Didactic Series. Latent TB Infection in HIV Infection

Transcription

1 Didactic Series Latent TB Infection in HIV Infection Jacqueline Peterson Tulsky, MD UCSF Positive Health Program at SFGH Medical Director SF, North Coast and East Bay AETC January 8, 2015 ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this educational activity for a maximum of one credit per hour AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. 1

2 Learning Objectives Identify principles of TB screening in HIV infected patients Discuss treatment and prevention recommendations Review cases of HIV and LTBI patients 2

3 A patient for TB screening AC is 52 yo Af-Am man 10 yr hx of HIV+ on ART. CD4 270, nadir 120, VL UD. Major co-morbidity is HAND, Hep C and crack cocaine dependence (daily user). New to you, 2006 QFT +, no hx of Rx for LTBI. No symptoms of TB. 1. What to do about his QFT+ hx? a) It was over 2 years ago, no eval needed b) No symptoms, so CXR only c) Place a TB Skin Test (TST) d) Other approach 3

4 US 2013 TB Cases MMWR Annual TB Report May 2014 Total cases of TB 9,588 CA, FL, NY, TX > 50% all cases Foreign-born 64.6% TB and HIV+ 6.8% 5

5 Why the HIV/TB Association? HIV induced immune defects => decreased TB control systems 5-8%/year activation instead of 10% over a lifetime Its all about the T-cells! Latent TB Infection (LTBI) in dormant phase Lower T-cells (particularly CD4), empower the Mycobacterium Lower CD4 cells also dis-empower TB screening 6

6 HIV-TB Screening Issues TST/IGRA/CXR/symptom review Repeating LTBI tests in HIV patients Screening prior positives LTBI management after contact to a case 7

7 A word about BCG Live vaccine Bacillus of Calmette and Guerin (BCG) Attenuated Mycobacterium Bovis -- Not ROUTINELY recommended for known HIV+ Evaluation of TST reactions in persons vaccinated with BCG should be interpreted using the same criteria for those not BCGvaccinated 8

8 Pearls about TB Skin Test (TST) Read at hours, but positive can persist for days > 5mm of induration is positive FOR Recent contacts Immune compromised > 10mm if not high risk Don t repeat if positive 9

9 Blood Tests for TB Screening Interferon γ releasing assays (IGRAs) Whole blood (5cc) test Measures immune reactivity to M. tb QuantiFERON Gold-In Tube(QFT-GIT) and T- spot both FDA approved Does not tell LATENT from ACTIVE TB

10 How Quantiferon Is Performed Stage 1 Whole Blood Culture Nil Control Avian PPD Tb PPD Mitogen Control Heparinized whole blood Transfer undiluted whole blood into wells of a culture plate and add antigens Culture overnight at 37 o C TB infected individuals respond by secreting IFN-γ Stage 2 IFN-gamma ELISA Harvest plasma from above settled cells and incubate 60 min in Sandwich ELISA COLOR TMB Wash, add substrate, incubate 30 min then stop reaction IFN-γ IU/ml OD 450nm Standard Curve Measure OD, determine IFN-γ levels and interpret test

11 Interpreting QFT Gold IN-Tube Positive or Negative or Indeterminate Negative : M. TB infection NOT likely Nil = 0.18 TB Antigen-NIL = 0.05 Mitogen-Nil = 7.33 Positive would have TB Antigen-Nil >0.35 Indeterminate is uninterpretable

12 IGRAs in 2014 Can be used like TST for screening Distinguishes Mtb, Mkansasii, Mbovis Help in BCG vaccinated (Mbovis) persons Flip/Flop results may be due to waning More specific than sensitive (false negatives) Cost issues remain

13 Summary LTBI Testing 2014 Use screening test that is most available Positives = positive Indeterminate can t be interpreted If test is negative and it matters a lot Repeat screening with other type of test and Repeat TB screening when CD4 goes over 200 cells 14

14 Treatment for LTBI Traditional INH 5mg/kg (max 300mg) daily or 900mg 2 x a week Other options - Rifampin/rifabutin daily for 4 months 3 months (12 doses) by DOT in HIV* INH 15mg/kg (max 900mg) weekly AND Rifapentine wgt-based dose (max 900mg) weekly * Not for Pregnant or expect to get pregnant; children <2yrs 15

15 Screening TB that is HIV Specific Blood cultures for M. tb higher yield in HIV CD4 count <100, get single mycobacterial culture when febrile Extra-pulmonary TB common, 25-40% multi-site infection Get CXR and sputum AFB cultures even if extra-pulmonary site found 16

16 Ongoing Screening for LTBI in HIV HIV program protocols ---TB screening on entry Repeat based on risk of exposure Disease-based (HIV) screening -- Prior to starting ART Repeat if CD4 rises above 200 cells/ml 17

17 A patient for TB screening AC is 52 yo Af-Am man 10 yr hx of HIV+ on ART. CD4 270, nadir 120, VL UD. Major co-morbidity is HAND, Hep C and crack cocaine dependence (daily user). New to you, 2006 QFT +, no hx of Rx for LTBI. No symptoms of TB. 1. What to do about his QFT+ hx? If CXR normal, would offer treatment for LTBI. INH 900mg 2 x a week by DOT chosen. 18

18 When is Empiric Rx of LTBI Appropriate? Q. What is the Window Period for LTBI For contacts to a TB case - 3 months between initial LTBI negative and final screening Q. Why does it matter more in HIV+? Hyper rapid evolution to active TB after exposure Ex: AIDS residential program outbreak 37% exposed became active TB in 15 weeks 19

19 Summary LTBI Treatment R/O active TB then start INH or INH/Rifapentine in high risk pts HIV + or contacts to a case if HIV A reason to test is a reason to treat, so test thoughtfully INH in pregnancy, HIV+ or high risk pt Add B mg daily for neuropathy Close monitoring of symptoms and signs hepatitis Lower risk pts, wait 2-3 months post partum 20

20 HIV TB/HIV Summary Makes it harder to screen for LTBI TB more likely to activate, higher TB mortality Rescreen after starting ART or CD4 >200 cells Screen all HIV patients for TB and all TB patients for HIV LTBI Rx: INH 9 months or Rif 4 months INH+Rifapentine 12 weekly doses by DOT 21

21 A patient for TB screening AC started INH 2 x a week DOT. At about week 10, he was complaining of numbness in his right fingers and toes on the tips. What is your approach? How to evaluate and what intervention?? At 4 months, his monthly ALT was 3 x normal. Asymptomatic, denies ETOH or higher dose acetaminophen. Now what? 22

22 Resources TB Warmline or (415) Mon-Fri leave message AETC National Resource Center AIDSinfo: HIV/TB Treatment Guidelines HIV InSite TB Center 23