TB/HIV and other immunosuppressive states

Transcription

1 TB/HIV and other immunosuppressive states Sylvia LaCourse MD, MPH Department of Medicine, Division of Allergy & Infectious Disease TB Clinical Intensive Seattle, WA June 14 15, 2018 Roadmap for today s talk TB in people living with HIV (PLHIV) Risk of LTBI >TB Clinical manifestations TB treatment (ART/TB medication interactions) Immune reconstitution inflammatory syndrome (IRIS) LTBI treatment TB and other immunosuppressive states Solid organ (and hematopoietic stem cell) transplant Immunosuppressive/TB medication interactions TB and biologics (TNF alpha inhibitors) 1

2 Latent TB (LTBI) and active TB Small, NEJM 2001 Latent TB (LTBI) and active TB HIV 10% over lifetime greatest risk in 1st 2 years Small, NEJM

3 Latent TB (LTBI) and active TB HIV 10% over lifetime greatest risk in 1st 2 years HIV+ 10% per year Small, NEJM 2001 HIV kills TB specific CD4 cells Impairs macrophage activation Fewer lung homing CD4 cells Defective granuloma formation Loss of control of infection Geldmacher, Curr Opin HIV AIDS,

4 MTb infec on TB disease Lawn Clin Dev Immunology 2011 MTb infec on TB disease ART (+ TPT) Although ART significantly decreases TB risk, still much higher than among HIV Lawn, Clin Dev Immunology

5 Clinical Manifestations of TB in HIV+ Influenced by degree of immunosuppression Most still present with pulmonary disease Upper lobe fibronodular infiltrates +/ cavitation Advanced HIV (CD4 < 200) Can have pulmonary TB (+ AFB/cx) w/ nml CXR Often smear negative >paucibacillary Extrapulmonary/disseminated disease common Lymphadenitis, pleuritic, pericarditis, meningitis, sepsis Important to evaluate for PTB in HIV+ with EPTB DHHS 2017 Question 1 Which of the following is true? A. HIV significantly increases the risk of progression from LTBI to TB B. ART significantly decreases the risk of TB among HIV+ C. Once on ART, risk of TB among HIV+ is similar to HIV D. Most common presentation of TB among HIV+ is extrapulmonary E. A & B F. C & D 5

6 TB treatment in HIV+ Anti TB regimen generally the same for non HIV Initial phase: INH, RIF, PZA, EMB x 2 months Continuation phase: INH, RIF x 4 months Extended to 7 months if initial CXR + cavitation & Cx + at end of 2 months of initial phase Important exceptions for HIV+: Initial phase: INH, RIF, PZA, EMB given daily Continuation phase: INH, RIF given daily (or 3 x week) If no ART during TB tx: extend to 7 months Culture negative pulm TB: 6 months total treatment (vs. 4 months HIV ) ATS, CDC, IDSA CID 2016 DHHS 2017 TB treatment in HIV+ Drug(s) Duration Interval Comment Initial phase INH, RIF, PZA, EMB 2 months Daily Recommended Continuation phase INH/RIF 4 months Daily Recommended INH/RIF 4 months 3 x week Alternative For HIV+ both initial phase and INH/RIF 4 continuous months Twice phase weekly are given daily Not recommended for HIV+ INH/RPT 4 months Once weekly Contraindicated ATS, CDC, IDSA CID 2016 DHHS

7 Basic Principles in ART and TB treatment Rifamycin based TB treatment is cornerstone of effective TB treatment Efavirenz based ART preferred Most drug drug interactions due to Rifampin Potent inducer of P450 enzyme 3A sometimes requires ART dose adjust (typically dose) Rifabutin less potent inducer Sometimes requires rifabutin dose adjust ( or dose) Important: if ART dc d, rifabutin may be subtherapeutic DHHS 2017 CDC 2013 ATS, CDC, IDSA CID 2016 Timing of ART and TB treatment ART is recommended for all HIV+ with TB For ART naïve CD4 < 50 start ART within 2 weeks CD4 > 50 start by 8 12 weeks Exception: TB meningitis start > 8 weeks (to reduce risk of IRIS) If already on ART, continue ART May require medication adjustment DHHS 2017 ATS, CDC, IDSA CID

8 ARV ARV dose change RIF dose change Comments NNRTIs Efavirenz None; some 800mg if >50kg No change Preferred Regimen (still!) Nevirapine Rilpivirine Etravirine NRTIs Tenofovir disoproxil fumarate (TDF) Tenofovir alafenamide (TAF) ART and RIF recommended dose adjustments lead in dose 200 mg No change twice daily, continue as maintenance dose Contraindicated None None Preferred Unknown Avoid lead in 200mg once daily, assoc w/ virologic failure Consider therapeutic drug monitoring. Rarely used in US Significant decrease in Rilpivirine TAF concentration decreased in healthy volunteers (but intracellular concentrations still higher than TDF) CROI 2018 RIF decreases NNRTI (and some NRTI) levels DHHS 2017 CDC 2013 ATS, CDC, IDSA CID 2016 CROI 2018 ART and RIF recommended dose adjustments (cont.) Integrase inhibitors Raltegravir Raltegravir to 800 mg twice daily Dolutegravir Dolutegravir to 50 mg twice daily ARV dose change RIF dose change Comments No change No change Raltegravir trough concentrations still decreased, follow VL carefully follow VL carefully Bictegravir Bictegravir should not be used together Decrease in Bictegravir even when given BID (Custodia, CROI 2018) Elvitegravir, Stribild or Genvoya and rifampin should cobicistat, TDF or TAF, not be used together and emtricitabine (Stribild or Genvoya) CCR 5 receptor antagonists Maraviroc Maraviroc to 600 No change mg twice daily Marked decrease in elvitegravir and cobicistat concentrations predicted based on metabolic pathways of these drugs Use with caution, as there is no reported clinical experience with increased dose of maraviroc with rifampin RIF decreases INSTI levels DHHS 2017 CDC 2013 ATS, CDC, IDSA CID

9 ART and RIF recommended dose adjustments (cont.) ARV dose change RIF dose change Comments Protease inhibitors Lopinavir/ritonavir (Kaletra ) Super boosted lopinavir/ritonavir (Kaletra ) Atazanavir (single agent or ritonavir boosted) Darunavir/r Fosamprenavir/r Saquinavir/r Lopinavir 800 mg plus No change ritonavir 200 mg twice daily (double dose) Lopinavir 400 mg plus No change ritonavir 400 mg twice daily (super boosting) Contraindicated Hepatotoxicity in healthy volunteers Better tolerated among HIV+ already on LPV/r Hepatotoxicity in healthy volunteers Significant decrease in PIs, Increased PI doses associated +/ hepatotoxicity For PIs RFB preferred DHHS 2017 CDC 2013 ATS, CDC, IDSA CID 2016 ARV ARV dose change RFB dose change Comments NNRTIs Efavirenz No change 600 mg (daily or RIF preferred thrice weekly) Nevirapine No change No change Etravirine No change No change Conc of both decreased Rilpivirine Contraindicated Significant decrease in Rilpivirine Protease inhibitors Atazanavir (single agent or ritonavir boosted) ART and RFB recommended dose adjustments No change 150 mg daily No pub clinical experience Monitor closely for potential rifabutin toxicity uveitis, hepatotoxicity, and neutropenia Darunavir/r Fosamprenavir/r Saquinavir/r Lopinavir/ritonavir (Kaletra ) No change 150 mg daily Monitor closely for potential rifabutin toxicity uveitis, hepatotoxicity, and neutropenia No change 150 mg daily Hepatotoxicity in healthy volunteers Better tolerated among HIV+ already on LPV/r RFB levels decreased with EFV, increased with PIs DHHS 2017 CDC 2013 ATS, CDC, IDSA CID

10 ART and RFB recommended dose adjustments (cont.) ARV dose change RFB dose change Comments Integrase inhibitors Raltegravir No change No change RAL conc Dolutegravir No change No change DOL conc Elvitegravir, cobicistat, tenofovir, and emtricitabine (Stribild ) CCR 5 receptor antagonists Stribild (or Genvoya) and rifabutin should not be used together Marked elvitegravir, cobicistat conc Marked rifabutin Maraviroc No change No change No clinical experience; a significant interaction is unlikely, but this has not yet been studied INSTI levels increased with RFB DHHS 2017 CDC 2013 ATS, CDC, IDSA CID 2016 ART and TB treatment: Overlapping toxicities Adverse effect ART Anti TB therapy Gastrointestinal AZT, ddi, PIs R,I,P, ethionamide, PAS, Clofazamine, linezolid Hepatotoxicity NVP, EFV, PIs, NRTIs R,I,P, ethionamide, quinolones, PAS Neuropathy D4T, ddi I, ethionamide, cycloserine, linezolid Renal dysfunction TDF Aminoglycosides and capreomycin Neuropsychiatric Upon EFVre challenge Cycloserine, >90% patients ethionamide, quinolones, Rash INH tolerate medications without a NVP, EFV, ABC R,I,P,E, streptomycin, quinolones, PSA, recurrence of the adverse clofzamine effect Cytopenia AZT, 3TC R,I, linezolid, rifabutin Cardiac conduction PIs Bedaquiline, quinolone, clofazamine Pancreatitis D4T, ddi Linezolid Lactic acidosis D4T, ddi Linezolid ATS, Am J Respir Crit Care Med, 2006 Lawn, BMC Medicine,

11 Question 2 Which of the following are true in the management of TB in an HIV+ individual? A. Rifamycins should be avoided due to multiple ART and anti TB medication interactions B. In an ART naïve HIV+ patient, ART initiation should be deferred until after TB treatment is completed to avoid drug interactions C. Integrase inhibitors require dose adjustment (increase) when co administered with rifampin D. Rifampin requires dose adjustment when co administered with Efavirenz Immune Reconstitution Inflammatory Syndrome: IRIS IRIS: collection of inflammatory disorders Paradoxical worsening of preexisting infectious processes Assoc w/ immune recovery following ART initiation Risk Factors: CD4 and VL pre ART, short time between TB tx and ART initiation, but TB IRIS can occur at CD4 >200 Meintjes, Lancet ID,

12 Immune Reconstitution Inflammatory Syndrome: IRIS IRIS: collection of inflammatory disorders Paradoxical worsening of preexisting infectious processes Assoc w/ immune recovery following ART initiation Risk Factors: CD4 and VL pre ART, short time between TB tx and ART initiation, but TB IRIS can occur at CD4 >200 Meintjes, Lancet ID, 2008 Immune Reconstitution Inflammatory Syndrome: IRIS IRIS: collection of inflammatory disorders Paradoxical worsening of preexisting infectious processes Assoc w/ immune recovery following ART initiation Risk Factors: CD4 and VL pre ART, short time between TB tx and ART initiation, but TB IRIS can occur at CD4 >200 Meintjes, Lancet ID,

13 TB IRIS: Clinical manifestations Pulmonary TB Sx: fever, malaise, weight loss, and worsening resp sx Worsening CXR: new parenchymal opacities and progressive intrathoracic lymph node Extrapulmonary TB Worsening lymphadenitis, new pleural effusions, intracranial tuberculomas, worsening of meningitis or radiculomyelopathy cold abscesses Meintjes, Lancet ID, 2008 TB IRIS: Treatment Continue ART unless life threatening Steroids RCT 4 wks prednisone vs. placebo for TB IRIS symptoms, improved CXR, hospitaliza on NSAIDS Recent trials: Empiric prednisone during 1 st 4 wks of ART risk of paradoxical TB IRIS by 30% Meintjes CROI 2017 Meintjes AIDS,

14 Question 3a 23 y/o Ethiopian F presents with weight, loss, fever, and cough. CXR shows RUL opacity. Sputum smear is neg. RIPE started due to concerns for PTB (NAAT return Mtb+). As part of her TB w/u she is tested for HIV and found to be positive w/ CD4 48. Which of the following are true? A. ART should be initiated within 2 weeks B. ART should be initiated after she has completed initial phase of TB treatment C. ART should be initiated after she has completed continuation phase of TB treatment D. TB treatment should be stopped until after she has initiated ART and her VL is undetectable Question 3b She initiates ART treatment and continues w/ RIPE. After 2 weeks she develops fever, and her CXR now shows worsening pulmonary infiltrates You should A. Stop ART B. Collect sputum looking for MDR TB and add moxifloxacin and amikacin while waiting C. Stop ART therapy and start prednisone D. Continue anti TB tx and ART, evaluate the patient for other infections, failed TB therapy and drug toxicity and consider starting prednisone 14

15 TB and HIV LTBI and HIV 15

16 Drug(s) Duration Comment Isoniazid 9 months Recommended Isoniazid + Rifapentine 3 months OK if NO ART or EFV or RAL based ART. Drug interactions : TAF, DOL Rifampin 4 months Drug interactions May required dose adjustment Rifabutin 4 months Drug interactions May required dose adjustment Rifampin + Pyrazinamide LTBI treatment in HIV+ 2 months Contraindicated Recent trials: 1 INH/RPT: not inferior to 9 INH Swindells CROI 2018 BRIEF TB/ACTG5279 INH pregnancy vs. postpartum : similar maternal safety, higher risk of fetal and pregnancy outcomes Gupta CROI 2018 IMPAACT 1078 Question 4 45 year old HIV+ male HCW well controlled on ART (FTC/TAF + DOL) recently converted his TST after a medical mission trip in Haiti. TB symptom screen and CXR are negative. He s heard about a new short course LTBI treatment that you only have to take once a week and wants to know what his options are. Based on CDC/ATS/DHHS guidelines you recommend: A. INH x 9 months (daily) B. RIF x 4 months (daily) C. RIF + PZA x 2 months (daily) D. INH + RPT x 3 months (weekly) 16

17 Shifting gears to shift/ TB and Solid Organ Transplant (SOT) TB risk x higher than general pop Incidence in low prevalence regions % Higher mortality 6 22% (vs <5% for TB in general US) Horne CID 2013, Aguado CID

18 TB and SOT: things to consider Reactivation of LTBI in setting of immunosuppression Recurrence of previously treated TB Drug drug interactions Baseline organ dysfunction Donor derived infections Unrecognized active TB Reactivation of LTBI in the graft Horne CID 2013 Aguado CID 2009 TB and SOT: risk factors Transplant related immunosuppression Standard TB risk factors Underlying medical condition Aguado CID

19 TB and SOT: risk factors Transplant related immunosuppression Standard TB risk factors Underlying medical condition Aguado CID 2009 TB and SOT: clinical manifestations Atypical presentations Non specific sx (fever, weight loss, night sweats) Extrapulmonary/disseminated more common Classic upper lobe infiltrate / cavities less likely Diagnostic delays Horne CID 2013, Aguado CID

20 TB and SOT: screening Recipient prior to transplant TST or IGRA However many SOT recipients who develop TB had neg TST/IGRA prior to transplant Chest imaging (CXR, +/ CT) Epidemiologic risk assessment Donors Living donors LTBI screening (and treatment) Deceased donors Moderate to high TB risk: imaging (consider CT) + AFB smear (+NAAT/Culture) donor with untreated LTBI, recent exposure, radiographic evidence of untreated TB > LTBI treatment for recipient Horne CID 2013, Aguado CID 2009 LTBI and SOT: treatment Timing: pre or post transplant? Horne CID

21 LTBI and SOT: treatment Choice of regimen INH RIF INH/RPT Best studied well tolerated preliver txp Shorter duration Shorter duration Need for further study: RBT, FLQ Longer duration Hepatotoxicity post txp P450 inducer immunosuppressive agents; rejection allograft loss Doesn t avoid INH adverse effects / rifamycin drug interactions Horne CID 2013, Aguado CID 2009 LTBI/TB treatment and SOT: important drug interactions Rifampicin reduces levels of many immunosuppressive agents Corticosteroids Calcineurin inhibitors: tacrolimus, cyclosporine mtors (mammalian target of rapamycins): rapamycin (sirolimus), everolimus Reduced levels immunosuppressant levels increase risk of graft rejection Need to increase dose of calcineurin inhibitors 3 5x, closely monitor levels Aguado CID

22 Question 5 49 y/o US born female underwent double lung transplant for bronchiolitis obliterans. Bronchoscopy POD 1 to ensure good anastomosis. BAL: AFB, Cx + MTB. Chest CT +small LUL nodules. Donor: 21 y/o Guatemalan immigrant with faint UL opacity, scattered midlung calcifications. Which of the following are true? A. Her immunosuppression medications should be decreased to reduce her risk of TB complications B. TB treatment should be delayed until she requires less immunosuppression Horne CID 2013, Winthrop Am J Transplant 2004 C. RIPE therapy should be initiated with reduced RIF dose to avoid drugdrug interactions with her immunosuppressants D. TB treatment should be initiated, and she will likely need an increase in her immunosuppressant dosing with close monitoring of drug levels to avoid graft rejection TB and Hematopoietic Stem Cell Transplant (HSCT) TB risk 10 40x higher than general population ~ 10X less common than among SOT (due to transient immunosuppression) Highest risk among allogenic transplants Primarily due to LTBI reactivation Aguado Microbio Spectrum

23 TB and Hematopoietic Stem Cell Transplant (HSCT) TB risk 10 40x higher than general population ~ 10X less common than among SOT (due to transient immunosuppression) Highest risk among allogenic transplants Primarily due to LTBI reactivation Donor derived infections appear insignificant Treatment for LTBI prior to conditioning therapy preferred Recommendations for screening and treatment of LTBI similar to SOT Aguado Microbio Spectrum 2016 Tomblyn Biol Blood Marrow Transplant 2009 TB and Biologics TNF alpha inhibitors Etanercept (soluble p75 receptor) Infliximab, adalimumab, golimumab, certolizumab (monoclonal antibodies) Il 1 inhibitors Anakinra B cell depletion Rituximab Anti CD20 T cell co stimulation Abatacept blockade 23

24 TB and Biologics TNF alpha inhibitors Etanercept (soluble p75 receptor) Infliximab, adalimumab, golimumab, certolizumab (monoclonal antibodies) Il 1 inhibitors Anakinra B cell depletion Rituximab Anti CD20 T cell co stimulation Abatacept blockade TNF alpha and TB Slide courtesy of Elizabeth Gilliams Gardam Lancet Infect Dis

25 TNF alpha and TB X TNF alpha blockade increases TB risk Slide courtesy of Elizabeth Gilliams Gardam Lancet Infect Dis TB risk and TNF alpha inhibitors Dixon Ann Rheum Dis

26 TB risk and TNF alpha inhibitors Slide courtesy of Kevin Winthrop Winthrop Nature Prac Rheum (in press) Winthrop Ann Rheum Disease 2013 TB risk and TNF alpha inhibitors: Risks are different by agent Infliximab and adalimumab suppress IFNγ production Depletion of CD8 cells that aid in killing intracellular TB Impaired granuloma formation Antibodies > receptor Monoclonal Ab Stronger affinity for TNFα Soluble receptor antagonist Slide courtesy of Elizabeth Gilliams Tracey, Pharm & Therapeutics 2018 Saliu JID 2006 Plessner JID

27 LTBI treatment and TNF alpha inhibitors Screen for LTBI prior to anti TNFα initiation Ideally receive 1 month LTBI treatment prior to anti TNFα Holding anti TNFα can be associated with IRISlike phenomenon Anti TNFα can be restarted within few months of TB tx initiation Cantini Autoimmunity Rev 2015 HIV/TB: Take home points HIV significantly increase risk of TB atypical presenta ons of PTB, EPTB and disseminated TB TB treatment similar to non HIV, but Daily Initial phase w/ RIPE, at least 3 x week Maintenance w/ IR Rifamycin based anti TB therapy is key May require ART dose adjustment Important to monitor for drug drug interactions and side effects IRIS typically managed w/ NSAIDS, steroids if severe Concerns for TB IRIS should not delay HAART initiation 27

28 TB and other immunosuppressive states: Take home points Important to screen for LTBI in SOT/HSCT recipients Ideally before transplant TB risk primarily due to LTBI reactivation, but can be donor derived in SOT Rifampicin reduces levels of many immunosuppressant agents used in SOT/HSCT Increases risk of graft rejection Often requires increased dose of immunosuppressants TNF alpha inhibitors significantly increase risk of TB Ideally initiate LTBI treatment before anti TNFα initiation Stopping anti TNFα assoc with IRIS, can restart within few months of TB tx Resources Panel on Opportunistic Infections in HIV Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV infected adults and adolescents: Updated September 22, and adolescent oi prevention andtreatment guidelines/325/tb CDC. Managing Drug Interactions in the Treatment of HIV Related Tuberculosis CDC. Reported Tuberculosis in the United States, Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children opi/diagnosis oftuberculosis in adults and children.pdf WHO. Global Tuberculosis Report Latent TB infection. National HIV curriculum. September occurring conditions/latent tuberculosis/core concept/all Horne DJ, Narita M, Spitters CL, et al. Challenging issues in tuberculosis in solid organ transplantation. Clin Infect Dis Nov;57(10):

29 Acknowledgements Robert Harrington David Horne Masa Narita Bijan Ghassemieh Kevin Winthrop Elizabeth Gilliams Additional references Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med Jul 19;345(3): Geldmacher C, Zumla A, Hoelscher M. Interaction between HIV and Mycobacterium tuberculosis: HIV 1 induced CD4 T cell depletion and the development of active tuberculosis. Curr Opin HIV AIDS May;7(3): Lawn SD, Wood R, Wilkinson RJ. Changing concepts of "latent tuberculosis infection" in patients living with HIV infection. Clin Dev Immunol. 2011;2011 Parimon T, Spitters CE, Muangman N, et al. Unexpected pulmonary involvement in extrapulmonary tuberculosis patients. Chest Sep;134(3): Lawn SD, Meintjes G, McIlleron H, et al. Management of HIV associated tuberculosis in resource limited settings: a state of the art review. BMC Med Dec 2;11:253. ATS (American Thoracic Society) Hepatotoxicity of Antituberculosis Therapy Subcommittee. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med Oct 15;174(8): Meintjes G, Lawn SD, Scano F, et al. Tuberculosis associated immune reconstitution inflammatory syndrome: case definitions for use in resourcelimited settings. Lancet Infect Dis Aug;8(8): Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo controlled trial of prednisone for paradoxical tuberculosis associated immune reconstitution inflammatory syndrome. AIDS Sep 24;24(15): Horne DJ, Narita M, Spitters CL, et al. Challenging issues in tuberculosis in solid organ transplantation. Clin Infect Dis Nov;57(10): Aguado JM, Silva JT, Samanta P, Singh N. Tuberculosis and Transplantation. Microbiol Spectr Nov;4(6). Aguado JM, Torre Cisneros J, Fortún J, et al. Tuberculosis in solid organ transplant recipients: consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology. Clin Infect Dis May 1;48(9): Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant Oct;15(10): Gardam MA, Keystone EC, Menzies R, et al. Anti tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis Mar;3(3): Dixon WG, Hyrich KL, Watson KD, et al. Drug specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis Mar;69(3): Cantini F, Nannini C, Niccoli L, et al. SAFEBIO (Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy). Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice. Autoimmun Rev Jun;14(6): Winthrop KL, Baxter R, Liu L, et al. Mycobacterial diseases and antitumour necrosis factor therapy in USA. Ann Rheum Dis Jan;72(1):

30 HIV/TB 10% new TB cases HIV+ WHO 2016, 2017 Global TB/HIV epidemiology: over time 10.4 million 1.3 million 374, million ~10% new cases HIV+ ~1/4 TB deaths HIV+ WHO

31 Global TB Epidemiology WHO 2017 Global TB/HIV Epidemiology TB and HIV are co epidemics WHO

32 US TB Epidemiology Reported Tuberculosis (TB) Cases United States, * 30,000 No. of Cases 25,000 20,000 15,000 10,000 5, Year CDC 2017 US TB Epidemiology Reported Tuberculosis (TB) Cases United States, * 30,000 No. of Cases 25,000 20,000 15,000 10,000 5,000 0 HIV epidemic contributed to TB resurgence in late 80s Year CDC

33 70 US TB/HIV Epidemiology Estimated HIV Coinfection in Persons with TB, % Coinfection Year All ages Ages yrs CDC US TB/HIV Epidemiology Estimated HIV Coinfection in Persons with TB, % Coinfection Proportion of TB cases with HIV decreasing Year All ages Ages yrs CDC

34 US TB/HIV Epidemiology global = local Estimated HIV/TB Coinfection cases US vs Foreign born, N=3145 # Cases N=500 N=273 N= Year Foreign Born US Born CDC 2017 # Cases US TB/HIV Epidemiology global = local Estimated HIV/TB Coinfection cases US vs Foreign born, N=3145 N= Year HIV+ TB cases among foreign born now exceed US born Foreign Born US Born N=273 N=230 CDC

35 Question A Which of the following is true? A. Globally, TB incidence is increasing B. In the US, TB incidence is increasing C. Globally, incidence of TB among HIV+ is increasing D. In the US, number of new TB cases with HIV who are foreign born exceeds that among US born E. In the US, proportion of new TB cases with HIV is increasing Question B 25 y/o woman from Eritrea, HIV+ not yet on ART with CD4 100 presents with 2 3 month history of enlarging cervical lymph node, fever and weight loss. She denies obvious cough. You are concerned for extrapulmonary TB. Which of the following should be part of the work up for extrapulmonary TB in this HIV+ patient? A. Lymph node biopsy including AFB smear and culture B. CXR C. Sputum AFB smear and culture D. All of the above E. A & B 35

36 Question C 42 y/o HIV+ homeless man is diagnosed with pulmonary TB and started on RIPE. He has a history of significant mental health issues worsened on Atripla (efavirenz + truvada). Because of this (and in line with current US HIV guidelines) you had previously switched his efavirenz to dolutegravir last year. At his next follow up visit, his viral load (previously undetectable) is now >1000. Assuming he has no new HIV resistance, and he has been adherent to both his ART and anti TB therapy, you should A. Decrease his dose of rifampin B. Increase his dose of dolutegravir from 50 mg PO QDAY to BID C. Consider switching rifampin for rifabutin D. B or C 36