1. HIV and Hepatitis B/C Co-infection Audit Audit & Standards Sub-Committee: M Johnson (chair), M Backx, C Ball, G Brook, D Churchill, A De Ruiter, S Ellis, A Freedman, L Garvey, P Gupta, K Foster, V Harindra, C O’Mahony, E Monteiro, E Ong, K Orton, R Pebody, F Post, C Sabin, A Schwenk, A Sullivan, R Weston, E Wilkins, D Wilson, M Yeomans

2. Background Chronic viral hepatitis: Global problem 350 million HBV and 170 million HCV UK prevalence 0.3% HBV, 0.44% HCV Many undiagnosed HIV and hepatitis B/C co-infection: Similar transmission routes Estimates HIV/HBV 3-10% in UK, higher elsewhere HIV/HCV rates vary by risk group Accelerated liver disease progression Increased risk of drug hepatotoxicity

3. BHIVA Guidelines (2005) Screening of all HIV+ patients: At HIV diagnosis, non-immune HBV should be vaccinated Thereafter check serology and anti-HBs titre annually (aim > 100 IU/L) HIV+ patients with chronic HBV / HCV: Appropriately vaccinate (HAV / HBV) Discuss avoidance of alcohol, transmission prevention Trace and vaccinate contacts Clinical assessment, LFT and clotting. If significant liver disease subjects should be under joint care of HIV team and Hepatologist Screen for HCC in cirrhotics 6-monthly

4. For HIV/HBV patients: HBeAg, HBV DNA Consider biopsy if active replication >2000 IU/mL (10 4 copies/mL) Consider treating HBeAg+ve (or high ALT + HBV DNA) TDF but not 3TC/FTC as sole anti-HBV agent (within HAART) Consider including TDF + 3TC/FTC in those on HAART Note Guidelines 2010: Recommend treatment if fibrosis present (at any HBV DNA level) or if HBV DNA >2000 IU/mL (CD4 based treatment algorithms) Liver imaging and biopsy or non-invasive fibrosis assessment BHIVA Guidelines (2005)

5. For HIV/HCV patients: HCV RNA and genotype Consider biopsy to stage disease Consider HCV treatment especially if moderate disease (mild may defer) Treat HCV before commencing HAART if CD4+ >200 cells/uL Note Guidelines 2010: Liver imaging and biopsy or non-invasive fibrosis assessment Treat HCV before HAART if CD4+ >350 cells/uL BHIVA Guidelines (2005)

6. Aims and Methods To describe care arrangements for HIV and hepatitis co-infected patients in the UK To assess adherence to BHIVA Guidelines (2005) Survey Sent to HIV Clinical Lead at each site Questions regarding type of centre, caseload, service provision for co-infected patients, issues or concerns Case note review Computerised questionnaire collecting clinical data and details of HIV and hepatitis treatment

7. Methods Inclusion criteria: HIV Ab +ve adult patients Attended HIV services between April-September 2009 HBsAg +ve and/or HCV Ab +ve Exclusion criteria: HIV diagnosis pre-1999 Hepatitis cleared prior to HIV diagnosis HBV DNA or HCV RNA negative at time of first positive hepatitis serology and never subsequently positive

8. Clinic Survey

9. Results - response Clinic survey 140 sites responded to the survey 68 (49%) Outpatient HIV department 59 (42%) HIV centre 13 (9%) neither

10. Arrangement for providing hepatitis treatment NB totals do not add to 100% because respondents could select more than one option. % sites

11. Hepatitis testing at sites

12. Annual hepatitis testing in HIV+ subjects BHIVA Guidelines: Check hepatitis B/C serology or titre annually (2005) N (%) of sites testing at least annually HBsAg or anti-HBc in non-immune100 (71) anti-HBs titre in vaccinated84 (60) HCV antibody in non-infected92 (66) HCV PCR in non-infected11 (8)

13. Availability of tests N (%) sites where availability limited N (%) sites where test unavailable HBV DNA7 (5)0 (0) HCV RNA7 (5)1 (1) HCV genotype10 (7)2 (1) Note:15 sites in total reported some test restrictions (site not included if all co-infected patients referred elsewhere) BHIVA Guidelines: Check HBV DNA if HBsAg+ve (2005)Check HCV RNA and genotype if HCV Ab+ve

14. Issues and concerns Positive comments: 39 sites - good liaison between HIV and Hepatology Co-infection clinics and specialist nurses appreciated, where available Concerns: 10 sites - communication could be improved 7 sites - concerns about referral delays/waiting times 4 sites - networks could be strengthened Other concerns: Lengthy travel distances, lost referrals, lack of language support, high DNA rates

15. Patient case note review

16. Patient characteristics 975 eligible patients (121 sites)

17. Patient demographics

18. Patient characteristics N (%) unless otherwise statedHBVHCV Total477522 Male307 (64)411 (79) HIV-acquisition risk group Heterosexual MSM IDU Other 314 (66) 113 (24) 6 (1) 14 (3) 94 (18) 197 (38) 166 (32) 38 (7) On HAART at time of audit408 (86)414 (79) Latest CD4 + count Above 350 201-350 200 or below 296 (62) 107 (22) 69 (15) 356 (68) 101 (19) 51 (10) First CD4 + count Above 200 200 or below 191 (40) 213 (45) 292 (56) 119 (23) Some totals add to less than 100% due to missing data

19. Prevention and health promotion

20. Documented discussion alcohol: 50% overall, (HBV 41%, HCV 58%) For majority the most recent documented discussion 2008-9 Transmission reduction: 58% documented evidence of discussion BHIVA Guidelines: Documented discussion alcohol avoidance and (2005)transmission reduction

21. Prevention and health promotion Contact tracing: 53% HBV cases had attempts to trace household/sexual contacts for immunisation 52% HCV cases had attempts to trace sexual/parenteral contacts for testing After excluding those known to be childless, evidence that 75 (40%) female patients had children tested for hepatitis BHIVA Guidelines: Documented discussion contact tracing (2005)and vaccination

22. Immunisation BHIVA Guidelines: Hepatitis A immunisation for all susceptible (2005)co-infected subjects % subjects

23. Immunisation BHIVA Guidelines: Hepatitis B immunisation for all susceptible (2005)HCV -infected subjects % subjects

24. Immunisation BHIVA Standards: Hepatitis B immunisation for all susceptible (2005)HCV -infected subjects % subjects

25. Staging hepatitis disease

26. Assessment using PCR tests BHIVA Guidelines: Check HBeAg and HBV DNA if HBsAg+ (2005)Check HCV RNA and genotype if HCV Ab+ % subjects

27. Investigation of fibrosis Biopsy / fibrosis assessment: 205 (21%) all HBV/HCV patients had liver biopsy 32 (3%) had declined 354 (36%) patients had had biopsy, elastography or serum fibrosis markers assessed (47% of HCV, 25% of HBV) BHIVA Guidelines: HCV: consider biopsy to stage disease (2005)HBV: consider if HBeAg+ (or high DNA and ALT) 2010 Guidelines :biopsy / fibrosis assessment for all HBV/HCV

28. Markers of significant liver disease* Markers of significant liver disease: 202 (21%) had ever had markers consistent with significant liver disease (134 HCV, 58 HBV, 10 HBV/HCV) ALT >5x ULN only marker for 126, including 56 acute HCV cases Of those with disease markers other than isolated ALT: 49 (64%) were under the care of a hepatologist / liver specialist 67 (88%) had documented management plan for care of HIV and liver disease *Markers were: cirrhosis, deranged clotting, serum ALT >5x ULN, ascites, varices, splenomegaly, evidence of hepatocellular carcinoma *Markers were: cirrhosis, deranged clotting, serum ALT >5x normal, ascites, varices, splenomegaly, evidence of HCC BHIVA Guidelines: Clinical assessment for evidence of cirrhosis (2005)LFT and clotting

29. HCC screening in cirrhotic patients HCC screening: 33 (77%) of 43 cirrhotic patients had USS and AFP in past year 3 patients had HCC (2 HCV, 1 HBV) BHIVA Guidelines: 6-monthly USS and AFP if cirrhotic (2005)

30. Hepatitis treatment

31. Treatment of HBV 477 HBV co-infected patients 415 (87%) on anti-HBV therapy 413 on HAART BHIVA Guidelines: Consider treatment for HBeAg+ve subjects (2005)(or high HBV DNA+ALT) 62 (13%) not on anti-HBV therapy 1 on HAART

32. 415 on HBV therapy BHIVA Guidelines: 3TC/FTC not sole anti-HBV agent (2005)If using HAART consider including TDF + 3TC/FTC Most recent HBV DNA on 3TC alone: undetectable in 16, 2000 IU/ml in 2 (TDF intolerance in 3 of 5 detectable) 26 (6%) 3TC alone 371(89%) TDF + FTC/3TC 11 (3%) TDF alone Treatment of HBV 7 (2%) other drugs 3 entecavir + 3TC/FTC 2 adefovir + 3TC 1 adefovir + telbivudine 1 adefovir

33. Treatment of HBV BHIVA Guidelines: Consider treatment for HBeAg+ve (2005)(or highDNA+ALT) 62 patients not on HBV therapy 16 (26%) HBeAg +ve Most recent HBV DNA: 16 >2000 IU/mL 26 detectable <2000 IU/ml 11 undetectable 9 unavailable Reasons given for not treating HBV: 11 assessment/referral in process 4 patient declined/wished to delay 4 poor attendance/adherence 16 considered unnecessary

34. Treatment of HCV 522 HCV co-infected patients 225 (43%) past or current HCV therapy BHIVA Guidelines: Consider treatment especially if moderate disease (2005)Treat HCV before starting HAART if CD4+ >200 297 (57%) no HCV therapy

35. Treatment of HCV Reasons given for non-treatment: Patient declined (19%) Clinical decision- genotype 1 or 4 with mild liver disease (17%) Referral/assessment in process (16%) Poor attendance (15%) Spontaneous clearance (9%) Mental illness (7%) Low CD4/waiting to stabilise on HAART (5%) Others included current/planned pregnancy, alcohol/drugs, medical/co- morbidity and social issues BHIVA Guidelines: Consider treatment especially if moderate disease (2005) Treat HCV before starting HAART if CD4+ >200 297 (57%) no HCV therapy

36. Conclusions

37. Overall audit achieved excellent participation Majority of co-infected patients diagnosed and managed according to BHIVA Guidelines Areas of concern: Hepatitis testing Approximately a third of sites do not re-test serology / titres annually Failure to vaccinate non-immune patients: 13% for HAV and 5% for HBV Areas of concern: Prevention and health promotion Documented discussion on alcohol avoidance and transmission reduction only in ~50%

38. Conclusions Areas of concern: management of co-infected patients 64% co-infected patients had not had liver biopsy or fibrosis assessment ?wider availability / awareness non-invasive tests Some patients with markers of significant liver disease were not under the care of a liver specialist Some cirrhotic patients had not been screened for HCC within past year 6% of HBV/HIV patients on anti-HBV treatment were on 3TC monotherapy, some with detectable HBV DNA

39. Conclusions

40. Follow-up of TB co-infection audit Short questionnaire sent to participating sites 6 months after audit results 63 (48%) sites responded 50 (79%) discussed results within HIV department Of sites where TB managed by other teams, 15 (48%) had discussed results with relevant colleagues Comments: some improvements since audit, ongoing concerns regarding HIV-testing for all TB cases and delays in processing sputum smears Recommend: All sites should discuss results within HIV department and with relevant colleagues / departments