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HIV Diagnosis, Acute Infection and Superinfection

HIV Diagnosis, Acute Infection and Superinfection. Don Kurtyka, ARNP, MS, MBA University of South Florida College of Medicine Tampa General Hospital Hillsborough County Health Department. Objectives. Discuss the diagnosis of HIV and available tests

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HIV Diagnosis, Acute Infection and Superinfection

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  1. HIV Diagnosis, Acute Infection and Superinfection Don Kurtyka, ARNP, MS, MBA University of South Florida College of MedicineTampa General HospitalHillsborough County Health Department

  2. Objectives • Discuss the diagnosis of HIV and available tests • Describe the approach to the diagnosis of acute retroviral syndrome • Debate the advantages and disadvantages of early treatment of acute HIV infection • Discuss the evidence for the possibility of superinfection / reinfection and the implications for patient education and management

  3. Anonymous vs Confidential • Anonymous • Identifying information not provided • Results not linked to identifying information • Allows reporting of HIV infection without breaching confidentiality • Disadvantage: may not be able to locate clients for test results • Confidential • Clients linked to test result by identifying information • Results remain confidential • Informed consent

  4. Pre-Test Counseling • Goal: reduce HIV acquisition and transmission • Accurate and current information about HIV • Obtain informed consent • Transmission and acquisition • HIV test info: risk, benefits, meaning of potential test results • Assessment of individuals risks and appropriate risk reduction activities • Capacity to comprehend HIV testing and consent

  5. Post-Test Counseling • Accurate and current information about HIV • Local resources • Risk reduction education • Referrals for ongoing care and support • Healthy living strategies • Meaning of test results and state reporting guidelines • Mental health support / counseling

  6. Diagnosis of HIV Infection • Viral antibodies • Viral antigens • Viral RNA/DNA • Culture Lancet, 1996; 348: 176.

  7. Enzyme ImmunoassayEnzyme-Linked Immunosorbent Assay(EIA, ELISA) • Primary HIV antibody screening test • Serum plasma, dried blood spots, oral fluids, urine • HIV-1/2, HIV-1, HIV-2 • High degree sensitivity and specificity • Repeatedly reactive: confirmatory testing

  8. Negative Antibody Test Results • HIV negative • Recent infection: too early for seroconversion • CDC: follow-up testing at 6 weeks, 12 weeks, 6 months

  9. Confirmation Process • Non-negative screenings should be confirmed • Western Blot (WB) • Immunofluorescent Antibody Assay (IFA) • Higher specificity than EIA • Interpretation can be subjective

  10. Predictive Value: HIV Ab Tests • Depends on the prevalence of HIV infection in the population • Low HIV prevalence: predictive value of a positive test is low • HIV Ab testing of low prevalence populations likely to produce more false-positive than true-positive results

  11. Window Period • Time delay from infection to positive EIA • Average: 10-22 days • Most seroconvert within six months Am J Med 2000; 109

  12. HIV-1 vs HIV-2 • HIV-1: Most cases • Group M: predominant strain world-wide • Subtypes (clades): A to K, N, O • Clade B • US and Europe • 98% of HIV-1 in US • Most non-B subtypes were acquired outside US • Clade C: Southeast Asia • N (“new”): 1998 • Group O: West Africa • Recombination between viruses of different clades becoming more common

  13. Predominant HIV-1 Subtypes • A: West/East/Central Africa, East Europe, Mideast • B: North America, Europe, Mideast, East Asia, Latin America • C: South Africa, South Asia, Ethiopia • D: East Africa • E: Southeast Asia JAIDS 2002; 29:184

  14. HIV-2 • Primarily found in West Africa • Causes immune deficiency due to depletion of CD4 cells • 5-8 fold less efficient transmission compared to HIV-1 • Associated with lower viral load • Slower rate of CD4 decline and clinical progression • Negative Ab tests in 20-30% depending on EIA assay • WB: not well standardized nor FDA approved Bartlett, JG 2003: Medical Management of HIV Infection, p5.

  15. Testing Recommendations: HIV-2 • Natives of endemic areas • Needle-sharing and sex partners of persons from endemic areas • Sex or needle-sharing partners of persons with known HIV-2 infection • Transfusion or non-sterile injection recipients in endemic areas • Children of HIV-2 infected women

  16. Benin Burkina Faso Cape Verde Cote d’Ivoire Gambia Ghana Guinea Guinea-Bissau Liberia Mali Mauritania Niger Nigeria Sao Tome Senegal Sierrra Leone Togo HIV-2 Endemic Areas West Africa Other • Mozambique • Angola

  17. Confirmation Process: WB • Detects antibodies to HIV-1 proteins • Core: p17, p24, p55 • Polymerase: p31, p51, p66 • Envelope: gp41, gp120, gp160 • Negative: no bands • Positive: • Reactivity to gp41 + gp120/160 or • Reactivity to p24+gp120/160 • Indeterminate: • EIA repeatedly reactive • Presence of any band pattern not meeting criteria for positive results

  18. False Negative Results • High-prevalence population: 0.3% • Low-prevalence: <0.001% • Usually due to testing during window period • Rare patients seroconvert in late-stage disease • Technical or clerical error • Type N or O • HIV-2

  19. False Positive Test Results • Much less common than in earlier times • Frequency: 0.0004% to 0.0007% • Causes • Autoantibodies (single case, Lupus, ESRD) • HIV vaccines • EIA+: 68% • WB+: 0-44% • Technical / clerical error NEJM 1988;319:961 Ann Intern Med 1989;110:617

  20. Indeterminate Results • 4-20% of WB assays with positive bands • Testing during seroconversion • p24 usually appears first • Late stage HIV: loss of core antibody • HIV vaccine recipients • Technical / clerical error • Infection with O strain or HIV-2

  21. Indeterminate Results (continued) • Cross-reacting nonspecific antibodies • Collagen-vascular disease • Autoimmune disease • Pregnancy • Organ transplantation • Lymphoma, other malignancies • Liver disease • Multiple sclerosis • Recent immunization

  22. Indeterminate Results • Evaluate HIV risk • Low risk: almost never infected with HIV-1 or HIV-2 • Repeat testing: often continued indeterminate • Cause: frequently not established • HIV unlikely • Follow-up serology in 3 months • Seroconversion: usually WB+ in 1 month • Repeat testing at 1, 2, 6 months • Counseling to reduce potential transmission

  23. Frequency of HIV Testing • High risk behavior: every 6-12 months • Annual seroconversion • General population: 0.02% • Military recruits: 0.04% • MSM: 0.5 - 2% • IDU in high prevalence area: 0.7-6%

  24. Alternative Testing • Home test kits • Rapid Testing • Alternative body fluids • Saliva • Urine • Vaginal secretions • Viral detection

  25. Home Testing • Home specimen collection • Self-dried blood spot obtained with lancet • Anonymous coding • Mail/courier to testing facility • Double EIA and confirmatory IFA/WB • Sensitivity/Specificity: ~100% • Results relayed to user by telephone after user initiates request • Negative: prerecorded message • Positive: live conversation and counseling

  26. Rapid HIV Antibody Detection • Results in 15-20 minutes • Occupational exposure • Women in labor with unknown HIV status • Clients unlikely to return for visits • Outreach • ERs

  27. Rapid HIV Antibody Detection • OraQuick HIV-1 Antibody Test (OraSure) • Results read by provider in 20 minutes • Sensitivity: 99.6% / Specificity: 100% • $20-30 • Testing initially delayed due to CLIA requirements • Fingerstick sample of blood • Negative test: definitive • Positive test: needs standard serology confirmation • Not recommended for HIV-2 screening

  28. Rapid HIV Antibody Detection • Single Use Diagnostic System (SUDS) HIV-1 Test • Venipuncture • Results: 15-30 minutes • Confirmatory WB required • Double Check (Organies)

  29. Type N, Type O, HIV-2 • EIA may fail to detect O subtype • N group: causes false-negative EIA but may be WB positive • HIV-2: false negative EIA in 20-30% • Consider specific HIV-2 testing

  30. P24 Antigen • Part of blood bank algorithms since 1996 • Uncommon in clinical practice • Detects free, non-complex HIV antigens in peripheral blood

  31. Typical Course of Primary HIV 1 mil HIV RNA 100,000 + HIV RNA HIV-1 Antibodies _ 10,000 Ab P24 + 1,000 Exposure 100 Symptoms 10 0 20 30 40 50 Days

  32. Rapid Test Results • Reactive (preliminary positive) rapid test • Screening test is positive • Preliminary result • Confirmatory testing required • Precautions to avoid viral transmission • Negative rapid test • No recent exposure: definitive negative • Possible recent exposure: • Recommend re-test • Counseling to prevent transmission

  33. OraQuick: Florida DOH • 6 Month Pilot Studies • Hillsborough CHD • Duval County Jail • Orlando CBO for substance abuse • Miami: 2 sites • Key West: only anonymous site

  34. Saliva Testing: OraSure • EIA and WB to detect IgG • Specimen collection device, antibody screen, WB confirmation • Cost: ~$25 • Specially treated pad placed between lower cheek and gum for 2 minutes • Vial sent to lab for processing • Sensitivity and specificity comparable to standard serologic testing (~99.5%) • Advantages: ease of collection; low cost; improved patient acceptance • Disadvantage: client must return for results

  35. Urine Testing • Calypte HIV-1 Urine EIA • Positive results require standard serologic confirmation • Sensitivity: 99%; Specificity: 94% • Cost: ~$4

  36. Vaginal Secretions • IgG EIA • CDC: recommended for rape victims • Semen contains HIV IgG Ab

  37. Indications for HIV Viral Detection • Confusing / indeterminate serologic test results • Acute retroviral infection • Neonatal infection • Window period following exposure • Not FDA approved for diagnosis of HIV • Expensive

  38. Viral Detection • p24 Antigen • HIV-1 DNA PCR • Most sensitive: able to detect 1-10 copies of proviral DNA • S/S: 99% / 98% • HIV-1 RNA (RT-PCR, bDNA) • S/S: 95-98% • Viral culture of PBMC: expensive, labor intensive, reliability variable

  39. Viral Detection: HIV-2 • bDNA proficient at quantitation of many non-clade B viruses • Amplicor version 1.5 designed to detect other clades

  40. National RecommendationsFor HIV Testing ofPregnant Women • USPHS Recommendations for HIV Screening of Pregnant Women (4-22-03) • Universal testing for all pregnant women as a routine part of prenatal care using an “opt out” approach • Labor and Delivery: routine rapid testing if HIV status unknown • Postnatal: rapid testing for all infants whose mother’s status is unknown • Regulations, laws, and policies about HIV screening of pregnant women vary from state to state

  41. Acute HIV Infection

  42. Acute HIV Infection • Transient symptomatic illness in 40-90% • Usually mild but can be severe • 2-6 weeks after infection • Often not recognized by primary care clinicians • Symptoms non-specific • Often resembles influenza, mononucleosis • “Cold symptoms” absent • Can be asymptomatic • Duration: 14 days DHHS Guidelines July 14, 2003

  43. Acute HIV Infection Neuro: meningoencepalitis or aseptic meningitis; peripheral neuropathy or radiculopathy; facial palsy, Guillain-Barre syndrome; brachial neuritis; cognitive impairment or psychosis CDC 2002

  44. Rash in Acute HIV Infection • Trunk, face, extremities • Palms and soles rarely involved • 5-10 mm diameter • Erythematous, nonpruritic, painless

  45. Laboratory FindingsAcute HIV Infection • Lymphopenia  lymphocytosis • Atypical lymphocytes • Transient CD4 decline • VL: 100,000 – 1,000,000

  46. Diagnosis of Acute HIV Infection • Recognition of clinical symptoms • No true constellation of signs/sympoms • Presence of any symptom(s) • History of activity associated with HIV risk • Detectable plasma HIV RNA • Highly sensitive • False positive possible • Detectable p24 Antigen • Less sensitive • False positive rare

  47. Acute HIV Infection • High virus levels (105-106 copies/mL) • 2-9% of HIV-negative have false positive results • Usually associated with low RNA titers <10,000 • VL in new infections • Correlates with rate of CD4 decline • Prognostic indicator in early disease

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