Tuberculosis and HIV

Transcription

1 Julian Elliott National Centre in HIV Epidemiology and Clinical Research The University of New South Wales

2 Epidemiology Diagnosis of TB Clinical management

3 Does this woman have tuberculosis?

4 Estimated TB incidence rate, 2004 Estimated new TB cases (all forms) per population or more No estimate The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved WHO Global TB Report 2006

5 Effects of HIV on risk of TB Increased progression from primary or latent TB infection to TB disease HIV negative: 10% lifetime risk HIV positive: 10% annual risk Selwyn NEJM 1989; Braun Am Rev Resp Dis 1991; Daley NEJM 1992; Antonucci JAMA 2005

6 CD Tuberculosis and HIV Natural Course of HIV Infection Infection TB Asymptomatic Months Years Symptomatic TB AIDS PCP MAC Antonucci JAMA 1995; Badri Lancet 2002; Sonnenberg JID 2005

7 Does this woman have tuberculosis? What is her risk of TB? What is the risk that her illness is due to TB?

8 Case series of TB in HIV patients Report Setting Syndrome % Van Cleeff IJTLD 2003 Kenya Cough > 3 weeks 56 Rana JAIDS 2000 Kenya Died in hospital 50 Ansari IJTLD 2002 Botswana Died in hospital 40 Kumarasamy CID 2003 India AIDS defining illness 49 Banda TRSTMH 1998 Malawi Cough < 3 weeks 35 Scott Lancet 2000 Kenya Acute pneumonia 9 Archibald CID 1998 Tanzania Inpatients with fever 23 Mwachari J Infect 1998 Kenya Diarrhoea 13 Adapted from Corbett Lancet 2006

9 ANRS 1260 (Pneumokam) 321 pts 26 excluded 295 pts 88 AFB AFB - 47 indefinite diagnosis 88 PCP 28 TB 48 Broncho Pneumonia 47 Other diagnosis DEFINITE AND PROBABLE DIAGNOSIS RESULTS 39% TB 30% PCP 16% Bacteria 6% Mycosis 5% NTM 4.7% S.stercoralis 0.3% Cancer NB : pathogen association in 15 % cases Mycosis 17 Strongyloidiasis 14 NTM 15 Tumor 1

10 Does this woman have tuberculosis? What is her risk of TB? What is the risk that her illness is due to TB? How can I decide whether she has TB or not?

11 Sputum smear Critical to diagnosis of TB even when HIV + More likely to be negative or scanty WHO recommendations if HIV +/unknown At least two smears A single positive smear = smear positive TB At least two negative smears = smear negative TB Elliott IJTLD 1993; Karstaedt IJTLD 1998; Johnson IJTLD 1998; WHO guidelines for SNTB/EPTB 2006

12 Clinical indicators Classic symptoms Prolonged cough, fever, weight loss Less accurate in HIV especially if CD4 is low More likely to have TB without these symptoms More likely to have these symptoms without TB Jones Am Rev Resp Dis 1993; Samb IJTLD 1997; Siddiqi Lancet Infect Dis 2003

13 Clinical differentiation of TB, PCP and pneumonia Pulmonary tuberculosis Duration Few weeks or longer Fever Moderate to high fever Cough Dry or productive Bacterial Pneumonia Few days to a week High fever Usually productive P. jirovecii pneumonia (PCP) Few weeks or longer Low grade fever Dry SOB Little Little Common Weight Common Not initially No loss LNs Common No No

14 Radiology

15 Radiology

16 Radiology

17 Radiology Classical findings less common Upper lobe involvement Cavities Atypical findings more common Lower lobe involvement Diffuse infiltrates Lymphadenopathy Minor changes Normal Training, supplies, maintenance and support Harries IJTLD 1998; van Cleef BMC Infect Dis 2005; Abouya IJTLD 1995; Aderaye Infection 2004

18 Trial of antibiotics Some evidence that a trial of antibiotics can help differentiate TB from bacterial infections BUT TB and bacterial infections may both be present (especially in people with HIV) TB symptoms can fluctuate Bacterial infections can be resistant Can lead to more bacterial drug resistance and delayed treatment of TB WHO: use for treatment not diagnosis Wilkinson TRSTMH 1997; Siddiqi Lancet Infect Dis 2003; WHO guidelines for SNTB/EPTB 2006

19 WHO algorithm for diagnosis of TB in ambulatory HIV patients WHO guidelines for SNTB/EPTB 2006

20 WHO algorithm for diagnosis of TB in seriously ill HIV patients WHO guidelines for SNTB/EPTB 2006

21 What treatment should she receive?

22 Anti-tuberculosis therapy 6 month course (2HRZE/4HR) Better than 8 month (2HRZE/6HE) Daily doses during intensive phase Better than intermittent Directly observed therapy Conflicting randomised trial data Emphasis is now on patient centered approach which may include direct observation Jindani Lancet 2004; Okwera IJTLD 2006; Volmink Cochrane Rev 2003; International Standards for TB care 2006

23 Cotrimoxazole Report Design Setting Mortality reduction Wiktor Lancet 1999 RCT Cote d Ivoire 48% Badri Lancet 1999 RCT South Africa 53% Zachariah AIDS 2003 Observational Malawi 19% Grimwade AIDS 2005 Observational South Africa 29% Nunn unpublished RCT Zambia 16% Mermin Lancet 2004 RCT (all PLHA) Uganda 46% Chintu Lancet 2004 RCT (children) Zambia 43% Mermin AIDS 2005 RCT (family) Uganda 63% <10yrs

24 Antiretroviral therapy Who? Cambodia: start ART if CD4 < 250 WHO 2006: start if WHO 4 or CD4 < 350 When? Not too late: high mortality Not too early: IRIS, drug toxicity, drug interactions, pill burden Await results of CAMELIA In the meantime CD4 < 200: start between 2 and 8 weeks as soon as TB treatment tolerated CD : start after 8 weeks CD4 > 250: defer ART WHO ARV guidelines adults/adolescents 2006

25 Antiretroviral therapy Which drugs? Efavirenz <60kg and rifampicin: no dose adjustment >60kg and rifampicin: limited data Nevirapine Studies from Europe and Thailand show good short term virological outcomes Recent report from Africa of sub-therapeutic levels during lead in phase Concern regarding hepatotoxicity Patel JAIDS 2004; Pedral-Sampaio BJID 2004; Manosuthi IAC 2004; Sheehan IWCPHT 2005; Almond IWCPHT 2005; Autur IAC 2004; Oliva AIDS 2003; Ribera JAIDS 2001; Dean AIDS 1999; Van Cutsem IAS 2005; van Oosterhout IAC 2006

26 Antiretroviral therapy Triple nucleosides (AZT + 3TC + ABC or TDF) No dose adjustment needed Can be taken by pregnant women and women with high CD4 counts Randomised trial evidence of lower efficacy Little data regarding use during TB treatment Protease inhibitors Need to use ritonavir boosting and dose adjust Hepatotoxicity Rifabutin Can be combined with NVP or dose adjusted PI Justesen CID 2004; la Porte AAC 2004; Losso Antivir Ther 2004

27 Immune restoration disease (IRD) Restoration of immune function precipitates response to pre-exisiting pathogens Paradoxical reaction variant = deterioration in preexisting clinical illness Unmasking variant = onset of clinical illness after initiation/change of ART Commonly fever, respiratory, lymph node Usually in first 3 months of ART start/change More common if low CD4 Difficult to differentiate from other causes Corticosteriods can be used for serious cases Narita AJRCCM 1998; Breen Thorax 2004;; Lawn Lancet Infect Dis 2005; French AIDS 2004

28 Van den Broek IJTLD 1998; El-Sadr CID 2001; Quy IJTLD 2006; Burman AJRCCM 2001; Murray AJRCCM 1999; Sonnenberg Lancet 2001 Tuberculosis and HIV Outcomes of anti-tuberculosis therapy Same response as HIV negative TB patients Increased risk of side-effects and interactions Increased mortality Due to TB during first month Due to other causes after first month Increased risk of TB recurrence In high TB transmission settings this is mostly due to reinfection Higher rates of TB drug resistance in some studies

29 Antiretroviral therapy Co-management Nosocomial transmission

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