Screening and management of latent TB Infection Gerry Davies

Transcription

1 Screening and management of latent TB Infection Gerry Davies Reader in Infection Pharmacology Institutes of Infection and Global Health & Translational Medicine HIV Scientific Meeting Liverpool 21st July 2017

2 Overview What is the risk of TB in HIV+ people? How do we test for latent TB infection (LTBI)? Who should be treated for LTBI? What are the best treatments for LTBI? What does recent guidance say?

3 2 billion latent infections 9.6 million new cases/yr 1.5 million deaths /yr 26% of avoidable adult deaths in developing world

4 Pathogenesis of tuberculosis Transmission Primary Infection Latent Infection HIV TNFα IFNγ inos Vitamin D Immune immaturity/ senescence Active Disease

5 Risk of TB in HIV HIV prevalence Incidence Rate Ratio <0.1% 36.7 ( ) 0.1-1% 26.7 ( ) >1% 20.6 ( ) Annex 2, WHO Report 2009

6 Risk of TB in HIV Lawn SD 2005 AIDS 19 (11) :

7 Risk of TB after ART Lawn SD 2005 AIDS 19 (18) :

8 Global Epidemiology % in 22 high burden countries 30% in India & China

9 Risk by Ethnicity & Birthplace in UK

10 Tuberculin skin testing (TST) Distribution of Reaction Sizes to 5 TU Tuberculin PPD-S in 5,544 Tuberculosis Patients, United States Per cent reacting In d u ra tio n(m ) Edwards LB, et al. Am Rev Respir Dis 1969;99(4, part 2 of 2):1-132

11 Tuberculin skin testing (TST) N=991 HIV + HIV - 25 vs 3% <3 mm Cobelens FG 2006 Clin Inf Dis 43:634-9

12 Interferon-γ release assays (IGRA)

13 IGRA in HIV+ : Active Disease Overall Sn/Sp was 76%/61% for ELISPOT & 60%/52% for QFT-IT Metcalfe J et al JID 204 Suppl 4:S1120-9

14 IGRA in HIV+ : Predicting future disease Rangaka M et al Lancet ID 2011

15 Courtesy of Hanif Esmail

16 Courtesy of Hanif Esmail

17 Courtesy of Hanif Esmail

18 Chemoprophylaxis : HIV-negative

19 Chemoprophylaxis : HIV-positive

20 Duration of protection N=1329 HR 0.63 ( ) Rangaka MX Lancet :

21 Relative impact of ART and IPT Early vs Deferred ART HR 0.56 ( ) IPT vs No IPT HR HR 0.65 ( ) TEMPRANO ANRS NEJM :808

22 Prolonged Chemoprophylaxis HR 0.50 for TB in those on ART HR 0.57 for continuous vs 6mo IPT p=0.047 Samandari T Lancet : 1588

23 Mass Chemoprophylaxis Churchyard GJ 2014 NEJM 370 : 301

24 Alternatives to Isoniazid Stagg HR Ann Int Med : 419

25 Alternatives to Isoniazid Stagg HR Ann Int Med : 419

26 3HP : PREVENT-TB/TBTC Study 26 Sterling TR AIDS : 1607

27 BHIVA Guidelines 2011 Alternatives for treating latent TB: isoniazid for 6 months [201]; [A11] rifampicin with isoniazid for 3 months given daily in standard doses or twice a week using 900 mg isoniazid; [BI] rifampicin for 4 months. [BIII]

28 WHO Guidelines 2011 Use clinical algorithm to screen for active tuberculosis (Strong recommendation, moderate quality evidence) Offer at least 6 months IPT to those with positive or unknown TST status (Strong recommendation, high quality evidence) Offer at least 36 months IPT to those with positive or unknown TST status (Conditional recommendation, moderate quality evidence) Irrespective of Stage, CD4, ART, previous TB treatment, pregnancy TST not a requirement for initiating IPT (Strong recommendation, moderate quality evidence)

29 WHO Guidelines 2016 Systematic testing and treatment of LTBI should be performed in people living with HIV (Strong recommendation, low to very low quality of evidence) Use symptom screening and chest radiography if efforts are intended also for active TB case finding (Strong recommendation, low quality of evidence) Either TST or IGRA can be used to test for LTBI in high-income and upper middle-income countries with estimated TB incidence less than 100 per (Strong recommendation, low quality of evidence). IGRA should not replace TST in low-income and other middle-income countries.(strong recommendation, very low quality of evidence) Treatment options recommended for LTBI include: 6-month isoniazid, or 9-month isoniazid, or 3-month regimen of weekly rifapentine plus isoniazid, or 3 4 months isoniazid plus rifampicin, or 3 4 months rifampicin alone. (Strong recommendation, moderate to high quality of evidence).

30 NICE Guidelines 2016 (NG33 & QS141) Adults aged under 65 years who are diagnosed with HIV, are tested for latent tuberculosis (TB) infection Risk assessment based on degree of immunocompromise and risk factors such as country of origin and contact In severe immunocompromise (CD4 <200) perform TST AND IGRA If either test is positive (for Mantoux, this is an induration of 5 mm or larger, regardless of BCG history), assess for active TB. If this assessment is negative, offer them treatment for latent TB infection 3HR or 6H with pyridoxine Monitor for drug-induced liver injury (if baseline LFTs abnormal or other risk factors)

31 Summary LTBI poses significant risks to HIV+ people Guidelines recommend aggressive screening and treatment Diagnostic tests imperfect but IGRA now standard in UK Risk stratification still based on clinical and epidemiological assessment Shorter rifamycin-based regimens may be advantageous Consideration of drug interactions and toxicity monitoring Feasibility and cost-effectiveness