1. DOT: Can we learn from tuberculosis in the HIV field? Moïse Desvarieux, MD PhD Chaire d’Excellence ANR, Inserm UMR S 707 Associate Professor of Epidemiology, Columbia University

2. Key differences in HIV vs TB TB DOT is public health mandateDOT is public health mandate –Physical to pharm quarantine –Therapy leads to non- infectiousness –Casual transmission TB treatment 6-12 mo.TB treatment 6-12 mo. Twice weeklyTwice weekly HIV No public health mandate for treatmentNo public health mandate for treatment –Sometimes for transmission –Not entirely clear, nor as fast –Sexual transmission Lifelong treatmentLifelong treatment Best is once dailyBest is once daily

3. Biology and infection dynamics are different TB Long generation time and slow emergence of drug resistanceLong generation time and slow emergence of drug resistance MDR is iatrogenicMDR is iatrogenic No substantial effect of foodNo substantial effect of food HIV Short generation time and error-prone reverse transcriptase, rapid emergence of resistanceShort generation time and error-prone reverse transcriptase, rapid emergence of resistance Important effect of food on bioavailabilityImportant effect of food on bioavailability

4. May DOT for ARV increase drug pressure to a critical level where the risk of drug resistance is subsequently highest?May DOT for ARV increase drug pressure to a critical level where the risk of drug resistance is subsequently highest?

5. But where does Directly Observed Therapy for Tuberculosis stand?But where does Directly Observed Therapy for Tuberculosis stand?

6. Universal paradigm? One size-fits-all or custom-made? Home or clinic/hospital based? Family member or community worker?

7. Source: Volmink J, Garner P, et al Directly Observed Therapy for Treating Tuberculosis, 2007 Cochrane Review of DOT for Tuberculosis: Impact on Cure

8. Source: Volmink J, Garner P, et al Directly Observed Therapy for Treating Tuberculosis, 2007 Cochrane Review of DOT for Tuberculosis: Impact on Cure or treatment completion

9. Source: Volmink J, Garner P, et al Directly Observed Therapy for Treating Tuberculosis, 2007

10. Cochrane Review of DOT for Tuberculosis: Impact of location of administration on cure

11. Source: Volmink J, Garner P, et al Directly Observed Therapy for Treating Tuberculosis, 2007 Cochrane Review of DOT for Tuberculosis: Impact of location of administration on cure or treatment completion

12. Source: Volmink J, Garner P, et al Directly Observed Therapy for Treating Tuberculosis, 2007

13. Cochrane Review of DOT for Tuberculosis: Impact of family member versus community health worker

14. Source: Kruk ME, Schwalbe NR, Aguiar CA et al Timing of Default From Tuberculosis Treatment: A Systematic Review 2008. Clearly, timing seems to matter in TB…

15. Clinical trials of DOT for HIV should address Retention on therapy, virologic and immunologic outcomes to at least one yearRetention on therapy, virologic and immunologic outcomes to at least one year Development of drug resistance (in spite of our a priori hypothesis)Development of drug resistance (in spite of our a priori hypothesis) Cost-effectiveness (time and labor intense)Cost-effectiveness (time and labor intense)

16. But what groups of patients?But what groups of patients? –All –New patients –Low motivational state and Late-stage disease (Bangsberg) Implications (and what is it in TB?)Implications (and what is it in TB?)

17. In Tuberculosis, the priority for treatment is the most contagious formIn Tuberculosis, the priority for treatment is the most contagious form However, virologic tool for adherenceHowever, virologic tool for adherence

18. Social contextts The epidemics do cross but not perfectlyThe epidemics do cross but not perfectly Impact of private sectorImpact of private sector As HIV moves to primary care, what impact on supervision?As HIV moves to primary care, what impact on supervision?

19. Source: Macq J, Torfoss T, Getahun H. et al Patient empowerment in Tuberculosis Control: Reflecting on Past Documented Experiences. 2007

21. Conclusions Yes we can learn from TB experience with DOTYes we can learn from TB experience with DOT But do we really want to learn?But do we really want to learn? What are our intrinsic beliefsWhat are our intrinsic beliefs Targeting is probably the keyTargeting is probably the key Impact of primary care and private sector and the end of exceptionalismImpact of primary care and private sector and the end of exceptionalism