Diagnosing HIV UCLA AAHU Science and Treatment College Science Academy 2014

Outline of Talk  Principles of Diagnosing HIV  How HIV is Diagnosed  Consequence of Diagnosing HIV  Discussion questions

History of HIV Testing  HIV as the cause of AIDS discovered several years after the disease was first characterized  Tests to detect HIV infection developed in 1985  Initial large scale testing was focused on testing blood supply  Testing in individuals became more widespread due to multiple factors:  Knowledge that HIV spread with sexual contact and from mother to child  Development of successful treatments

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

Reasons Diagnosing HIV infection Important  Early diagnosis can allow for early treatment  More evidence shows this can improve disease outcome  Effective treatment also decreases likelihood of spread  Partners of HIV infected individual can also be tested

HIV is Under-Diagnosed  It is estimated that 16% of people living with HIV in the United States are unaware of their diagnosis  In one study in New York, 32,534 consecutive patients were screened for HIV; 0.45% tested positive, and of these, 29% were new diagnoses  In Sub-Saharan Africa as many as 50% of people living with HIV are undiagnosed

Question: Who Should Be Tested for HIV? Screening vs. targeted testing, and issues of confidentiality

Universal HIV Screening  Major guidelines are similar  2006 CDC: all patients age  2009 American College of Physicians: all patients age  2013 U.S. Preventative Services Task Force: all patients age  The bottom line: everybody in the US should be screened  This is most practically done at the first “establish care” visit or at the time of a first hospitalization  Exception: if the established prevalence of HIV is < 0.1% (e.g. in North Dakota)

Frequency of Screening  For persons who are “low-risk,” one time is reasonable  For high-risk patients, can be up to every three months  IV drug use  Men who have sex with men  Partners of HIV infected individuals or individuals with unknown HIV status  Sex workers  People taking pre-exposure prophylaxis

Targeted Testing  Recent HIV exposure  Symptoms suggestive of new HIV infection  Occupational exposure (e.g. needle stick)  Blood or organ donors  Pregnancy (every time)

Consent and Confidentiality  Do you need consent before you test somebody?  Historically, written consent was required prior to testing a patient for HIV  In 2006 CDC instead recommended “opt-out” testing, i.e. the patient is informed verbally that an HIV test will be sent, and she has the ability to decline, or “opt-out”  Since 2006 every state except Nebraska has eliminated written consent for HIV testing  With increased testing, confidentiality is essential  Patients should always be reassured and reminded that their results will only be discussed with them

Discussion Question 1: Which of the following patients do NOT need to be tested for HIV? A) Healthy 34yo woman presenting to establish care under her new HMO B) 72yo man who presents to the emergency room with chest pain C) 20yo man with Down syndrome, developmental delay, admitted for pneumonia D) 50yo man presenting with fevers, rash, and swollen lymph nodes after a business trip to Thailand

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.

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 are non-specific:  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

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

Classification of HIV Disease: WHO Stages

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

Classification of HIV Disease: WHO Stages (cont.)

HIV wasting syndrome (WHO stage IV) Oral Candidiasis / Thrush (WHO stage III)

Classification of HIV Disease: CDC Stages  Stage 0: Early infection (within 6 months of infection)  Stages 1, 2, and 3: Based on CD4+ T cell count and if an opportunistic infection has occurred

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 †  Pneumocystis jirovecii pneumonia †  Pneumonia, recurrent †§  Progressive multifocal leukoencephalopathy  Salmonella septicemia, recurrent  Toxoplasmosis of brain, onset at age >1 month †  Wasting syndrome attributed to HIV

Karposi Sarcoma: HHV-8 Non-Hodgkin Lymphomas:

Discussion Question 2: 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?

Discussion Question 2:  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).

Question: How is the diagnosis of HIV made? (Part II) A brief overview of HIV laboratory tests

Image modified from rom niaid.nih.gov Detect antibodies Detect virus components

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

Available HIV Tests  Detection of virus components (early infection)  p24 Antigen test  HIV viral RNA test  Detection of host antibody response (2-3 weeks after infection)  ELISA  Immunofluorescence assay  Western Blot  Rapid HIV test

Discussion Question 3: 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?

Discussion Question 3:  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 viral components (RNA and p24 capsid protein)

Question: What are the consequences of a new diagnosis of HIV? A brief word on the psycho-social elements of HIV diagnosis

Psychosocial Consequences  HIV diagnosis is life-altering, shocking, and psychologically disturbing  Depression is common  It profoundly affects all of the patient’s relationships  Important to provide psychological and mental health services  Important to communicate that HIV is a chronic disease and with proper treatment, life expectancy is normal

Summary  Diagnosing HIV is crucially important for individual health and public health  Universal screening is recommended, with additional targeted testing as indicated  Diagnosis is made by clinical history and two basic types of laboratory tests  The more people we diagnose with HIV the more we have to be prepared to help people learn to live with the disease

Thank You!

References  Bartlett, Hirsch, and Mitty, UpToDate, “Screening and diagnostic testing for HIV infction” 2014  CDC. Detection of Acute HIV Infection in Two Evaluations of a New HIV Diagnostic Testing Algorithm – United States, , MMWR 2013; 62(24):  Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at Published June 27,  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- United States, MMWR Recommendations and Reports Vol. 63 No. 3

References  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. AIDS 2013; 27:  Lin et al., Routine HIV screening in two health-care settings--New York City and New Orleans, MMWR Morb Mortal Wkly Rep. 2014;63(25):537.  Schweitzer, Mizwa, and Ross, Psychosocial aspects of HIV/AIDS: Adults  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, 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.