HIV and TB Co-contamination North Dakota HIV Symposium May 19, 2010

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HIV and TB Co-contamination North Dakota HIV Symposium May 19, 2010. David McNamara, M.D. Clinical Right hand Educator of Pharmaceutical College of North Dakota Irresistible Malady Division MeritCare, Fargo ND . Divulgences . No business revelations Dakota Helps Instruction and Preparing Center .

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HIV and TB Co-disease North Dakota HIV Symposium May 19, 2010 David McNamara, M.D. Clinical Assistant Professor of Medicine University of North Dakota Infectious Disease Division MeritCare, Fargo ND

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Disclosures No business exposures Dakota AIDS Education & Training Center

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Learning Objectives Learners ought to be acquainted with: Epidemiology of HIV-TB Co-contamination HIV screening in TB contamination Drug collaborations between pharmaceuticals for HIV and TB

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Overview Scope of Problem TB in HIV contamination Diagnosis Treatment Drug Interactions Summary

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Catastrophic impact of TB and HIV contamination Worldwide 2008: 33.2 million people HIV+ ~ 30% co-tainted with TB 9.4 million new TB cases 40% expansion from 1990 Driven by HIV plague Convergence of Two Epidemics Chaisson R. JID 2010:201 (1 March)

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Epidemiology ~ 1/3 HIV tainted people worldwide are contaminated with TB (typically dormant) 8-10% create dynamic malady every year 2007 9.27 million new TB cases 15% happened in HIV+ people Africa 80% India 11% 450,000 passings from TB in HIV+ people Swaminathan S. CID 2010:50 (15 May)

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Mortality Worldwide 1.8 million passings from TB in 2007 25% (450,000) likewise HIV+ 2 million passings from HIV 22% from TB the main source of death in HIV contamination adds to ~ 1/4 TB passings

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Geographic Distribution WHO Global Tuberculosis Control 2009 Report

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Swaminathan S. CID 2010:50 (15 May)

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Estimated HIV Coinfection in Persons Reported with TB, United States, 1993–2008* % Coinfection *Updated as of May 20, 2009. Note: Minimum appraisals in view of revealed HIV-positive status among all TB cases in the age bunch.

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Implications Global TB frequency and mortality would diminish notwithstanding HIV plague Increasingly, need to oversee patients with both HIV and TB Why this destructive cooperative energy between these two contaminations? Swaminathan S. CID 2010:50 (15 May)

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Overview Scope of Problem TB in HIV contamination Diagnosis Treatment Drug Interactions Summary

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Biology of TB If airborne TB breathed, face to face gets to be distinctly tainted Most create dormant (latent) TB Infection resistant framework sequesters TB bacilli and anticipates dynamic disease can reactivate to dynamic TB in future ~5-10% lifetime chance for HIV contrary ~ 8-10% every year with untreated HIV Some create dynamic TB immediately Will feel wiped out, spread sickness to others More likely if immunocompromised HIV, chemotherapy, elderly, malnourished

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Biology of HIV disease drains CD4+ T cells T-cell arm of safe framework Cellular control of disease with Viruses Fungi Mycobacteria HIV-tainted patients defenseless against disease with pathogens that safe framework generally controls

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HIV Infection: CD4 Cell Decline

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Manifestations of TB in HIV+ people Depends on level of immunosuppression Early HIV contamination like non-HIV patients pneumonic malady prevails AIDS: extreme immunosuppression extrapulmonary destinations regular miliary, lymphadenitis paucibacillary ailment, lymphadenitis Similar to youth TB AFB-spread pessimistic aspiratory illness

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HIV-TB Challenges Prompt finding Effective treatment Successful aversion procedures TB Recurrence in HIV+ people after treatment fruition

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Recurrence of TB HIV-adverse patients with 4-tranquilize treatment and DOT 2-3% repeat HIV-constructive patients 14+ % repeat rate Some backslide with unique strain Most re-contaminate with new strain Often with MDR TB Why this inconsistency? TB treatment does not adjust continuous immunosuppression chance for TB presentation

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What can lessen repeat rates? Finish DOT for all patients with TB ART for patients with TB and HIV Infection control in HIV and TB mind settings

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Overview Scope of Problem TB in HIV contamination Diagnosis Treatment Drug Interactions Summary

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Challenges in Diagnosis of HIV-related TB Fewer bacilli in sputum than HIV – Sputum AFB spread standard demonstrative technique in many areas HIV+ patients more prone to have spread negative aspiratory TB Sputum AFB culture moderate, not promptly accessible CXR: less delicate in HIV+ ~ 14-22% HIV + patients with pneumonic TB have ordinary CXR

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Diagnostic Methods Microscopy AFB spread Cheap, fast Depends on bacterial load Low affectability in HIV ~ 45% Culture More touchy than microscopy Can utilize tests on +culture to separate TB from NTM (basic in HIV+ patients)

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Diagnostic Methods Sputum coordinate Probe (MTD) Sensitivity variable in spread negative ailment Expensive, complex to perform PPD skin test Poor affectability in HIV because of anergy Can't separate inactive versus dynamic sickness Poor affectability in setting of dynamic TB In HIV negative patients, just ~ half +PPD QuantiFERON blood test Interferon gamma discharge examine Can't separate dormant versus dynamic TB Does not separate amongst IRIS and disappointment of TB treatment

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Diagnosis of HIV All patients with dynamic TB require a HIV blood test Order: HIV 1/2 Antibody HIV/TB co-disease essentially impacts forecast and medication treatment Treat both HIV and TB Protease Inhibitor Antiretrovirals huge cooperation with Rifampin

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Reporting of HIV Test Results in Persons with TB by Age Group United States, 1993–2008* % with Test Results *Updated as of May 20, 2009. Note: Includes TB patients with positive, negative, or uncertain HIV test comes about. People from California detailed with AIDS just through 2004. (HIV test results are not detailed from California)

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WHO Global Tuberculosis Control 2009 Report

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Overview Scope of Problem TB in HIV contamination Diagnosis Treatment Latent TB in setting of HIV Active TB with HIV co-disease When to begin ART (AntiRetroviral Therapy) Drug Interactions Summary

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Latent TB and HIV contamination Screen for inactive TB in HIV+ patients PPD skin test ( > 5 mm positive) QuantiFERON blood test can be utilized; restricted information Isoniazid 300mg PO day by day x 9 months

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Treatment of Active TB with HIV Co-disease Refer to doctor master in both HIV and TB treatment Public Health RN for DOT Why? Chance for disappointment high negative results to patient, close contacts and group

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Treatment of Active TB with HIV Co-contamination Basic standards in HIV+ like non HIV-TB particular difficulties Frequency of hostile to mycobacterial organization Drug communications Overlapping drug toxicities IRIS: Immune Reconstitution Inflammatory Syndrome

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First-line TB treatment Induction stage: two months INH, RIF, PZA, EMB day by day or 3x/week Continuation stage: 18 weeks INH, RIF day by day or 3x/week Every exertion ought to be made to utilize rifamycin-based treatment for whole course Continuation stage: maintain a strategic distance from once-week by week INH-rifapentine 2x/week dosing

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Treatment: DOT Directly Observed Therapy Mandatory for all dynamic tuberculosis Critical for HIV-TB Co-disease Risk of backslide is higher Public Health RN

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Treatment: When to begin antiretroviral treatment? Ideal planning of start of ART in dynamic TB has been dubious Concerns Drug cooperations (rifampin and PIs) Overlapping drug toxicities IRIS High pill trouble Programmatic challenges

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Karim et al. NEJM 362;8. Feb. 25, 2010 SAPIT Trial, South Africa 642 patients with TB, HIV and CD4 <500 cells/uL Randomized to 3 bunches for ART start Early Integrated: inside 4 weeks Late Integrated: inside 4 weeks of finish of Intensive stage TB treatment Sequential: After fruition of TB treatment

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Study ceased ahead of schedule because of diminished mortality in incorporated treatment bunches 56% relative decrease in danger of death Adverse impacts comparative between gatherings Karim et al. NEJM 362;8. Feb. 25, 2010

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IRIS: Immune Reconstitution Inflammatory Syndrome Worsening of side effects or X Ray with immunologic recuperation Occurs with contaminations in settings of immunosuppression when invulnerable framework recoups HIV, chemotherapy, immunosuppressants Mycobacterial and contagious sicknesses Common as CD4 cell number enhances with ART Hard to differentiate between treatment disappointment and IRIS Treat with steroids Occasionally may need to hold ART

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Overview Scope of Problem TB in HIV disease Diagnosis Treatment Drug Interactions Summary

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Drug Interactions Significant medication cooperations between foundation drugs antimycobacterials rifampin, rifabutin antiretrovirals Protease Inhibitors NNRTIs: efavirenz Despite this, basic to treat TB with rifamycin-based treatment if at all conceivable

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Sterling TR CID 2010; 50(S3):S223-230

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Drug Interactions Rifamycins and Protease Inhibitors Rifampin will  PI levels Avoid rifampin and PIs Use efavirenz-based ART if conceivable low measurements Rifabutin alright with PIs Rifabutin 150 mg 3x/week Rifampin and NNRTI utilize high dosage efavirenz 800 mg every day Avoid rifampin and raltegravir

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Drug Interactions Treatment of TB-HIV co-contamination by doctor master in treatment of both Verify regimens and dosing with references Incorrect dosing prompts to: Resistance in both HIV and TB Treatment disappointment Spread of medication safe TB

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Overview Scope of Problem TB in HIV disease Diagnosis Treatment Drug Interactions Summary

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Summary Screen for HIV Maintain high file of doubt for TB in HIV Patients with HIV-TB co-contamination ought to be overseen by doctor master in both illnesses All patients with dynamic TB require a HIV test All patients with TB require DOT

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Acknowledgments Anne