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 and North Coast AETC March 13, 2014 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 Explain the importance of TB prevention in HIV Apply TB screening recommendations to HIV patients, including BCG considerations Discuss treatment options in HIV and LTBI 2

3 Mary M is 28yrs old woman born in Peru and diagnosed HIV+ 4 weeks ago. Seeing you in first primary care appointment. CD4 189, no symptoms. She has no concerns about TB because of a TB vaccine as a child. 1. Tell us about screening her for TB? Live mic or chat box about your practice 2. If BCG hx, how to screen her? Any thoughts from your experience? 3

4 On a slide, it looks so innocuous Tubercle bacilli w/ Ziehl-Neilsen stain, most labs now screen w/ florescent stains and dark field microscopy

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6 Worldwide Epidemiology TB is following the HIV epidemic As HIV epidemic matures and people become more immunocompromised, TB incidence rises Nunn, Nature Reviews,

7 US 2012 TB Cases MMWR Annual TB Report March, 2013 Total cases of TB 9,951 CA, FL, NY, TX > 50% all cases Foreign-born 60.0% TB and HIV+ 7.7% 7

8 Why the HIV/TB Association? HIV induced immune defects => decreased TB control systems 5-8%/year activation instead of 10% over a lifetime It s 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 8

9 TB Incidence Increases as CD4 CD4 (Ct/ml) Drops > < TB incidence/ 100 person-years Badri M, Wilson D, Wood R. Lancet, 2002;359 9

10 HIV-TB Screening Issues Choosing and interpreting LTBI screening tests Repeating LTBI tests in HIV patients CD4 guided testing Clinic policy on frequency of testing Screening prior positives LTBI management after contact to a case 10

11 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 11

12 TB Skin Test (TST) for TB Screening Place and read at hours > 5mm of induration is positive FOR Recent contacts Immune compromised Non high risk > 10mm Can be read after 72 hrs IF positive Should not be repeated if positive 12

13 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

14 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

15 Interpreting Quantiferon-TB Gold IN-Tube Positive or Negative or Indeterminate Negative Example: M. Tuberculosis infection NOT likely Nil = 0.18 TB Antigen-NIL = 0.05 Mitogen-Nil = 7.33 Positive would have TB Antigen-Nil >0.35

16 IGRAs Can be used like TST for screening Response unique to Mtb, Mkansasii, Mbovis Useful in BCG vaccinated (Mbovis) recipients No confirmatory test for LTBI More specific than sensitive (false negatives) Cost issues not well explored

17 IGRAs compared to TSTs In vitro Multiple antigens No boosting 1 patient visit Minimal interreader variability Results in 1 day Stimulate w/ 12 hrs In vivo Single antigen Boosting 2 patient visits Inter-reader variability Results in 2-3 days Read in hrs

18 IGRAs for TB Screening Sensitivity suboptimal, but as good as TST Elispot-6 (T-spot) best at 93% Pooled specificity better QFT-GIT up to 98% T-spot 92% Discordance with HIV + pts between IGRAs and TST Frequent (6-12%) Unexplained Menzies D, Pai M, Comstock G - Annals Int Med 2007;146:

19 Summary LTBI Testing 2012 Use screening test that is most available to you Positives are 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 19

20 Traditional 9 months Treatment for LTBI INH 5mg/kg (max 300mg) daily Other variations - Rifampin daily for 4 months Brand New - 3 months (12 doses) * INH 15mg/kg (max 900mg) weekly plus Rifapentine wgt-based dosing (max 900mg) weekly * Not for HIV+ on ARVs; Pregnant or expect to get pregnant; children <2yrs 20

21 Screening TB that is HIV Specific Blood cultures for M. tb more often positive with HIV CD4 count <100, yield justifies single mycobacterial culture when febrile High frequency of extra-pulmonary TB (25-40% multi-site infection) Get CXR and sputum AFB cultures even if extra-pulmonary site found 21

22 Ongoing Screening for LTBI in HIV HIV program protocols - TB screening on entry - Repeat based on risk of exposure Disease-based (HIV) screening - Repeat prior to starting ART - Repeat if CD4 rises above 200 cells/ml, (usually due to ART) 22

23 Should you Re-treat in HIV/LTBI? Q. Got 6 months INH before known HIV positive? If clear CXR and adherent to 6 months No Q. Previously LTBI positive and treated, now re-exposure? If high risk by various parameters Yes 23

24 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 24

25 Summary LTBI Treatment Principles 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 okay in pregnancy if 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 25

26 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 >200cells Screen all HIV patients for TB and all TB patients for HIV LTBI Rx: INH 9 months or INH+Rifapentine 12 weekly doses (in selected patients) 26

27 References MMWR TB stats: 3/2/13; IGRAs: 6/25/10 v59; Rx LTBI: 12/9/11 V60 html 27

28 Resources TB Warmline or (415) Mon-Fri leave message AETC National Resource Center AIDSinfo: HIV/TB Treatment Guidelines HIV InSite 28