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Diagnosing HIV

Diagnosing HIV. UCLA AAHU Science and Treatment College Science Academy 2013. Outline of Talk. Why is diagnosing HIV important? How is the diagnosis of HIV made? What is measured with HIV laboratory testing? What are the case definitions of HIV infection? Discussion questions.

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Diagnosing HIV

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  1. Diagnosing HIV UCLA AAHU Science and Treatment College Science Academy 2013

  2. Outline of Talk • Why is diagnosing HIVimportant? • How is the diagnosis of HIVmade? • What is measured with HIV laboratory testing? • What are the case definitions of HIV infection? • Discussion questions

  3. Question:Why is diagnosing HIV important? To start early effective therapy and prevent spread of disease

  4. History of Testing • Cause of HIV discovered several years after AIDS identified andtests to detect HIV infection developed in 1985 • Initial large scale testing was focused on testing blood supply • Testing became more widespread due to multiple factors: • Knowledge that HIVspread with sexual contact and from mother to child • Development of successful treatments

  5. Reasons Reliable and Fast HIV Testing Important • Diagnosis cannot be quickly made based on symptoms alone • Early diagnosis can allow for early treatment • More evidence shows this can improve disease outcome • Effective treatment also decreases likelihood of spread • Fast diagnosis leading to treatment can improve mortality and decrease spread of disease

  6. Question:How is the diagnosis of HIV made? (Part I) Clinically: signs, symptoms, and clinical history should prompt suspicion of infection. Infection confirmed with laboratory testing.

  7. Clinical History and Presentation of HIV Infection: Early Disease • History of exposure: includes sexual exposure, injection drug use, healthcare setting exposure, mother to child transmission • Symptoms of acute infection: • Constitutional (non-specific): fever, fatigue • Also lymphadenopathy, sore throat, rash, muscle and joint pain, nausea/diarrhea, hepatitis, meningitis • 10-60% may not experience any symptoms

  8. Clinical History and Presentation of HIV Infection: Advanced Disease • Period of clinical latency follows acute infection • Period with relatively few symptoms or signs • Immune system continues to be affected leading to progressive immunosuppression and fall in CD4 T cells of the immune system • Severe immunosuppression eventually occurs • Leads to development of opportunistic infections and malignancies • Characterized by rare conditions not seen in people with intact immune systems

  9. Classification of HIV Disease: WHO Stages

  10. Herpes Zoster (Shingles): varicella zoster virus Seborrheic Dermatitis: Malassezia fungus

  11. Classification of HIV Disease: WHO Stages (cont.)

  12. Chronic Herpes Simplex Virus infections Esophageal Candidiasis: Candida fungus species

  13. Classification of HIV Disease: CDC Stages

  14. Classification of HIV Disease: CDC Stages: AIDS Defining Conditions • Bacterial infections, multiple or recurrent* • Candidiasis of bronchi, trachea, or lungs • Candidiasis of esophagus† • Cervical cancer, invasive§ • Coccidioidomycosis, disseminated or extrapulmonary • Cryptococcosis, extrapulmonary • Cryptosporidiosis, chronic intestinal (>1 month's duration) • Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month • Cytomegalovirus retinitis (with loss of vision)† • Encephalopathy, HIV related • Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month) • Histoplasmosis, disseminated or extrapulmonary • Isosporiasis, chronic intestinal (>1 month's duration) • Kaposi sarcoma† • Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex*† • Lymphoma, Burkitt (or equivalent term) • Lymphoma, immunoblastic (or equivalent term) • Lymphoma, primary, of brain • Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary† • Mycobacterium tuberculosis of any site, pulmonary,†§ disseminated,† or extrapulmonary† • Mycobacterium, other species or unidentified species, disseminated† or extrapulmonary† • Pneumocystisjirovecii pneumonia† • Pneumonia, recurrent†§ • Progressive multifocal leukoencephalopathy • Salmonella septicemia, recurrent • Toxoplasmosis of brain, onset at age >1 month† • Wasting syndrome attributed to HIV

  15. Karposi Sarcoma: HHV-8 Non-Hodgkin Lymphomas:

  16. Question:How is the diagnosis of HIVmade? (Part II) Screening of populations with laboratory testing

  17. Recommendations for HIV Screening: Who Should Be Screened? • All patients in any health-care setting • Persons with risk factors for HIV infection • Risk factors include IV drug use, men who have sex with men, partners of HIV infected individuals, partners of individuals with unknown HIV status, sex workers • Frequency of testing depends on risk factors and can be up to every three months • Prenatal testing for all pregnant women

  18. What is measured with HIV laboratory testing? Evidence of virus components and immune response

  19. Image modified from rom niaid.nih.gov

  20. From McMichael et al, Nat Rev Immunol, 2010; 10: 11-23

  21. HIV Laboratory Testing: Standard Screening Tests • Enzyme-linked Immunosorbent Assay (ELISA) • Indirect Immunofluorescence Assay (IFA) • Western Blot

  22. Differences in Standard Tests

  23. Standard Test Implementation and the Concept of Confirmation Testing • Initial testing done with antibody test such as ELISA which is good at screening for positive results (sensitivity) • This will ensure that as many people with HIV will have a positive test result • This may, however, also give some positive results in the absence of HIV infection (false positives) • If result is positive, a confirmation test done with Western Blot or IFA to confirm results • This test is highly reliable for detecting HIV (specific) • It may not have high sensitivity and also may be more costly and labor intensive, and therefore may not be ideal for initial screening

  24. Rapid HIV Tests • Based on detecting antibody to HIV infection • Test can be done on blood as well as saliva • Minimal equipment needed • Sensitivity comparable to ELISA • Also requires confirmatory tests when positive with Western Blot

  25. Tests that Detect Virus Components • p24 Antigen test • Becomes detectable before antibodies • Viral RNA test • Earliest detectable evidence of infection

  26. Differences in Tests Detecting Virus Components

  27. Question:What are the case definitions used to make a diagnosis of HIV infection WHO and CDC criteria

  28. Case Definitions: • Clinical Criteria: • History of exposure with associated risk factors • Signs and symptoms of disease • These may not be present in early or latent infection • Presence of typical conditions associated with HIV should prompt suspicion • Laboratory Criteria (from CDC and WHO): • one positive HIV antibody test with follow-up confirmation antibody test that detects different antibodies, and/or • positive test for viral components confirmed by a follow-up viral component test from another sample

  29. Discussion Question 1:A 24 year old man comes to clinic saying that he started a new sexual relationship with an HIV positive partner, and in the last 3 weeks he has been having some fevers and swollen lymph nodes with rash and diarrhea. One week ago he had a rapid HIV test done that was negative. Are you suspicious of HIV infection and how will you confirm your suspicions?

  30. Discussion Question 1: • Because of the history of exposure as well as the presence of symptoms typical of acute or early infection, suspicion is high • Having a negative rapid test is very likely because these tests usually test for antibodies. Antibodies may not be detectable in early infection • You will do further laboratory confirmation tests checking for RNA

  31. From McMichael et al, Nat Rev Immunol, 2010; 10: 11-23

  32. Discussion Question 2:A 34 year old woman comes to your clinic and is worried that she may have been infected with HIV. She had unprotected sex 6 years ago and for the past 3 years she has recurrences of what she has been told is genital HSV infection. This happens about once a year and lasts 2-5 days each time. Her recurrences have concerned her that she may have immunosuppression from HIV infection. Do you suspect HIV infection? How will you proceed?

  33. Discussion Question 2: • HIV infection is possible given an exposure history • HSV recurrence is associated with HIV infection, but with severe immunosuppression the recurrences last longer and are more severe • You will need to ask her more about her health, including if she has any symptoms of HIV infection. Because her exposure was 6 years ago, you will ask about conditions that occur at all stages of HIV infection (WHO stages) as well as conditions that are AIDS defining illnesses (CDC criteria) • Finally, if she does not have any other suspicious clinical findings or history, you will still screen her for HIV infection given her age and exposure history

  34. Discussion Question 3:A 70 year old man who is a resident of a nursing home has been having persistent weight loss and diarrhea. He has been evaluated by several physicians for possible GI diseases, but all that is revealed is some oral thrush (candidiasis) and persistent small amounts of blood in his stool. More recently, the patient has been having increasing confusion and disorientation. Do you suspect HIV infection? If so, could all his symptoms be explained by HIV infection?

  35. Discussion Question 3: • HIV infection should be suspected when someone presents with typical symptoms, regardless of age or their living situation • Because he is having symptoms of HIV infection, you would suspect advanced HIV infection • His weight loss and oral thrush are commonly associated with HIV infection. GI bleeding can be a result of Karposi Sarcoma or infection with opportunistic pathogen (CMV). His disorientation can also be due to HIV infection (encephalopathy) or infection with opportunistic infection (Cryptococcus).

  36. References • CDC. Detection of Acute HIV Infection in Two Evaluations of a New HIV Diagnostic Testing Algorithm – United States, 2011-2013, MMWR 2013; 62(24):489-494. • CDC. Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. 2006; 55(RR14):1-17. • CDC. Revised Surveillance Case Definitions for HIV Infection Among Adults, Adolescents, and Children Aged <18 Months and for HIV Infection and AIDS Among Children 18 Months to <13 Years --- United States, 2008. 57(RR10);1-8. • Mandell, G. (2010). Principles and Practice of Infection Diseases. Mandel, G., Bennett, John., Dolin, R. (Ed.). Philadelphia, PA. Churchill Livingstone Elsevier. • Nasrullah et al., Performance of a fourth-generation HIV_ screening assay and an alternative HIV diagnostic testing algorithm. AIDS2013; 27:731-737. • World Health Organization Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-Related Disease in Adults and Children. World Health Organization, 2007. Geneva. • World Health Organization. Guidelines for the Implementation of Reliable and Efficient Diagnostic HIV Testing, Region of the Americas. Pan American Health Organization, 2008, Washington D.C.

  37. Thank You!

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