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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 September 2014 African-American HIV University 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 STD Guidelines group Dr. Klausner is a board member of YTH, Inc, non-profit Dr. Klausner is medical advisor for Healthvana.com • In the past 12 months, Dr. Klausner has received: – Travel support for meeting coordination and speaking from Standard Diagnostics, Inc. – Research funding or donated supplies from the NIH, CDC, Hologic, Inc., Alere, Inc., Chembio, Inc. Cepheid, Standard Diagnostics, Inc., and MedMira, Inc. [email protected] Objectives: TB Update 1) 2) 3) 4) Review of TB epidemiology & pathogenesis New tests and treatment for latent TB Diagnosis of active TB TB puzzles TB Frequency Reported TB Cases, U.S. 1982-2012 CDC MMWR 2010 Where is TB? Global Tuberculosis Control 2011; WHO 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 • 1.3 million TB deaths / year Tuberculosis Cases in Foreign-born and U.S.-born Persons by Race/Ethnicity: California, 2010 Credit: CDPH TB Control Program Natural History of TB Exposure Latent Infection • Asymptomatic • Not Infectious 90% Infection 10% Close Aerosol Contact With an Infectious Case X Active TB disease 10% lifetime risk 5% first 2 years after infection • Treat latent TB to prevent active TB Relative Risk for Developing Active TB Risk Factor Approximate Risk by Risk Factors HIV/AIDS 170 * Lung Disease due to Silica 30 Immunosuppression 10-15 Cancer 10-15 Hemophilia 5-10 Kidney failure 10-15 Malnutrition 2-4 Diabetes 2-4 Smoking 2 Targeted Tuberculin Testing and Treatment of Latent TB Infection CDC, MMWR June 2000 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 Latent TB Infection 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 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 * TB Skin Test 48-72 hrs • • • • Interpretation depends on risk factors Reader error No immune response in some pts Reactivity Quantiferon TB Testing • Measures immune response to TB antigens • Similar principle to TST – Uses TB-specific antigens – Not affected by BCG vaccination (specific) TST and Quantiferon Presentation of mycobacterial antigens IFN- TNF- IL-8, etc. Tuberculin skin test IFN- Antigen presenting cell Memory T-cell Andersen P, et al. Lancet 2000;356:1099 TNF- IL-8, etc. IGRA Case 1 • 32 year old health care worker with positive Quantiferon Test • 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/ rifapentine weekly Treatment of latent TB in patients with HIV infection • 6 months of isoniazid • Some recommend 36 months • ? Perhaps until CD4 > 500 Active TB Exposure Latent TB Infection Active TB Infection Symptomatic Death Treatment TB Diagnostic Tests • Smear microscopy (sputum, tissue) • Mycobacterial Culture (sputum, blood, tissue) • Nucleic Acid Amplification Tests (sputum, tissue) 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 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 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 Nucleic Acid Amplification Tests – Amplify nucleic acid segments specific for M. tuberculosis – Rapid: Results in 24-48 hours – Commercially Available: • Mycobacterium Tuberculosis Direct (MTD) • Amplicor M.Tb Test (Amplicor) • Cepheid GeneXpert MTB Rif Cepheid GeneXpert MTB Rif 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 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 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 Olive View Inpatient TB Unit TB Unit 15 beds (10 staffed currently) Patients must be stable with labconfirmed TB Categories of patients • Infectious, need prolonged isolation • Drug resistant TB requiring special management • TB drug adverse reactions • Public health detention Group questions & dilemmas Group 1 The patient has HIV infection but his TB skin test is negative What are 3 possible explanations? Group 2 A patient has been started on TB medicines. He initially gets better and then gets worse. What are 3 possible explanations? Group 3 • Name 3 groups that are high risk for TB • Describe 3 ways the risk for TB might be decreased in those groups? 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 Thank you