DOT: Can we learn from DOT: Can we learn from tuberculosis in the HIV tuberculosis in the HIV

field?field?

Moïse Desvarieux, MD PhDMoïse Desvarieux, MD PhD

Chaire d’Excellence ANR, Chaire d’Excellence ANR,

Inserm UMR S 707Inserm UMR S 707

Associate Professor of Associate Professor of Epidemiology, Columbia UniversityEpidemiology, Columbia University

Key differences in HIV vs TB Key differences in HIV vs TB

TB

• DOT is public health DOT is public health mandatemandate– Physical to pharm Physical to pharm

quarantinequarantine– Therapy leads to non-Therapy leads to non-

infectiousnessinfectiousness– Casual transmissionCasual transmission

• TB treatment 6-12 mo.TB treatment 6-12 mo.• Twice weeklyTwice weekly

HIV

• No public health No public health mandate for treatmentmandate for treatment– Sometimes for Sometimes for

transmissiontransmission– Not entirely clear, nor as Not entirely clear, nor as

fastfast– Sexual transmissionSexual transmission

• Lifelong treatmentLifelong treatment• Best is once dailyBest is once daily

Biology and infection dynamics are different

TB

• Long generation time Long generation time and slow emergence of and slow emergence of drug resistancedrug resistance

• MDR is iatrogenicMDR is iatrogenic• No substantial effect of No substantial effect of

foodfood

HIV

• Short generation time Short generation time and error-prone reverse and error-prone reverse transcriptase, rapid transcriptase, rapid emergence of emergence of resistanceresistance

• Important effect of food Important effect of food on bioavailabilityon bioavailability

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

• But where does Directly Observed But where does Directly Observed Therapy for Tuberculosis stand?Therapy for Tuberculosis stand?

Universal paradigm?

• One size-fits-all or custom-made?

• Home or clinic/hospital based?

• Family member or community worker?

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

Cochrane Review of DOT for Tuberculosis: Cochrane Review of DOT for Tuberculosis: Impact on CureImpact on Cure

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

Cochrane Review of DOT for Tuberculosis: Cochrane Review of DOT for Tuberculosis: Impact on Cure or treatment completionImpact on Cure or treatment completion

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

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

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

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

Cochrane Review of DOT for Tuberculosis: Cochrane Review of DOT for Tuberculosis: Impact of location of administration on cure or treatment completionImpact of location of administration on cure or treatment completion

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

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

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

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…Clearly, timing seems to matter in TB…

Clinical trials of DOT for HIV should address

• Retention on therapy, virologic and Retention on therapy, virologic and immunologic outcomes to at least one immunologic outcomes to at least one yearyear

• Development of drug resistance (in Development of drug resistance (in spite of our a priori hypothesis)spite of our a priori hypothesis)

• Cost-effectiveness (time and labor Cost-effectiveness (time and labor intense)intense)

• But what groups of patients?But what groups of patients?– AllAll– New patientsNew patients– Low motivational state and Late-stage Low motivational state and Late-stage

disease (Bangsberg)disease (Bangsberg)

• Implications (and what is it in TB?)Implications (and what is it in TB?)

• In Tuberculosis, the priority for In Tuberculosis, the priority for treatment is the most treatment is the most contagiouscontagious form form

• However, virologic tool for adherenceHowever, virologic tool for adherence

Social contextSocial contexttsts

• The epidemics do cross but not The epidemics do cross but not perfectlyperfectly

• Impact of private sectorImpact of private sector

• As HIV moves to primary care, what As HIV moves to primary care, what impact on supervision?impact on supervision?

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

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

ConclusionsConclusions

• Yes we can learn from TB experience Yes we can learn from TB experience with DOTwith 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 Impact of primary care and private sector and the end of exceptionalismsector and the end of exceptionalism