1. TB and HIV co-infection BHIVA Clinical Audit Sub-Committee: M Backx, C Ball, G Brook, P Bunting, C Carne, A DeRuiter, K Foster, A Freedman, P Gupta, V Harindra, M Johnson, G McCourt, C O’Mahony, E Monteiro, E Ong, K Orton, R Pebody, A Rodger, C Sabin, R Weston, E Wilkins, D Wilson, M Yeomans

2. Aim of audit To assess adherence to guidelines for management of TB/HIV co-infected patients including:  BHIVA treatment guidelines for TB/HIV infection, 2005. (BHIVA)  National Collaborating Centre for Chronic Conditions: Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control, 2006. (NCCCC)  Stopping tuberculosis in England: an action plan from the Chief Medical Officer, 2004. (CMO)  HPA Standards Unit. BSOP 40 Investigation of samples for mycobacterium species, 2006. (HPA).

3. Methods and participation Casenote review of 236 HIV positive adults who started treatment for active TB during October 2007 – April 2008:  Data were collected October-December 2008 so most cases had time to complete treatment.  Chemoprophylaxis for latent TB was excluded.  Suspected/unconfirmed cases were included unless TB therapy was stopped on medical grounds due to confirmed alternative diagnosis. Accompanying surveys completed by 124 HIV treatment sites and 18 TB clinics/units.

4. Arrangements for care of HIV/TB co-infected patients  19 (15.3%) HIV sites were integrated departments managing both HIV and TB mono- and co-infected patients.  69 (56%) HIV sites, 16 (89%) TB sites: HIV and TB clinicians liaise, each managing respective aspects of care.  12 (10%) HIV sites, 3 (17%) TB sites: hold joint clinics for co-infected patients.  12 (10%) HIV sites, 0 TB sites: HIV clinicians manage uncomplicated TB, refer more complex cases. NB percentages do not add up because respondents could select more than one option.

5. Responsibility for notification of TB in HIV patients Base is all responding sites, whether HIV, TB or integrated services.

6. Communication of HIV status Of those who notify TB cases outside their main or host commissioning area:  68 (71%) routinely include information that a patient is also HIV positive, unless the patient refuses consent  12 (12%) sometimes do so  16 (17%) do not. Of the 19 integrated and 18 TB services, 3 (8%) use different tests when screening close household contacts of an HIV positive as compared with HIV negative TB index case.

7. Policies on HIV testing of TB patients Guidelines: All patients with TB should have risk assessments for HIV (NCCCC). All patients with TB should be offered an HIV test, regardless of risk (BHIVA). 2008 national HIV testing guidelines: Testing should be routinely offered and recommended. NB: TB and integrated services gave their own policy. Other HIV services answered according to what they believed their local TB service’s policy to be.

8. Policies on latent TB screening for HIV patients Consistent with guidelines, 95 (77%) of HIV/integrated services do not routinely screen newly diagnosed HIV patients for latent TB.  14 (11%) screen those from high TB prevalence countries  6 (5%) screen other selective groups  6 (5%) screen all  3 (2%) did not answer.

9. Rapid resistance testing The 47 sites which treat TB* were asked about rapid molecular testing for rifampicin resistance. Of the 37 which responded:  17 (46%) did rapid testing routinely for HIV patients  18 (49%) took HIV status into account when considering rapid testing  2 (5%) did not use rapid testing. *ie 18 TB services, 19 integrated services, and 10 HIV services which manage uncomplicated TB cases themselves. Guidelines: If a risk assessment suggests MDR TB, rapid testing should be done for rifampicin resistance. HIV patients are at increased risk (NCCCC, BHIVA).

10. TB key-workers All sites were asked who would normally act as key worker for an HIV/TB patient:  89 (63%): TB nurse specialist  11 (8%): HIV nurse specialist  9 (6%): HIV/TB nurse specialist  11 (8%): other clinician(s)  22 (15%): unsure or no answer. Guidelines: All people with TB should have a key worker to help educate and promote treatment adherence (NCCCC). Best practice includes named case manager assigned to every TB patient (CMO).

11. Patient data from casenote review

12. Demographic data Patients (N=236) were:  52.5% female, 47.0% male, 0.4% not stated  74.6% black-African, 9.7% white, 6.8% Asian, 3.8% black-other, 3.0% other, 2.1% not known/not stated  13.6% under 30, 73.7% 30-50, 9.8% over 50, 3.0% not stated  84.7% born in high TB prevalence country (overwhelmingly in Africa), 4.7% in non-UK low TB prevalence country, 9.3% in UK, 1.3% not known/not stated.

13. TB notification Had TB been notified?  85 (36.0%) recorded in notes  113 (47.9%) believed to have been done  6 (2.5%) not done  28 (11.9%) not known  4 (1.7%) no answer. Among 132 patients for whom information was given, HIV status had been passed on with the TB notification for 87 (65.9%) and had not for 45 (34.1%). NB: “Not known” on this and subsequent slides may reflect audit completion on basis of HIV notes without access to TB clinic notes. Guidelines: Notification is required by law. The doctor making or suspecting the diagnosis is legally responsible.

14. TB key worker Was the identity of the patient’s TB key worker recorded in HIV notes?  150 (63.6%) yes, name and contact details documented  59 (25.0%) believed to have a key worker but details not documented  10 (4.2%) no key worker*  17 (7.2%) not known/not answered. *including one long-stay inpatient. Guidelines: All people with TB (except inpatients) should have a key worker to help educate and promote treatment adherence (NCCCC). Best practice includes named case manager assigned to every TB patient (CMO).

15. TB contact tracing Had TB contact tracing been done?  152 (64.4%) yes  20 (8.5%) no  64 (27.1%) not known/not answered. Guidelines: Once a person has been diagnosed with active TB, the need for contact tracing should be assessed without delay. Screening should be offered to the household contacts of any person with active TB (NCCCC)..

16. HIV clinic attendance since TB diagnosis *1 death was attributed to TB, 1 to drug hepatotoxicity, 1 other cause, 3 unknown. Number of patients Percent of patients Attends regularly18578.4 Attends, some missed appointments218.9 Stopped: died*62.5 Stopped: left UK93.8 Stopped: transferred care within UK52.1 Stopped: not known to have died, left UK or transferred 93.8 Not answered10.4 Total236100.0

17. Timing of HIV diagnosis  131 (55.5%) before seeking care for TB  80 (33.9%) during investigation of TB  19 (8.1%) via routine screening as a result of TB diagnosis  4 (1.7%) after TB diagnosis but not via routine screening  2 (0.9%) unclear/not known/not answered. Of the 4 HIV diagnoses not made before or as a result of the TB, 2 had declined screening and 1 had not been offered it (TB diagnosis was not confirmed). Information was missing for the other.

18. HIV disease stage at TB diagnosis CD4 count in cells/mm 3 nearest in time to diagnosis of active TB was:  163 (69.1%) under 200, including 73 whose HIV had been diagnosed before seeking care for TB  36 (15.3%) 201-350  20 (8.5%) 351-500  13 (5.5%) over 500  4 (1.7%) not known/not answered.

19. Site of TB Totals do not add because there could be more than one site. Number of patientsPercent of patients Pulmonary13758.1 Any extrapulmonary, comprising:14059.3 Peripheral lymph node6125.8 Meningeal208.5 Disseminated, including miliary4418.6 Other3514.8

20. TB diagnosis Method or basis of diagnosis Number of patients Percent of patients Culture (any site)13657.6 AFB microscopy (any site), without culture3213.6 NAAT, without culture or AFB10.4 Cytology/histology without culture, AFB or NAAT125.1 None of the above reported5523.3

21. Culture confirmation of pulmonary cases Of 137 patients with pulmonary TB:  60 (43.8%) were sputum smear positive  69 (50.4%) had a positive sputum culture  A further 21 (15.3%) had a positive culture other than sputum.  This gives a total of 65.7% culture-confirmed cases. Guidelines: At least 65% of pulmonary cases to be culture-confirmed (CMO).

22. Time to receive sputum smear results Guidelines: Positive results within 24 hours, 6 day/week service. Written reports in 16-72 hours (HPA). Interval between taking sample and receiving result for patients with positive sputum smear Number of patients Percent of patients Same day1220.0 Next day1525.0 2 days813.3 3 days23.3 4+ days1525.0 Not answered813.3 Total60100.0

23. TB drug resistance  11 patients had known TB drug resistance at the time of initial prescribing (8 isoniazid, 2 streptomycin, 1 ethambutol).  3 were later found to have drug resistance (1 MDR, 2 isoniazid).  2 showed evolving resistance to drugs to which they were initially susceptible (1 initially streptomycin resistant became partially rifamycin resistant, 1 initially fully susceptible became isoniazid/streptomycin resistant).

24. Assessment of likely adherence 158 (66.9%) of patients were assessed for likely adherence before starting TB treatment:  139 were expected to adhere well (5 received DOT)  18 were expected to adhere poorly (13 received DOT)  For 1 the outcome of the assessment was not known. 28 (11.9%) were not assessed (5 received DOT) 50 (21.2%): not known/not answered (8 received DOT). Guidelines: All patients should have a risk assessment for adherence to TB treatment. (NCCCC)

25. TB regimens A wide range of initial TB regimens was reported:  173 (73.3%) contained isoniazid + rifampicin +pyrazinamide + ethambutol and 17 (7.2%) contained these except rifabutin instead of rifampicin.  113 (47.9%) patients were prescribed the standard 6 months IR + 2 months PE regimen.  46 (49.5%) of patients with pulmonary TB and no known drug resistance were prescribed the standard regimen. The initial TB regimen was later extended or modified for 59 (25.0%) of all patients. Guidelines: 6IR 2PE is standard recommended regimen. Use 12 month regimen for meningeal TB. (NCCCC)

26. Outcomes of TB treatment Guidelines: All outcomes recorded, 85% successful completion. (CMO) Number of patients Percent of patients Completed full course without interruption14461.0 Treatment ongoing at audit5121.6 Interrupted125.1 Transferred care within UK62.5 Died before completion62.5 Left UK while on treatment114.7 Stopped attending while on treatment, not known to have transferred care or left UK 62.5 Total236100.0

27. Outcomes of TB treatment, continued Based on data on previous slide, 80.8% of patients completed treatment successfully:  This includes 3 patients who re-started after interruption and then completed  It excludes 54 patients whose treatment was ongoing at audit. Guidelines: All outcomes recorded, 85% successful completion. (CMO)

28. Timing of HAART relative to start of TB treatment Number of patients Percent of patients HAART started more than 2 months before TB treatment 6125.8 2 weeks-2 months before145.9 Within 2 weeks before or after187.6 More than 2 weeks after starting TB treatment, but during intensive phase 5121.6 During TB treatment, after the intensive phase 3816.1 After completion of TB treatment125.1 HAART not started3615.3 Not known/not answered62.5 Total236100.0

29. HAART during TB treatment HAART regimens used for patients treated during TB treatment Number of patients Percent of patients NNRTI-based13979.0 PI-based3117.6 NRTI only63.4 Total 176100.0 Guidelines: Substitute rifabutin for rifampicin if using boosted PI. Adjust EFV dose when using with rifampicin. Avoid daily rifampicin with NVP. (BHIVA)

30. Immune reconstitution inflammatory syndrome  14 (5.9%) patients were diagnosed with IRIS, of whom 11 were treated with steroids and 1 was already on steroids.  14 (5.9%) further patients experienced some worsening of symptoms after starting HAART, but it was unclear if this was due to IRIS. 2 of these patients were already on steroids.

31. Limitations  Few TB clinics/units took part in the survey. This probably reflects the recruitment method. Better uptake might have been achieved by writing directly to trust TB leads, instead of asking HIV services to invite their corresponding TB services to participate.  Some patient data was incomplete because this was provided via HIV services, not all of whom had access to TB clinic records.

32. Conclusions In general the findings of this audit were positive, but with some areas of concern:  Some services not offering HIV testing routinely regardless of risk, although this may have changed following 2008 guidelines.  Poor documentation of TB notification, and some cases not notified.  Unacceptable delays in sputum smear results.  80.8% TB treatment completion rate did not meet 85% target.

33. Conclusions, continued  Many patients had very low CD4 counts. This partly reflected stage at diagnosis of HIV, even though nearly all patients were screened at the time of TB diagnosis.  Non-attendance/treatment refusal/non- adherence are of concern in relation to both HIV and TB.  Some patients apparently received rifampicin with PI-based HAART.  Some patients received NRTI-only ART regimens during TB treatment.

34. Conclusions, continued Other points of note are:  As expected in HIV co-infection, extrapulmonary TB was common, making diagnosis more complex.  Many patients received non-standard TB regimens. The reasons are unclear.  Practices vary as regards reporting the patient’s HIV status when notifying TB.

35. Future TB surveillance and reporting Health Protection Agency is introducing web-based Enhanced Tuberculosis Surveillance:  “..collects demographic, clinical and microbiological data on all cases of TB  “Case reports can be passed between clinics, if the patient’s care becomes transferred  “Laboratory results.. will be linked to case reports at the local level.. data from reference laboratories will be loaded into the system at frequent intervals.”

36. BHIVA Audit & Standards Committee Other current/planned activity:  Briefing on the role of primary care in HIV Data collection autumn 2009:  Casenote review and survey of management of HIV and hepatitis B/C co-infection  Survey of management of paediatric aspects of adult HIV care: ensuring testing of children of adult patients; transition for young people.