1. Challenges of service integration: the TB model Linda-Gail Bekker The Desmond Tutu HIV Centre, Faculty of Health Sciences, University of Cape Town, South Africa AIDS Conference Melbourne July 2014

2. Global TB in 2012 33 million HIV infected 1/3 have TB 8.6 million new cases of TB globally 13% co-infected with HIV. 1.3 million deaths (320 000 deaths in HIV/TB) SA: >300 cases notified annually (3 rd largest number) 933/100 000 Largest number TB/HIV co-infected (65%)

3. TB incidence rates : 2012

5. HIV prevalence/ new TB cases : 2012

6. Number of HIV-infected persons receiving antiretroviral treatment (ART) and percentage of persons receiving concomitant tuberculosis treatment in Africa 2002-2007

7. HIV in a sea of TB/TB in a sea of HIV In our TB clinics: reason for HIV testing and diagnosis of HIV – Similar symptoms – Now an indication for referral for ART In our HIV Clinics: TB not always symptomatic but must be actively investigated for. – Indication to start ART regardless of CD4. In our primary health clinics : both conditions often present simultaneously

8. Annual TB notifications

9. The numbers of tuberculosis notifications, stratified by 5-year age groups and HIV-status

10. 67% 47% 22% 8% Percentage of patients starting HAART TB Burden Prior to Initiation of HAART

11. A:TB Incidence by CD4 without HAART B: TB Incidence by CD4 with HAART A: Cape Town AIDS CohortB: Cape Town ART Cohort A: Holmes, Wood, Badri, et al JAIDS 2006 B: Lawn, Myers, Edwards Bekker, Wood. AIDS 2009

12. Good to get TB/HIV positive people onto ART 0 10 20 30 40 50 60 70 80 90 100 Percentage of patients with CD4 below contour 04812162024 28 3236404448 Duration of ART (months) 1000 cells/ul 500 cells/ul 200 cells/ul TB rate 9.3-16.8 TB rate >4.2-5.5 TB rate = 1.5

13. Presentation of TB and HIV co-infection: 1.TB diagnosed before starting ART 2.A patient develops TB while on ART 3.A patient who has defaulted ART develops TB

14. Reason for urgency Patients known to be HIV positive who develop TB and are not diagnosed or not treated – morbidity and mortality In addition they are a TB risk to others Patients known to have TB who are diagnosed HIV+ need ART (recommend: <8weeks) Delays result in morbidity and mortality – Number of RCTs – lower CD4 groups

15. 200920102011Total TB cases (n)25,84126,10425,554 77,499 HIV Positive (%)49.750.450.950.3 HIV Negative (%)44.946.847.146.3 HIV status unknown (%)5.42.92.03.4 HIV prevalence in the PHC TB service-CT 2009-2011

16. Survival stratified by ART status for patients with CD4 counts < 350 Time (Days) Median Time to Death Started ART 71days (IQR: 38-119) On ART at TB diagnosis 60 days (IQR: 26-118) No ART 54 days (IQR: 25-104) Half of the deaths in patients who do not start ART occur within 8 weeks

17. Summary: In the PHC TB service in Cape Town 50% of adult TB patients are HIV positive 82% have CD4 counts below 350 91% of deaths in HIV+ve patients occur in patients with CD4 counts below 350 32% of patients with CD4 counts <350 did not start ART during TB treatment (2009 – 2011) Mortality for patients on ART was 50% less than patients not on ART for CD4 counts <350 Median time to death for patients not on ART is +/- 8 weeks

18. A median delay of over 16 weeks between start of TB treatment and start of ART was noted for patients referred from TB facilities to the Gugulethu ART clinic. This was reduced to 41 days if TB diagnosis was made at the ART clinic. 1 Median delay of 2.66 months (+/- 74 days) between start of TB Rx and start of ART in clinics in CT (Masiphumulele, Gugulethu and in Khayelitsha) between 2002 and 2008 2 1 Lawn et al BMC Infect Dis 2011, 2 Lawn et al JAIDS 2011, Delays occur moving between the facilities

19. Primary Health care setting TB clinic HIV CT Referral to ART services HIV/ART clinic TB ACTIVE CF Referral to TB services Missed opportunities: HCT, ACF, IPT, CTX Inherent DELAYS and LOSS TO FOLLOW UP Missed opportunities: HCT, ACF, IPT, CTX Inherent DELAYS and LOSS TO FOLLOW UP

20. HIV only HIV/TB TB only ART for life TB treatment for 6-9 months TB treatment for 6-9 months TB treatment for 6-9 months TB treatment for 6-9 months The primary health care setting Overburdened clinics and overburdened patients

21. By “integrating” services (the 4 th I) Tackle the 3 Is in HIV+: – Intensified case finding (delay freeTB Rx) – (INH) Prophylaxis – Infection control But other advantages in TB suspects and patients: – Test all for HIV – Offer ART without delays (5 th I !!)- ? All CD4s? – Streamline services to provide both medications hassle free- quality of services (?reduce LTFU).

22. Variety of Models: Co-location of services in the same clinic with referral between services on site. Co-location of services with shared management discussions and shared adherence support services. Integration of services with HIV/ART services managing TB Integration of services with TB services managing HIV/ART HIV/ART/TB clinics de novo.

23. A model for service integration

24. DOTS visits: Post integration of services

25. Systematic review :2010 136 papers describing models of integration None RCTs and very few with TB or HIV outcomes Models based on referral only easiest to implement – Referrals may fail, communication key and often poor. More integration needs more staff buy in and training. Grant, et al 2010)

26. Barriers and enablers to integration: Service users unconvinced of need for more testing! Those referred battling to find referral services Fragmentation of services Poor communication between services Data systems inadequate for coordinated care Infrastructure poor for privacy Staff not motivated to take on “more” Supply of drugs and test kits unreliable Joint staff training and support Identifying staff “champion”

27. In the Nyanga CHC which has co-located TB and ART clinics 1 – 19.7% of ART eligible TB patients did not start ART – Median delay of 51 days from TB Rx start to ART start In an integrated ART/TB clinic in Khayelitsha 2 – 34/100 TB patients ART eligible patients did not start ART – Median delay of 58 days from TB Rx start to ART start Town 2 Clinic after ART was introduced into a TB service 3 – Median delay of 75 days between TB and ART initiation post integration (decreased from 147 days) 1 Nglazi et al S Afr Med J 2012, 2 Pepper et al PLoS One 2011, 3 Kershberger et al PloS One 2012 Simply Integrating TB and ART services doesn’t simply solve uptake and delays.

28. Pilot analysis in 5 clinics in CT vs Standard TB program Caldwell et al, 2010

29. Qualitative data Preferred by field adherence supporters –Better relationships with patients and better outcomes Preferred by patients –Less transport and “hassle” factors –Better understanding of both diseases Preferred by nursing staff. –Less “DOTS” burden and improved outcomes.

30. TB outcomes in facilities in CT: A: 13 integrated and B: 4 single service facilities. N= 13 542 newly registered patients (66% HIV+). Kaplan, et al 2014

31. Conclusions There is a burden of co-infection especially in areas where TB and HIV are hyperendemic Both diseases require long term adherence to medications that can interact. Outcomes are improved when TB/HIV is managed actively: 3 Is – ICF, IPT, IC (and now add IS) Delays in treatment of both HIV and TB leads to increased morbidity and mortality. Pragmatic to co-locate and move toward integration paying attention to infection control. More research required that measures outcomes including TB cure, viral control and any risks (IC).

32. Thanks Sten and Paolo Richard Kaplan (DTHC) Judy Caldwell and CoCT Steve Lawn