Acute HIV Infection - UCLA Center for World Health
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African American HIV University Wednesday, August 26, 2015 Acute HIV Infection Oladunni Adeyiga, MD, MS STAR Fellow Department of Medicine Division of Infectious Diseases 2 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Outline • Cases • Learning Objectives • Brief HIV Introduction • Acute HIV Infection: • Clinical Syndrome, Biology, Diagnosis • Other things to consider: • Reporting, Additional tests, Counseling • Cases and Practice Questions • Summary • Questions 3 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Cases 4 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 1 A 27-year-old previously healthy man presents to an urgent care center with fever, sore throat, lymphadenopathy, severe fatigue, and a diffuse rash. His symptoms have been present for approximately 48 hours and his history reveals unprotected receptive anal intercourse with another man 12 days prior to the onset of his symptoms. He had a negative HIV antibody test approximately 6 months ago. http://www.hivwebstudy.org/cases/initial-evaluation/acute-primary-hiv-infection Adapted case from HIV Web Study. Accessed on August 14, 2015 5 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 2 • A 25-year-old man reports that five weeks prior to going to the doctor, the patient had sexual contact with a new male partner who was infected with HIV and was not taking antiretroviral therapy (ART). Two weeks later, he experienced the rapid onset of fatigue, fevers, sweats, and sore throat, followed by a generalized rash, and headache. At that time, he was tested for HIV infection (via antibody testing), which was negative, but viral load testing was elevated. Kim, JY, et. al. (2014) J Int Assoc Prov AIDS Care; 133): pp 196 - 199 Adapted case 6 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 3 A 19 year old girl comes to clinic, after feeling ill for approximately 2 months. Her friends think that she has “mono,” because she’s always tired, and she’s had swollen nodes on and off. She doesn’t have a great appetite. She’s nervous, she usually has her mom with her at all her doctor’s appointments, but currently she’s away at school. During the evaluation, she shares with the doctor that she recently broke up with her 1st boyfriend last week. They met 4 months ago, she thought she was in love, but she caught him cheating with someone else. The doctor asks her about HIV testing, and she is adamant: “There’s no way that could be the problem.” 7 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Learning Objectives 8 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Learning Objectives • Understand the time course of symptom onset and resolution in acute HIV infection • Understand the biology of acute HIV infection • Understand the risk factors of HIV acquisition • Understand how to diagnose acute HIV infection • Understand the regulatory guidelines with regard to diagnosing and reporting acute HIV infection • Understand how to counsel newly diagnosed patients 9 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV - Brief History 10 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 FDA History Timeline* *Source: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm117935.htm Accessed August 11, 2014 • 1981: First case reports • 1982: AIDS terminology used by CDC • 1983: Identification of HIV as virus leading to AIDS 11 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Gottlieb, MS., et. al. (1981) MMWR; 30(21): pp 1-3 12 1Gottlieb, MS, et. al. (1981) NEJM; 305(24): pp 1425 -1431 2Masur, H., et. al. (1981) NEJM; 305(24): pp 1431-1438 3Siegal, FP, et. al. (1981) NEJM; 305(24): pp 1439 -1444 13 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: Clinical Syndrome 14 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Estimated New HIV Infections in 2010 CDC. Estimated HIV incidence among adults and adolescents in the US, 2007–2010. HIV Surveillance Supplemental Report (2012);17(4). 15 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Additional Terms Used in Literature • Acute HIV Infection: Refers to symptomatic early infection • Recent HIV Infection • Early HIV Infection: Refers to 6 month period after initial infection • Note: 10-60% of patients WILL NOT have symptoms! Sax, PE. Acute and early HIV infection: Clinical manifestations and diagnosis. www.uptodate.com; Updated July 2015. Accessed August 14, 2015. 16 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Modes of Transmission • Sexual contact • Exposure to infected blood • Perinatal transmission Bartlett, JG. The natural history and clinical features of HIV infection in adults and adolescents. www.uptodate.com; Updated July 2015. Accessed August 14, 2015. 17 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection; Risk Factors for Transmission or Acquisition of Virus • Increased viral load • Sexual behavior/practices • Sexually transmitted infections (STIs) • Lack of circumcision • Genetic background Bartlett, JG. The natural history and clinical features of HIV infection in adults and adolescents. www.uptodate.com; Updated July 2015. Accessed August 14, 2015. 18 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection; Clinical Presentation— Symptoms • Fever, sore throat, rash, muscle/joint aches, headache • Acute retroviral syndrome • Additional symptoms: • Gastrointestinal: • Neurological: • Swollen nausea, vomiting, diarrhea headache, neck stiffness. nodes, fatigue • Mucocutaneous ulcers (mouth sores) • Mononucleosis–like syndrome • Onset: Usually 2-4 weeks after exposure • Resolution: Most self-resolve; time course varies. Sax, PE. Acute and early HIV infection: Clinical manifestations and diagnosis. www.uptodate.com; Updated July 2015. Accessed August 14, 2015. 19 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Clinical course of HIV Infection without therapy: Summary Elite Controllers Acute Infection Long-term nonprogressors 0 Clinical latent period 6 months Early Symptomatic HIV Infection Time Advanced HIV Infection Years 20 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: the Biology 21 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV (Previously named HTLV III) Virions Budding from pre-AIDS patient’s Lymphocytes Gallo, RC., et. al. (1984) Science; 224(4648): pp 500-503 22 Rationale for and Goals of ARV Treatment Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV Life Cycle 3. Integration 1. Cell entry 2. Reverse Transcription 4. Protein assembly 5. Budding Tsibris, AMN and Hirsch, MS. (2010). Chapter 128. Antiretroviral Therapy for Human Immunodeficiency Virus Infection Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (7th Ed.). Philadelphia, PA: Churchill Livingstone/Elsevier 23 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV (Previously named LAV)Virions Budding from a Lymphoblastoid Cell Montagnier, L., et. al. (1984) Science; 225(4657): pp 63-66 24 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV-1 Virion Structure Reitz, Jr., RS and Gallo, RC. (2010). Chapter 169. Human Immunodeficiency Viruses. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (7th Ed.). Philadelphia, PA: Churchill Livingstone/Elsevier 25 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Early Infection • Transmission of virus: “founder virus” • Virus and/or virus-infected cells meet immune cells • Activated CD4+CCR5+ T cells • Dendritic cells (DCs) • The virus spreads rapidly to other lymphoid tissues • e.g. Gut-associated lymphoid tissue (GALT) • Significant decrease in CD4+ T cells in the gut • Impairment • HIV in B-cell responses Reservoir is established McMichael, AJ, et. al. (2010) Nature Reviews Immunology; 10(1): pp 11-23 26 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Definition of Acute HIV Infection McMichael, AJ, et. al. (2010) Nature Reviews Immunology; 10(1): pp 11-23 27 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: Diagnosis 28 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Stages of Early Infection: Diagnostic Assays Patient 51 Patient 45 Patient 7 ■ ● ○ (N/I/P*/P) LEGEND HIV RNA Viral Load HIV Ab signal/cutoff (s/co) p24 Ag (s/co) HIV Western blot band patterns N = Non-reactive, I = indeterminate P* = reactive without p31 band P = fully reactive Feibig, EW, et. al. (2003) AIDS; 17(21): pp 1871 - 1879 29 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Stages of Early Infection: Diagnostic Assays RNA = Ab = LS-Ab = p24 Ag = ecl. = LEGEND HIV RNA Viral Load HIV Ab HIV Ab tested by by sensitive/less sensitive enzyme immunoassay (EIA) testing p24 Antigen Eclipse phase HIV Western blot band patterns (N/I/P*/P) N I P* P = = = = Non-reactive Indeterminate Reactive without p31 band Rully reactive Fiebig Stages: 0, I, II, III, IV, V, V Feibig, EW, et. al. (2003) AIDS; 17(21): pp 1871 - 1879 30 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Laboratory Stages: Fiebig classification* Fiebig Stage Cumulative Duration** HIV RNA Days 95% CI I 5.0 (3.1,8.1) + II 10.3 (7.1,13.5) III 13.5 IV V VI p24 antigen Antibody (EIA) Western blot NS S - - - - + + - - - (10.0,17.0) + + - + - 19.1 (15.3, 22.9) + +/- - + Indeterminate 88.6 (47.4,129.8) + +/- +/- + + (p31 band neg) + +/- + + + (p31 band pos) Open-ended *Based on detection in blood **Calculations made based on a parametric Markov model (statistical modeling) Feibig, EW, et. al. (2003) AIDS; 17(21): pp 1871 - 1879 31 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Stages of Early Infection: Diagnostic Assays Eclipse phase: Usually ~10 days During this period viral RNA is not detectable in plasma McMichael, AJ, et. al. (2010) Nature Reviews Immunology; 10(1): pp 11-23 32 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: Diagnosis • Usually, detectable HIV RNA or p24 antigen with negative or indeterminate HIV antibody test result • Combination HIV Ag/Ab tests • Detect HIV-1 and HIV-2 and HIV-1 p24 Ag • Recommended by CDC as preferred assay for HIV screening, including for possible acute HIV-1 • Reactive specimens should be tested with assay that differentiates HIV-1 and HIV-2 • If reactive on Ag/Ab test but negative or indeterminate on Ab differentiation test: retest with quantitative or qualitative HIV-1 RNA test • If negative on RNA test: Ag/Ab was falsely positive • If positive: likely acute HIV-1; consider ART • Confirm HIV-1 infection with subsequent testing to document HIV Ab seroconversion www.aidsetc.org April 2015 32 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: Diagnosis • If initial testing done with assay that tests only HIV Ab: • If Ab is negative or indeterminate but acute HIV is suspected: • Check HIV RNA: if positive, presumptive diagnosis is acute HIV-1 HIV RNA (<10,000 copies/mL) may be false positive – repeat test on different specimen • Low-positive • If diagnosis is made by HIV RNA testing, confirm diagnosis with subsequent Ab testing www.aidsetc.org April 2015 34 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: The Practitioner’s Responsibility 35 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Practitioner’s Responsibility • Prior to diagnosis: • Opt-out testing • To the patient: • Evaluation: • Establish Baseline health, additional STIs location and relationship for continuity of care • Education regarding the new diagnosis • Public Health: Mandates for reporting 36 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 HIV Testing and Laboratory Reporting Laws http://www.cdc.gov/hiv/policies/law/states/index.html 37 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Acute HIV Infection: Patient Counseling 38 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Tuesday, September 2, 2014 Patient Counseling: Positive Result • Needs to occur before leaving the testing site. • Review the current state of treatment. • Multi-faceted to address the broad implications of this diagnosis • Medical (including reproductive implications) • Behavioral • Psychosocial • Be sure that the patient is linked up with care. • Stress the need for continued follow up http://www.cdc.gov/std/treatment/2010/hiv.htm 39 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Tuesday, September 2, 2014 Patient Counseling: Negative Result • Consider repeat testing • Prevention counseling • Discussion regarding patient behaviors • Modify/Reduce risky behaviors http://www.cdc.gov/std/treatment/2010/hiv.htm 40 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Practice Questions! 41 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Which of the following statements is FALSE about acute symptomatic HIV infection? A. It is also known as the acute retroviral syndrome. B. A patient cannot have acquired HIV infection unless the patient reports having symptoms. C. Common findings include fever, lymphadenopathy, sore throat, rash, muscle/joint aches, and headache. D. A patient who reports having a long duration of commonly reported symptoms and also has oral ulcers has clinical features that suggest acute symptomatic HIV infection. 42 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 The Fiebig stages are used to A. Classify patients who have advanced HIV infection and AIDS. B. Classify which patients will have acute HIV symptoms. C. Classify who is at risk for acute HIV infection. D. Classify when particular blood tests will identify a patient who has acute HIV infection. E. Classify a new dance move from the television show, America’s Got Talent. 43 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 The Eclipse phase: True or False A. During the eclipse phase in acute HIV infection, HIV RNA viral load is usually detectable. FALSE B. During the eclipse phase in acute HIV infection, HIV FALSE RNA levels and antibody testing will be positive. C. During the eclipse phase, transmitted virus replicates TRUE locally without systemic viral dissemination. D. The eclipse phase occurs before Fiebig stage 1 in acute HIV infection.TRUE E. In general, the patient will have symptoms during the FALSE eclipse phase. 44 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Tuesday, September 2, 2014 Cases 45 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 1 A 27-year-old previously healthy man presents to an urgent care center with fever, sore throat, lymphadenopathy, severe fatigue, and a diffuse rash. His symptoms have been present for approximately 48 hours and his history reveals unprotected receptive anal intercourse with another man 12 days prior to the onset of his symptoms. He had a negative HIV antibody test approximately 6 months ago. http://www.hivwebstudy.org/cases/initial-evaluation/acute-primary-hiv-infection Adapted case from HIV Web Study. Accessed on August 14, 2015 46 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 2 • A 25-year-old man reports that five weeks prior to going to the doctor, the patient had sexual contact with a new male partner who was infected with HIV and was not taking antiretroviral therapy (ART). Two weeks later, he experienced the rapid onset of fatigue, fevers, sweats, and sore throat, followed by a generalized rash, and headache. At that time, he was tested for HIV infection (via antibody testing), which was negative, but viral load testing was elevated. Kim, JY, et. al. (2014) J Int Assoc Prov AIDS Care; 133): pp 196 - 199 Adapted case 47 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Case 3 A 19 year old girl comes to clinic, after feeling ill for approximately 2 months. Her friends think that she has “mono,” because she’s always tired, and she’s had swollen nodes on and off. She doesn’t have a great appetite. She’s nervous, she usually has her mom with her at all her doctor’s appointments, but currently she’s away at school. During the evaluation, she shares with the doctor that she recently broke up with her 1st boyfriend last week. They met 4 months ago, she thought she was in love, but she caught him cheating with someone else. The doctor asks her about HIV testing, and she is adamant: “There’s no way that could be the problem.” 48 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Cases: Discussion with Role Playing 49 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Summary 50 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Summary • Risk factors for transmission include viral load, sexual practices, lack of circumcision, other STIs, and genetic factors. • Acute HIV Infection, also known as acute retroviral syndrome, can include symptoms such as fever, fatigue, rash, muscle/joint aches, sore throat, and mouth sores. • The HIV latent reservoir is established early in infection. • Fiebig stages, previously a research tool, helps in picking a diagnostic test to use for acute HIV infection. • Patient counseling is a key component in establishing linkage to and continuity of care for these patients. 51 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Questions? 52 Acute HIV Infection Oladunni Adeyiga, MD, MS African American HIV University Wednesday, August 26, 2015 Thank You! oadeyiga@mednet.ucla.edu 53
