HIV in the ED

1. HIV in the ED Vicken Y. Totten MD Director, UH HIV Initiative

2. Objectives • Define and discuss HIV: the virus & HIV: the infection • Discuss how HIV infection without AIDS manifests • Define and discuss AIDS, the disease • Discuss transmission and prevention • Describe the illnesses associated with HIV infection so you can recognize them and initiate treatment • Tell a brief history of ED-based HIV testing.

3. AIDS = Acquired Immune Deficiency Syndrome • Acquired - because it's a condition one must acquire or get infected with, not something transmitted through the genes • Immune - because it affects the body's immune system, the part of the body which usually works to fight off germs such as bacteria and viruses • Deficiency - because it makes the immune system deficient • Syndrome - because someone with AIDS may experience a wide range of different diseases and opportunistic infections

4. What is HIV, the Virus? • Any of several retroviruses that infect and destroy helper T cells of the immune system • Most likely, a simian retrovirus (Zoonosis)

5. The Human Immune Deficiency Virus

6. HIV-1 More virulent Responsible for worldwide epidemic Severity of infection varies from person to person HIV-1 likely descended from SIVcpz HIV-2 Primarily found in western Africa Not transmitted as efficiently Genome more closely related to SIVmm than HIV-1 HIV-2 likely descended from SIVsm Two Kinds of Virus: HIV-1 vs. HIV-2

7. HIV, the Virus • Retro-Virus: copies itself “backwards” from RNA into the host DNA. Makes lots of errors leading to a high mutation rate • Targets macrophages, especially CD4 cells • Most infectious during the first viremic episodes. Requires “intimate contact” for transmission • Destroys the body’s ability to fight infections and certain cancers • Therefore, untreated patients infected with HIV are at risk for illness and death from: • Opportunistic infections • Neoplastic complications

8. History: When did the zoonosis jump species? • Three earliest known HIV infections • 1959 - serum sample from a man in what is now the Democratic Republic of Congo • 1969 - tissue from a St. Louis teen • 1976 - tissue from a Norwegian Sailor • 2000 - Dr. Bette Korber estimates SIV-> HIV occurred about 1930, based on computer modeling. • 1979 - The “HIV Epidemic” in the USA brought by “patient 0”, a homosexual Canadian Airline Steward who was exceptionally sexually active wherever he flew.

9. Top HIV/AIDS-Infected Countries • South Africa • Nigeria • Zimbabwe • Tanzania • The Congo • Ethiopia • Kenya • Mozambique 9. United States 10. Russian Federation 11. China 12. Brazil 13. Thailand Sub-Saharan Africa Source: Steinbrook R. The AIDS epidemic in 2004. NEJM. 2004;351:115-117.

10. Population Prevalence • One Baltimore inner city hospital found that up to 11% of patients had HIV Antibodies • 24% had either HIV or hepatitis B or C. • Therefore, all contacts with patients’ blood or body secretions must be considered to be potentially infectious by ED personnel.

11. HIV Positives in our ED • 2006, Radonich et al • Tested 666 samples of discarded blood from adult ED patients • 2.5% sero-positivity. • Of these, 1 / 4 - 1 / 5 are not aware they are positive • STDs flock together. If you find an STD, you should test for HIV

12. Proportion of AIDS Cases, by Race/Ethnicity

13. The Life Cycle of HIV-1 Structural Protein andEnzyme Precursors Viral RNA ViralDNA ViralRNA 1. Bindingand infection 2. Reversetranscriptionand integrationof viral DNA 3. Transcriptionand translation 4. Modificationand assembly 5. Budding andfinal assembly

14. HIV- Course of the infection • Inoculation: via internal contact, either thru a mucus membrane or into a body tissue • Window period: Before viral replication; after viremia but before immunologic response can be detected by RNA probes only • Antibody Tests positive: Saliva, blood, urine (?) • Asymptomatic: months to years • Symptomatic: Immune system cannot respond appropriately • Death

15. The Variable Course of HIV-1 Infection Typical Progresser Rapid Progresser Primary HIVInfection Primary HIVInfection Clinical Latency AIDS AIDS CD4 Level CD4 Level Viral Replication Viral Replication A B months years months years Nonprogressor Primary HIVInfection Clinical Latency CD4 Level Viral Replication ? C months years Reprinted with permission from Haynes. In: DeVita et al, eds. AIDS: Etiology, Treatment and Prevention. 4th ed. Lippincott-Raven Publishers; 1997:89-99.

16. HIV Hides in many organ systems Colon, Duodenum and Rectum Chromaffin Cells Brain Macrophages and Glial Cells Lymphocytes in Blood,Semen and Vaginal Fluid Lymph Nodes Thymus Gland Bone Marrow Lung Alveolar Macrophages Skin Langerhans’ Cells

17. Manifestations of HIV Infection

18. Leading Causes of Death in People Aged 25-44 Years in the US (1983-1998) 40 Unintentional injuries 30 Cancer Deaths per 100,000 Population 20 Heart disease Suicide HIV infection 10 Homicide Liver disease Stroke Diabetes 0 1988 1984 1990 1986 1992 1994 1996 1998 Year Gallant J. Planning for Long-Term Success in HIV Management. Satellite Symposium to the First IAS Conference on HIV Pathogenesis and Treatment, July 8 – 11, 2001.

19. Metabolic Glucose disorders insulin resistance impaired glucose tolerance hyperglycemia frank diabetes Lipid elevations increased triglycerides increased cholesterol Hyperlactatemia lactic acidosis Morphologic Fat accumulation abdominal obesity buffalo hump lipomatosis breast enlargement gynecomastia Fat loss appendices face buttocks Metabolic and morphologic complications associated with HIV. Sounds a lot like aging, doesn’t it? • Bone disease • Osteopenia , osteoporosis , avascular necrosis

20. Morphologic Complications: Peripheral Fat Loss (Lipoatrophy)

21. Morphologic Complications: Central Fat Accumulation (Lipohypertrophy)

22. Natural History of Untreated HIV Infection

23. Transmission and Prevention • “Intimate Contact” is a euphemism for “direct non-keratinized live tissue to tissue contact” • Saliva and tears are wet and can have virus, but also have high levels of accompanying antibodies • Semen > vaginal fluid have high viral loads and not so many antibodies • The virus cannot penetrate keratinized skin or latex; it dies when dried.

24. Who spreads HIV? • Those who don’t know they are infected. • Most who are at risk don’t consider themselves at risk • “Traditional risk groups” get tested • Those who know they are infected and are not protecting their partners • Those with low viral loads are LESS infective - but still infective • Knowingly infecting someone else is a criminal offense

25. Relative Amounts of HIV in Body Fluids Modes of Transmission: perinatal, parenteral, sex Low/Not Detectable High Moderate breast milk urine saliva feces sweat tears semen blood/ serum body cavity fluids vaginal fluid

26. Transmission and Prevention • IVDA or Blood / Blood product transfusions – direct inoculation • Transplantation (including corneas) • Semen into vagina – incomplete conversion per year in discordant couples • Semen into rectum – higher rate of conversion • Testing the “tissue donor” in window period may permit transmission

27. When does perinatal transmission occur? • Antenatal ∼20% • Intrapartum ∼80% • Breastfeeding ∼14%* *above baseline Lancet 340(8819):585

28. HIV Transmission Factors • AIDS / High Viral Load • STD / Exposure; open mucosa • Genital lesions • Frequency of unprotected sex • Lack of Circumcision

29. Who should be tested? • All pregnant women • Anyone presenting with an STD • Anyone with an unusual rash, mysterious febrile illness or unusual / opportunistic infection or cancer • Anyone with an unexpectedly low WBC

30. Screening for HIV infection • 2006 CDC recommendations changed. • Why? Several year plateau in rate of new infections. The current new positives primarily are those who do not see themselves at risk • Who? All people who come to EDs should be screened yearly • All people in the US at least once.

31. Occupational Exposure Risk • RNs most often exposed • ½ of emergency physicians reported > 1 / 2-year period. • 0.3% chance for percutaneous exposure • 0.09% for mucocutaneous splash exposure. • HIV transmission by health care workers to patients appears to be extremely rare.

32. Post-exposure Prophylaxis (PEP) • (1) type of exposure • (2) HIV status of the source • Separate recommendations for percutaneous vs mucus membrane or non-intact skin exposures. • Intact skin  no indications for therapy • Deep percutaneous exposures; • visible blood on a device, • injuries sustained during placement of a catheter in a vein or artery; • lower-risk percutaneous exposures are superficial or involve solid needles.

33. HIV Status of Source? • High-risk: • symptomatic HIV infection, • AIDS, • acute seroconversion, • high viral load; • Low-risk sources • asymptomatic HIV infection • viral load of less than 1500 copies/mL • Test Source: Negative Rapid Test Results is adequate to withhold or discontinue therapy. • Consider acute HIV infection -> assay of HIV RNA levels.

34. Non-occupational Exposure • Rape with significant exposure <72 hours; source known to be HIV-infected • 28-day HAART

35. PEP Regimen • Two-drug therapy options include zidovudine plus lamivudine (available as Combivir), • lamivudine plus stavudine, • didanosine plus stavudine. • PEP should be initiated within hours. • PEP is 4 weeks, if tolerated. • Discontinue PEP if the source is HIV-seronegative.

36. National Clinicians PEP Hotline providing 24-hour assistance, • CDC/University of California–San Francisco (UCSF) (1-888-448-4911), • University of California at Los Angeles (UCLA)'s online decision-making support webpage • (http://www.needlestick.mednet.ucla.edu).

37. The diseases associated with HIV infections • Acute Retroviral Syndrome • Chronic Retroviral Infection -> Chronic Inflammation & Decreased Immunity • Opportunistic infections • Cancers • Other diseases of reduced immunity

38. Acute Retroviral Syndrome • Requires a high index of suspicion • May have fever, fatigue, rash, pharyngitis as most common symptoms • Duration usually <2 weeks, but … • Diff dx: infectious mononucleosis, secondary syphilis, acute hepatitis A or B, roseola or other viral exanthems, toxoplasmosis • KEEP TESTING

39. Non-specific Rashes

40. Fever 80 – 90% Fatigue 70 – 90% Rash 40 – 80% Headache 32 – 70% Lymphadenopathy 40 – 70% Pharyngitis 50 – 70% Thrombocytopenia Arthralgias 5 – 70% Myalgia 50 – 70% Night sweats - 50% GI symptoms 30 – 60% Aseptic meningitis -24% Oral/genital ulcers 5 – 20% Lymphopenia Acute Retroviral Syndrome

41. AIDS – the Disease, Defined • HIV + with a CD4 cell count that is or has been less than 200 cells/mm3 • HIV + with a CD4 percent below 14%. • HIV + and has or has had an AIDS defining illness such as PCP, toxoplasmosis, MAC, Kaposi’s Sarcoma, etc. regardless of CD4 cell count

42. HIV-associated viral conditions • HIV wasting • HIV associated dementia • Progressive multifocal leukoencephalopathy • CD4+ lymphocyte count of <200 cells/microL  

43. AIDS-DEFINING ILLNESSES (1) HIV infection PLUS: • Cancers: • Invasive cervical cancer, Kaposi's sarcoma (an Herpes virus infection), Burkett Lymphoma, Primary Brain Lymphoma • Infections from symbiots • Candida of esophagus, trachea, or lungs • Herpes simplex: chronic ulcers >1 month's • Cryptosporidiosis, chronic intestinal (>1 month's duration)  

44. AIDS defining illnesses (2) • LUNGS: • Recurrent bacterial pneumonia • Pneumocystis jiroveci pneumonia   • Cryptococcosis, extrapulmonary   • Histoplasmosis: disseminated or extrapulmonary   • Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex  

45. AIDS defining illnesses (3) • Coccidioidomycosis: disseminated or extrapulmonary   • Cytomegalovirus disease (other than liver, spleen, or nodes), older >1 month   • Cytomegalovirus retinitis (with loss of vision)   • Extra-pulmonary histoplasmosis • Salmonella septicemia, recurrent   • Toxoplasmosis of brain, onset at age >1 month*  • Atypical Infections: M. avium. M kansasii, M. TB • Extrapulmonary coccidioidomycosis • Recurrent Salmonellosis

46. Anti-Retroviral Drugs Prophylaxis against chronic opportunistic infections. Chronic suppression of illnesses Brief overview of treatment

47. Highly Active Anti-Retroviral Therapy HAART • Collective name given to the most effective HIV regimens • Medications must be taken daily • Take all each day or none, • Missing medications can cause problems • Why?

48. Classes of Drugs • Nucleoside analog reverse transcriptase inhibitors - NRTI • Nucleoside Reverse Transcriptase Inhibitors • Nucleotide Reverse Transcriptase Inhibitors • Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) • Non-nucleoside reverse transcriptase inhibitors - NNRTI • Protease inhibitors - PI • Entry inhibitors - EI • Fusion Inhibitors (one approved by FDA) • Integrase inhibitor - II • Each works by a different mechanism; best used in combinations:

49. Class: NRTI Abacavir ABC Didanosine DDI Emtricitabine FTC Lamivudine 3TC Stavudine D4T Tenofovir TDF Zidovudine ZDV NNRTI Delavirdine DLV Efavirenz EFV Nevirapine NVP Protease Inhibitors PI Amprenavir APV Atazanavir ATV Darunavir DRV Fosamprenavir FPV Indinavir IDV Lopinavir LPV Nelfinavir NFV Ritonavir RTV Saquinavir SQV hard gel HGC tablet INV Tipranavir TPV Anti-retroviral Medications

50. Newer Classes • CCR5 - Coreceptor Antagonist • Maraviroc MVC • II - Integrase Inhibitor • Raltegravir RAL • FI - Fusion Inhibitor • Enfuvirtide T-20