tb/hiv and other immunosuppressive states · 2019-12-18 · tb/hiv and other immunosuppressive...

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TB/HIV and other immunosuppressive states

Sylvia LaCourse MD, MPHDepartment of Medicine, Division of Allergy & Infectious Disease

TB Clinical IntensiveSeattle, 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)

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Latent TB (LTBI) and active TB

Small, NEJM 2001


Small, NEJM 2001

HIV‐ 10% over lifetimegreatest risk in 1st 2 years

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Small, NEJM 2001

HIV‐ 10% over lifetimegreatest risk in 1st 2 years

HIV+ 10% per year

• 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, 2012

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Lawn Clin Dev Immunology 2011

MTb infec on → TB disease

Lawn, Clin Dev Immunology 2011

MTb infec on → TB disease

Although ART significantly decreases TB risk, still much higher than among

HIV‐

ART (+ TPT)

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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

DHHS 2017

Important to evaluate for PTB in HIV+ with EPTB

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 extra‐pulmonary

E. A & B

F. C & D

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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 2016DHHS 2017

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

INH/RIF 4 months Twice weekly Not recommended for HIV+

INH/RPT 4 months Once weekly Contraindicated

TB treatment in HIV+

ATS, CDC, IDSA CID 2016DHHS 2017

For HIV+ both initial phase and continuous phase are given daily

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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 2017CDC 2013ATS, 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 2017ATS, CDC, IDSA CID 2016

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ARV ARV dose change RIF dose change Comments

NNRTIs

Efavirenz None;some ↑800mg if >50kg

No change Preferred Regimen (still!)

Nevirapine ↑lead‐in dose 200 mg twice daily, continue as maintenance dose

No change Avoid lead‐in 200mg once daily, assoc w/ virologicfailureConsider therapeutic drug monitoring.Rarely used in US

RilpivirineEtravirine

Contraindicated Significant decrease in Rilpivirine

NRTIs

Tenofovir disoproxil fumarate (TDF)

None None Preferred

Tenofovir alafenamide (TAF)

Unknown TAF concentration decreased in healthy volunteers (but intracellular concentrations still higher than TDF) CROI 2018

ART and RIF recommended dose adjustments

DHHS 2017CDC 2013ATS, CDC, IDSA CID 2016CROI 2018

RIF decreases NNRTI (and some NRTI) levels

ARV dose change RIF dose change Comments

Integrase inhibitors

Raltegravir ↑ Raltegravir to 800 mg twice daily

No change Raltegravir trough concentrations still decreased, follow VL carefully

Dolutegravir ↑ Dolutegravir to 50 mg twice daily

No change follow VL carefully

Bictegravir Bictegravir should not be used together Decrease in Bictegravir even when given BID(Custodia, CROI 2018)

Elvitegravir, cobicistat, TDF or TAF, and emtricitabine (Stribild or Genvoya)

Stribild or Genvoya and rifampin should not be used together

Marked decrease in elvitegravir and cobicistatconcentrations predicted based on metabolic pathways of these drugs

CCR‐5 receptor antagonists

Maraviroc ↑ Maraviroc to 600 mg twice‐daily

No change Use with caution, as there is no reported clinical experience with increased dose of maraviroc with rifampin

ART and RIF recommended dose adjustments (cont.)


RIF decreases INSTI levels

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ARV dose change RIF dose change Comments

ART and RIF recommended dose adjustments (cont.)

Protease inhibitors

Lopinavir/ritonavir(Kaletra™)

Lopinavir 800 mg plus ritonavir 200 mg twice daily (double dose)

No change Hepatotoxicity in healthy volunteers Better‐tolerated among HIV+ already on LPV/r

“Super‐boosted” lopinavir/ritonavir(Kaletra™)

Lopinavir 400 mg plus ritonavir 400 mg twice daily (super boosting)

No change Hepatotoxicity in healthy volunteers

Atazanavir (single agent or ritonavir boosted)Darunavir/rFosamprenavir/rSaquinavir/r

Contraindicated Significant decrease in PIs, Increased PI doses associated +/‐ hepatotoxicity


For PIs RFB preferred

ARV ARV dose change RFB dose change Comments

NNRTIs

Efavirenz No change ↑ 600 mg (daily or thrice‐weekly)

RIF preferred

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)

No change ↓150 mg daily No pub clinical experienceMonitor closely for potential rifabutin toxicity – uveitis, hepatotoxicity, and neutropenia

Darunavir/rFosamprenavir/rSaquinavir/r

No change ↓150 mg daily Monitor closely for potential rifabutin toxicity – uveitis, hepatotoxicity, and neutropenia

Lopinavir/ritonavir(Kaletra™)

No change ↓150 mg daily Hepatotoxicity in healthy volunteers Better‐tolerated among HIV+ already on LPV/r

ART and RFB recommended dose adjustments


RFB levels decreased with EFV, increased with PIs

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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™)

Stribild (or Genvoya) and rifabutin should not be used together

Marked ↓elvitegravir, cobicistat concMarked ↑rifabutin

CCR‐5 receptor antagonists

Maraviroc No change No change No clinical experience; a significant interaction is

unlikely, but this has not yet been studied

ART and RFB recommended dose adjustments (cont.)


INSTI levels increased with RFB

ART and TB treatment: Overlapping toxicities

Lawn, BMC Medicine, 2013

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 EFV Cycloserine, ethionamide, quinolones, INH

Rash NVP, EFV, ABC R,I,P,E, streptomycin, quinolones, PSA, clofzamine

Cytopenia AZT, 3TC R,I, linezolid, rifabutin

Cardiac conduction PIs Bedaquiline, quinolone, clofazamine

Pancreatitis D4T, ddI Linezolid

Lactic acidosis D4T, ddI Linezolid

Upon re‐challenge >90% patients tolerate medications without a recurrence of the adverse effect

ATS, Am J Respir Crit Care Med, 2006

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Question 2Which 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, 2008

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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 AIDS, 2010

TB IRIS: Treatment

• Continue ART unless life‐threatening

• Steroids– RCT 4 wks prednisone vs. placebo for TB IRIS

– ↓ symptoms, improvedCXR, ↓ hospitaliza on

• NSAIDS

Recent trials: • Empiric prednisone during 1st 4

wks of ART ↓ risk of paradoxical TB‐IRIS by 30% Meintjes CROI 2017

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Question 3a23 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 3bShe 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

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TB and HIV

LTBI and HIV

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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 interactionsMay required dose adjustment

Rifabutin 4 months Drug interactionsMay required dose adjustment

Rifampin + Pyrazinamide

2 months Contraindicated

LTBI treatment in HIV+

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 445 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)

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Shifting gears

https://www.bicycling.com/training/a20004265/how‐to‐shift/

Horne CID 2013, Aguado CID 2009

TB and Solid Organ Transplant (SOT)

• TB risk 20‐74 x higher than general pop• Incidence in low prevalence regions 0.3‐6.5%

• Higher mortality 6‐22% (vs <5% for TB in general US)

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Horne CID 2013 Aguado CID 2009

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

Aguado CID 2009

TB and SOT: risk factors

• Transplant‐related immunosuppression

• Standard TB risk factors

• Underlying medical condition

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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

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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

LTBI and SOT: treatment

• Timing: pre‐ or post‐transplant?

Horne CID 2013

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LTBI and SOT: treatment• Choice of regimen


INHBest studiedwell tolerated pre‐liver txp

Longer duration↑ Hepatotoxicity post‐txp

RIF Shorter duration

↑ P450 inducer↓ immunosuppressive agents; rejection allograft loss

INH/RPT Shorter durationDoesn’t avoid INH adverse effects / rifamycin drug interactions

• Need for further study: RBT, FLQ

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 2009

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Question 549 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

C. RIPE therapy should be initiated with reduced RIF dose to avoid drug‐drug 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

Horne CID 2013, Winthrop Am J Transplant 2004

Aguado Microbio Spectrum 2016

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

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Aguado Microbio Spectrum 2016Tomblyn Biol Blood Marrow Transplant 2009

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

TB and Biologics

TNF alpha inhibitors Etanercept (soluble p75 receptor)Infliximab, adalimumab, golimumab, certolizumab (monoclonal antibodies)

Il‐1 inhibitors Anakinra

B‐cell depletion RituximabAnti‐CD20

T‐cell co‐stimulation blockade

Abatacept

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TB and Biologics

TNF alpha inhibitors Etanercept (soluble p75 receptor)Infliximab, adalimumab, golimumab, certolizumab (monoclonal antibodies)

Il‐1 inhibitors Anakinra

B‐cell depletion RituximabAnti‐CD20

T‐cell co‐stimulation blockade

Abatacept

TNF alpha and TB

Gardam Lancet Infect Dis. 2003Slide courtesy of Elizabeth Gilliams

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TNF alpha and TB

Gardam Lancet Infect Dis. 2003

X

TNF alpha blockade increases TB riskSlide courtesy of Elizabeth Gilliams

TB risk and TNF alpha inhibitors

Dixon Ann Rheum Dis 2010

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TB risk and TNF alpha inhibitors

Winthrop Nature Prac Rheum (in press)Winthrop Ann Rheum Disease 2013

Slide courtesy of Kevin Winthrop

TB risk and TNF alpha inhibitors:Risks are different by agent

Tracey, Pharm & Therapeutics 2018Saliu JID 2006Plessner JID 2007

Slide courtesy of Elizabeth Gilliams

Monoclonal AbStronger affinity for TNFα

Soluble receptor antagonist

• Infliximab and adalimumab suppress IFNγ production

• Depletion of CD8 cells that aid in killing intracellular TB

• Impaired granuloma formation

– Antibodies > receptor

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Cantini Autoimmunity Rev 2015

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 IRIS‐like phenomenon– Anti‐TNFα can be restarted within few months of TB tx initiation

• 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

HIV/TB: Take home points

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• 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

TB and other immunosuppressive states: Take home points

ResourcesPanel 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, 2017. https://aidsinfo.nih.gov/guidelines/html/4/adult‐and‐adolescent‐oi‐prevention‐and‐treatment‐guidelines/325/tb

CDC. Managing Drug Interactions in the Treatment of HIV‐Related Tuberculosis. 2013. http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm

CDC. Reported Tuberculosis in the United States, 2016. 2017. https://www.cdc.gov/tb/statistics/reports/2016/default.htm

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. 2017. https://www.thoracic.org/statements/resources/tb‐opi/diagnosis‐of‐tuberculosis‐in‐adults‐and‐children.PDF

WHO. Global Tuberculosis Report 2017. http://www.who.int/tb/publications/global_report/en/

Latent TB infection. National HIV curriculum. September 2017

https://www.hiv.uw.edu/go/co‐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. 2013 Nov;57(10):1473‐82.

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AcknowledgementsRobert Harrington

David Horne

Masa Narita

Bijan Ghassemieh

Kevin Winthrop

Elizabeth Gilliams

Additional referencesSmall PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med. 2001 Jul 19;345(3):189‐200.

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. 2012 May;7(3):268‐75.

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. 2008 Sep;134(3):589‐594.

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. 2013 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. 2006 Oct 15;174(8):935‐52.

Meintjes G, Lawn SD, Scano F, et al. Tuberculosis‐associated immune reconstitution inflammatory syndrome: case definitions for use in resource‐limited settings. Lancet Infect Dis. 2008 Aug;8(8):516‐23.

Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo‐controlled trial of prednisone for paradoxical tuberculosis‐associated immune reconstitution inflammatory syndrome. AIDS. 2010 Sep 24;24(15):2381‐90.

Horne DJ, Narita M, Spitters CL, et al. Challenging issues in tuberculosis in solid organ transplantation. Clin Infect Dis. 2013 Nov;57(10):1473‐82.

Aguado JM, Silva JT, Samanta P, Singh N. Tuberculosis and Transplantation. Microbiol Spectr. 2016 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. 2009 May 1;48(9):1276‐84.

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. 2009 Oct;15(10):1143‐238.

GardamMA, Keystone EC, Menzies R, et al. Anti‐tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis. 2003 Mar;3(3):148‐55.

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. 2010 Mar;69(3):522‐8.

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. 2015 Jun;14(6):503‐9.

Winthrop KL, Baxter R, Liu L, et al. Mycobacterial diseases and antitumour necrosis factor therapy in USA. Ann Rheum Dis. 2013 Jan;72(1):37‐42.

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HIV/TB

WHO 2016, 2017

10% new TB cases HIV+

Global TB/HIV epidemiology: over time

WHO 2017

~10% new cases HIV+ ~1/4 TB deaths HIV+

1.3 million

374,000

10.4 million

1.2 million

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Global TB Epidemiology

WHO 2017

Global TB/HIV Epidemiology

WHO 2017

TB and HIV are co‐epidemics

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0

5,000

10,000

15,000

20,000

25,000

30,000

1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

Reported Tuberculosis (TB) Cases United States, 1982–2016*

No. o

f Cases

Year

US TB Epidemiology

CDC 2017

0

5,000

10,000

15,000

20,000

25,000

30,000

1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

Reported Tuberculosis (TB) Cases United States, 1982–2016*

No. o

f Cases

Year

US TB Epidemiology

CDC 2017

HIV epidemic contributed to TB resurgence in late 80s

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US TB/HIV EpidemiologyEstimated HIV Coinfection in Persons with TB,

1993 – 2016% Coinfection

CDC 2017

0

10

20

30

40

50

60

70

1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

All ages Ages 25–44 yrsYear

US TB/HIV EpidemiologyEstimated HIV Coinfection in Persons with TB,

1993 – 2016

% Coinfection

CDC 2017

0

10

20

30

40

50

60

70

1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

All ages Ages 25–44 yrsYear

Proportion of TB cases with HIV decreasing

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US TB/HIV Epidemiologyglobal = local

Estimated HIV/TB Coinfection cases US vs Foreign born, 1993 – 2016

# Cases

CDC 2017

0

500

1000

1500

2000

2500

3000

3500

1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014

Foreign Born US BornYear

N=3145

N=500

N=273

N=230

US TB/HIV Epidemiologyglobal = local

Estimated HIV/TB Coinfection cases US vs Foreign born, 1993 – 2016

# Cases

CDC 2017

0

500

1000

1500

2000

2500

3000

3500

1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014

Foreign Born US BornYear

N=3145

N=500

N=273

N=230

HIV+ TB cases among foreign born now exceed US born

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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 B25 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

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Question C42 y/o HIV+ homeless man is diagnosed with pulmonary TB andstarted on RIPE. He has a history of significant mental healthissues worsened on Atripla (efavirenz + truvada). Because of this(and in line with current US HIV‐guidelines) you had previouslyswitched his efavirenz to dolutegravir last year. At his nextfollow‐up visit, his viral load (previously undetectable) is now>1000.

Assuming he has no new HIV resistance, and he has beenadherent 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

tb/hiv and other immunosuppressive states · 2019-12-18 · tb/hiv and other immunosuppressive...

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