1. 1 GH Friedland, MD Tuberculosis and HIV Models for TB programmes to contribute to the delivery of ART What are the operational research questions? Gerald Friedland, MD AIDS Program Yale University School of Medicine

2. 2 GH Friedland, MD TB and HIV-two cultures Minimal TB and HIV Program needs Spectrum of collaboration/integration Case studies Operational research issues Models of TB/HIV Care

3. 3 GH Friedland, MD HIV/TB-Two Cultures TB culture: public health approach, with firmly established algorithms, fixed and standardized measures and outcomes TB services: geared for chronic care-but relatively short term, standardization, simplified regimen, epidemic control, difficulty with individual nuance and new TB diagnostic dilemmas with HIV disease HIV as an “intruder”: disrupting TB strategies and programs HIV culture: individual patient and human rights approach, guidelines but no standardization, familiar with rapid treatment paradigm changes HIV services : clinically and patient oriented with only recent emerging public health practices; lifelong treatment, limited experience with TB treatment and public health approach TB as a challenge: discomfort with treatment in HIV setting

4. 4 GH Friedland, MD Comprehensiveness Continuity Competence Compassion Cost effectiveness The Minimum for effective TB-HIV collaboration –

5. 5 GH Friedland, MD The Minimum for effective TB-HIV collaboration – the TB side Counseling and Testing for to identify HIV infected HIV/AIDS staff training/awareness Co-trimoxazole prophylaxis for TB patients who are HIV infected Mechanism for referral for antiretroviral therapy for TB-HIV co-infected patients who need it (?) Primary and secondary HIV prevention education for TB patients Patient confidentiality

6. 6 GH Friedland, MD Active TB case finding for all HIV infected patients TB staff training/awareness Mechanism for referral for Dx and TB treatment(?) Mechanism for continuation of HIV treatment Tuberculin skin testing (TST) for HIV infected? INH preventive therapy (IPT) for TST+ TB transmission prevention Patient confidentiality The Minimum for effective TB-HIV collaboration – the HIV side

7. 7 GH Friedland, MD –Although delivery models differ, outcomes should be identical –TB treatment success- cure/completion of therapy –Reduction in HIV disease progression and mortality –Decrease in transmission of both diseases Models of TB/HIV Care OUTCOMES

8. 8 GH Friedland, MD Need for many models One model may not fit all countries Differences in HIV and TB prevalence Differences in history, resources, culture, expertise Differences in feasibility One model may not fit one country Urban vs. rural TB clinic vs. primary care clinic Logical to maximize/exploit existing site infrastructure Hospitals, clinics, existing TB DOTS and HIV VCT programs, nascent HIV programs, available human resources Models of TB/HIV Care

9. 9 GH Friedland, MD Current and Optimal TB and HIV Program Paradigms Current TB and HIV Programs Paradigm Optimal TB and HIV Programs Paradigm National TB Program HIV Services VCT OI Px Antiretrovirals Adherence Support National HIV Program National HIV Program Communication Collaboration TB Services Sputum collection DOT Treatment Support Contact Tracing LTBI Treatment TB Services Sputum collection DOT Treatment Support Contact Tracing LTBI Treatment HIV Services VCT OI Px Antiretrovirals Adherence Support National TB Program Communication Collaboration

10. 10 GH Friedland, MD Which model of collaboration ? TBHIV/AIDS TB AIDS TB/AIDS Separate TB/ HIV patients referral Full One stop service for TB- HIV co-infected TB AIDS Partial Some mixing

11. 11 GH Friedland, MD 1.HIV programs learn lessons from TB program with little to no integration of services Malawi 2. TB programs serve as site for some integration and collaboration of services START- Durban, Sizonqoba-Tugela Ferry 3.HIV and TB programs organized with full integration of services Khayelitsha Models of TB/HIV Care and Treatment

12. 12 GH Friedland, MD Malawi model Anthony D Harries, HIV/AIDS Unit, Ministry of Health, Malawi HIV program learns from and uses DOTS model No true integration of TB and HIV care Appropriate in Malawi –Poor infrastructure with very few physicians –Large population with immediate need to start a significant number of patients on ART 1 million people infected with HIV 170,000 people needing HAART

13. 13 GH Friedland, MD Apply Tuberculosis Control structure to HIV treatment and care is one “model” Standardised diagnosis and case finding (smear microscopy and well defined types of TB) Standardised treatment (three treatment categories to cover all types of TB) Standardised recording and reporting system (treatment cards, registers, cohort analysis, monitoring) Standardised system of drug procurement Management by paramedical officers Free drugs for patients

14. 14 GH Friedland, MD Standardised Treatment Outcomes TB Programme: Cured Treatment completed Dead Defaulted Failed Transferred out ART delivery: Alive and on ART Dead Defaulted Stopped treatment Transferred out

15. 15 GH Friedland, MD TB programs serve as site for some integration and collaboration of services The START study Demonstrate effectiveness and safety of HIV/TB integrated treatment strategy in an urban, resourced setting- Prince Zulu Communicable disease clinic, Durban, KwaZuluNatal, South Africa Partnership of: –I kithweni Muncipality Department of Health –CAPRISA- US NIH –Nelson R Mandela School of Medicine –Yale University, Columbia University –Irene Diamond Fund, Doris Duke Charitable Foundation

16. 16 GH Friedland, MD START-Pilot  TB program staff strengthened  Patients with active TB offered HIV counseling & testing  ONCE-DAILY ART (DDI, 3TC, EFAVIRENZ) given concomitantly with standard TB DOT regimen (INH, RIF, ETH, PZA) 5 d/wk with weekend ART self administration  Adherence training and social support emphasized  Transition to ART self-administration at TB Rx completion- Referral to HIV Clinic  Assessment of viral load, CD4, mortality, side effects and toxicities  Assessment of acceptability and cost

17. 17 GH Friedland, MD

18. 18 GH Friedland, MD Pilot START Results Mean Viral load and CD4 change over 21 months Self administration

19. 19 GH Friedland, MD TB programs serve as site for some integration and collaboration of services Sizonq’oba study Demonstrate effectiveness and safety of HIV/TB integrated treatment strategy in a rural, resource-poor setting, Tugela Ferry, KwaZuluNatal, South Africa

20. 20 GH Friedland, MD The Sizonq’oba rural study Project outline: –Strengthening of TB DOT program –Merging TB DOT and Home Based Care Program –Training of physicians, nurses, community health workers-TB and HIV –TB pts identified in hospital, receive VCT –Once-daily DOT ART added to Home-based /TB DOT program and given with TB meds in community –Community and family social and adherence support –Community and clinical monitoring for benefit and risk. –Transition to self-administration at completion of TB therapy –Cost effectiveness study –Sexual risk study –Separate records, mostly separate staff, program monitoring, reporting, funding

21. 21 GH Friedland, MD adherence support group

22. 22 GH Friedland, MD Integrating 2 vertical services : HIV/AIDS and TB services, Khayelitsha, South Africa David Coetzee, Eric Goemere 2000: opening HIV/AIDS clinics in public services, next to the TB clinic 2001: first HAART patient … > 1400 patients 9-05 2002: VCT re-enforced in TB service and easier access to HAART 2003: merging both buildings and stepwise integration of HIV and TB services

23. 23 GH Friedland, MD Objectives of TB/HIV integration For TB patients To stimulate VCT among TB clients 47 % counselled and 87 % accepted testing-(8-40 Gugulethu ) 63 % co- infection To accelerate access to HAART for TB/HIV co-infected To reduce TB incidence among HIV patients To improve TB diagnostic algorithms To increase adherence and cure rate among TB patients by using the HIV adherence tools HIV 95% (36 mos vs TB ~75% Rx completion HIV adherence tools and counselors

24. 24 GH Friedland, MD Objectives of TB/HIV integration For HIV patients To have an easier access to TB diagnosis and treatment To develop a one stop service To benefit from existing TB network to support HIV For the health services To pool TB and HIV staff and integrate training To improve staff morale

25. 25 GH Friedland, MD develop a one stop service Both building have been merged 2 different patient flows –TB non co-infected :2 clinical visit/episode –HIV and co-infected :monthly clinical visit A positive impact on TB/HIV patients: –Reduced queuing time –Improved clinical monitoring –Allow adjustment for treatment interactions A negative impact on non-co-infected TB cases

26. 26 GH Friedland, MD pool TB and HIV staff and integrate training Tb and HIV staff now able to rotate between services No recruitment out of existing TB service but rather re-enforcement Improved staff morale with improved treatment outcomes New clinical career path for TB staff Renewed doctor’s interest in TB

27. 27 GH Friedland, MD Operational Issues in TB and HIV Care How to improve diagnosis of HIV in TB patients Expand voluntary counseling and testing Provide rapid point of care HIV testing Provide routine counseling and testing in TB patients Encourage provider based testing Perform opt out vs. opt in testing How to improve diagnosis of TB and LTBI in HIV patients Develop algorithms for clinical assessment of TB disease Develop and use of rapid diagnostic tests

28. 28 GH Friedland, MD Operational Issues in TB and HIV Care How to improve treatment of HIV in TB patients Determine best setting(s) to initiate and continue antiretroviral therapy in co-infected patients Degree of integration/collaboration Elucidate mechanisms to support adherence Define the role of DOT in antiretroviral therapy Identify most effective DOT dose, intensity and duration Determine most appropriate person(s) to provide treatment Determine role of non-physician health care workers Determine role of community and family Determine training needs Determine how to minimize occupational/nosocomial risk from HIV and TB

29. 29 GH Friedland, MD Operational Issues in TB and HIV Care How to improve treatment of HIV in TB patients Determine optimal time to start antiretroviral therapy Identify optimal antiretroviral regimens to use Determine how rifampin interactions with antiretroviral agent effect clinical outcomes Identify proper dose of antiretrovirals in the presence of rifampin Conduct observational and clinical trials to assess treatment effectiveness in co-infected patients Establish appropriate schedules for toxicity and efffectiveness monitoring

30. 30 GH Friedland, MD Operational Issues in TB and HIV Care How to improve the treatment of TB in HIV patients Determine ways to strengthen existing TB programs Evaluate measures of treatment success Examine role of newer diagnostic tests to assess treatment success. Determine optimal duration of therapy How to accommodate differing TB and HIV traditions and practices