common

68. Missed Opportunities Women who do not receive prenatal care Pregnant women who seek prenatal care erratically Non-legal residents Injection drug users Homeless Women who receive prenatal care but are not offered HIV testing E Aaron, CRNP. Presented at Clinical Pathway, August 2002.

69. Summary HIV/AIDS is an Idaho disease! Recognizing the presentation of HIV disease is important for ALL clinicians Identifying HIV-infected individuals is important for: –The person living with HIV –The spouse / partner –Unborn children –Society Referral specialty services ARE available