1. TB/HIV Research Priorities: TB Preventive Therapy

2. What We Know INH preventive therapy with demonstrated efficacy in HIV+/PPD+, HIV+/PPD unknown Rifampicin-containing regimens equivalent in efficacy to INH preventive therapy Areas for which there is data, but more is needed –Excluding TB disease (pulmonary, extra-pulmonary –Drug regimen in areas of elevated INH resistance –Adherence –Feasibility –Cost-effectiveness, resource needs –Barriers to uptake, e.g. short-term benefit not great, long- term risk of resistance, cost-benefit relative to ART

3. Research Priorities: Patient Level In patients with HIV infection receiving a gold standard bacteriologic evaluation, what minimum components of a screening evaluation (e.g., signs, symptoms, CXR, smear) are sufficient to rule out TB disease? –When implemented at a program level, what proportion of missed cases is acceptable to achieve public health benefit?

4. Research Priorities: Patient Level In patients receiving currently recommended TB preventive therapy regimens, what interventions at the community, clinic, and/or patient-level are most effective in promoting sufficient adherence to TB preventive therapy?

5. Research Priorities: Patient Level What is the efficacy of, optimum duration for, and optimum time to start TB preventive therapy in HIV-infected patients receiving ART? What sub-groups of patients are likely to receive maximal benefit? –Stratification by cytokine-based diagnosis (e.g., Quantiferon) –Stratification by HIV stage

6. Research Priorities: Patient Level What is the efficacy of TB preventive therapy in children and infants?

7. Research Priorities: Population Level Which macro-level factors are responsible for the low uptake of TB preventive therapy by Ministries of Health? How can these factors best be addressed? In settings of high HIV prevalence, what is the contribution of TB preventive therapy to the control of TB, when compared with or when added to other interventions, e.g. active case finding, anti-retroviral therapy?

8. Research Priorities: Population Level Has the Botswana national TB preventive therapy program (or other national TB preventive therapy programs) been successful in achieving its desired objectives? What lessons can be extrapolated to international policy?

9. Research Priorities: Population Level Does the efficacy of INH preventive therapy vary in regions or countries that have not been as well studied (e.g., Eastern Europe / CIS)? Is the efficacy of INH preventive therapy reduced in populations with elevated rates of background INH resistance? Which alternative preventive therapy regimens are efficacious?

10. Research Priorities: Population Level How can INH preventive therapy be safely and effectively delivered in settings with IDU-driven epidemics? Which factors are responsible for the low uptake of TB preventive therapy among HIV-infected pregnant women?

11. Research Priorities: Population Level Should secondary preventive therapy (i.e., TB preventive therapy administered after completion of TB disease treatment) be adopted as policy? And if not, what evidence is needed to adopt it as policy?

12. How To Do the Research: Many Studies Ongoing! Alternative regimens Alternative durations Effectiveness of mass-preventive therapy +/- intensified case finding Effectiveness in patients receiving ART

13. What to Do in the Meantime Continue current policy: a minimum package of care at individual level Await ongoing studies and modify policy as evidence emerges Promote adherence based on existing evidence

14. Summary: Patient Level Optimum algorithm to exclude TB disease Added benefit to IPT in patients receiving ART Sub-groups of patients likely to benefit Effectiveness in infants and children

15. Summary: Population Level Macro-level barriers to implementing IPT and mechanisms to overcome barriers Outcomes of national IPT program in Botswana: lessons learned Effectiveness in special populations and regions with elevated INH resistance