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HIV and TB

HIV and TB . Jeffrey D. Klausner, MD, MPH Professor of Medicine and Public Health Program in Global Health, Division of Infectious Diseases David Geffen School of Medicine Fielding School of Public Health Special thanks to: Caitlin Reed MD, MPH

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HIV and TB

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  1. HIV and TB Jeffrey D. Klausner, MD, MPH Professor of Medicine and Public Health Program in Global Health, Division of Infectious Diseases David Geffen School of Medicine Fielding School of Public Health Special thanks to: Caitlin Reed MD, MPH Medical Director, Inpatient TB Unit, Olive View – UCLA Medical Center Los Angeles County Department of Health Services August 20, 2013 African-American HIV University

  2. Disclosures • Dr. Klausner is a faculty member of the University of California Los Angeles • Dr. Klausner is a guest researcher with the US CDC Mycotics Diseases Branch • Dr. Klausner is a member of the WHO Congenital Syphilis Elimination advisory group • Dr. Klausner is medical director, APLA Health and Wellness Center • Dr. Klausner is a board member of Isis-Inc. • In the past 36 months, Dr. Klausner has received: • Travel support for meeting attendance from WHO, London School of Hygiene and Tropical Medicine and Council of Scientific Industrial Research, South Africa • Research grant funding, supplies or unrestricted gifts from the NIH, CDC, California HIV Research Program, Hologic Gen-Probe, Inc., Gilead Sciences, Inc., Cepheid, Inc., APLA, Public Health Foundation Enterprises, American Jewish World Service and Qpid.me JDKlausner@mednet.ucla.edu

  3. Objectives: TB Update • Review of TB epidemiology & pathogenesis • New tests and treatment for latent TB • Diagnosis of active TB • TB puzzles

  4. TB Frequency

  5. Reported TB Cases, U.S. 1982-2009 CDC MMWR 2010

  6. Where is TB? Global Tuberculosis Control 2011; WHO

  7. TB is Not Gone • 1/3 of the world’s population is infected with TB (Latent TB infection) • Globally 9 million new cases of active TB / year • 1.6 million TB deaths / year

  8. Tuberculosis Cases in Foreign-born and U.S.-born Persons by Race/Ethnicity: California, 2010 Credit: CDPH TB Control Program

  9. Natural History of TB Latent Infection • Asymptomatic • Not Infectious Exposure 90% X Infection • Active TB disease • 10% lifetime risk • 5% first 2 years after • infection 10% Close Aerosol Contact With an Infectious Case Treat latent TB to prevent active TB

  10. Relative Risk for Developing Active TB by Risk Factors Targeted Tuberculin Testing and Treatment of Latent TB InfectionCDC, MMWR June 2000

  11. Why do HIV-infected patients get TB? * 1) Immune suppression leads to activation of old TB 2) Re-exposure in clinics and hospitals leads to new infection

  12. Latent TB Infection

  13. Targeted TB screening 1) People at increased risk of recent infection • Close contacts of active TB case • Recent immigrants from countries with TB • Work exposure • Nursing home, hospital, jail/prison 2) Risk factors for active TB • Pts with HIV infection • Other immunosuppressed persons

  14. TB Screening Tests • Tuberculin skin test (TST) • Interferon-gamma release assays (IGRAs) • Quantiferon-Gold In-Tube (Cellestis) • T. Spot TB (Oxford Immunotect) • Quantiferon is the most commonly use TB screening test in patients with HIV-infection *

  15. TB Skin Test 48-72 hrs • Interpretation depends on risk factors • Reader error • No immune response in some pts • Reactivity

  16. Quantiferon TB Testing • Measures immune response to TB antigens • Similar principle to TST • Uses TB-specific antigens • Not affected by BCG vaccination (specific)

  17. TST and Quantiferon IFN- Presentation of mycobacterial antigens TNF- IL-8, etc. Tuberculin skin test IFN- Antigen presenting cell Memory T-cell TNF- IL-8, etc. IGRA Andersen P, et al. Lancet 2000;356:1099

  18. Case 1 • 32 year old health care worker with positive QuantiferonTest • Denies cough, fever, weight loss, night sweats • Chest x-ray negative • Treat for latent TB infection • 9 months isoniazid daily or • 4 months rifampin daily or • 3 months of isoniazid/ rifapentineweekly

  19. Treatment of latent TB in patients with HIV infection • 6 months of isoniazid • Some recommend 36 months • ? Perhaps until CD4 > 500

  20. Active TB Latent TB Infection Active TB Infection Symptomatic Exposure Death Treatment

  21. TB Diagnostic Tests • Smear microscopy (sputum, tissue) • Mycobacterial Culture (sputum, blood, tissue) • Nucleic Acid Amplification Tests (sputum, tissue)

  22. Sputum Smear Microscopy • Easy, rapid, cheap • Sensitivity*: • In field conditions : 40-60% • HIV- infected patients: 20-60% • Specificity: Not specific for M. tuberculosis Arrow: Acid Fast Bacilli *WHO Stop TB Diagnostics Working Group Strategic Plan 2006-2015

  23. Mycobacterial Culture • Reference Standard for diagnosis of TB • Can send from any body site • Solid or liquid culture medium • Limitation: • Slow (mean: 24 days for positives) • Resource intensive, costly

  24. Drug Susceptibility Culture Testing • Diagnosis of drug-resistant TB • Conventional Methods: • Grow TB in culture • Assess for growth (resistant) or absence of growth (susceptible) at 4 weeks

  25. Nucleic Acid Amplification Tests • Amplify nucleic acid segments specific for M. tuberculosis • Rapid: Results in 24-48 hours • Commercially Available: • Mycobacterium Tuberculosis Direct (MTD) • AmplicorM.Tb Test (Amplicor) • Cepheid GeneXpert MTB Rif • Cepheid GeneXpert • MTB Rif

  26. Case 2 • 66 yo homeless man with abnormal chest xray, weight loss, chronic cough • Smear positive for AFB • HIV-infected • Treatment? • 4 drug regimen: Rifampin, INH, PZA, Ethambutol • May stop PZA after 2 months • May stop Ethambutol if no resistance • For 6 to 9 months total duration

  27. TB and HIV infection • Difficult to diagnosis (low amount of TB) • Drug-drug interactions • Immune reconstitution inflammatory syndrome (IRIS) • Delay antiretroviral therapy until on TB treatment • If CD4 < 50 delay 2 weeks • If CD4 > 50 and stable, delay 8 weeks • Monitor for worsening • Consider addition of steroids

  28. New developments in TB • Ongoing search for point of care test • Urine LAM: antigen detection; potentially useful, in HIV-infected patients with CD4 <50 • Reports of ‘Totally Drug Resistant’ TB • Finally, new drugs for drug-resistant TB • Bedaquiline (Sirturo)– FDA approved Dec 2012 for MDR-TB • Delaminid – phase III trial

  29. Olive View Inpatient TB Unit TB Unit • 15 beds (10 staffed currently) • Patients must be stable with lab-confirmed TB • Categories of patients • Infectious, need prolonged isolation • Drug resistant TB requiring special management • TB drug adverse reactions • Public health detention

  30. Group questions & dilemmas

  31. Group 1 The patient has HIV infection but his TB skin test is negative What are 3 possible explanations?

  32. Group 2 A patient has been started on TB medicines. He initially gets better and then gets worse. What are 3 possible explanations?

  33. Group 3 • Name 3 groups that are high risk for TB • Describe 3 ways the risk for TB might be decreased in those groups?

  34. Group 4 • TB is a public health condition that gets reported to the health department. • Name 3 other “reportable” conditions • Describe what the health department does with that information

  35. Thank you

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