1. C R E A E Consortium to Respond Effectively to the AIDS-TB Epidemic
An International Research Partnership
Supported by the Bill and Melinda Gates Foundation

3. DOTS and TB Control in Botswana
National TB Control Program – DOTS
Cases diagnosed by microscopy
All therapy supervised, short course rifampin-based
No drugs available outside program
High rates of treatment completion (>90%)
Low rates of drug resistance (<2%)
A highly successful medical intervention
Kenyon et al. Int J TB Lung Dis 1999;3:4-11

4. TB Incidence and HIV Prevalence, Botswana
Failure of a “Successful” DOTS Program to Control TB
Kenyon et al., Int J TB Lung Dis 1999;3:4-11

5. Reported TB Case Rates in Malawi 1988-2001
WHO TB Surveillance Report, 2003

6. DOTS and HIV-Related TB
DOTS is a critically important strategy for effective management of TB
DOTS increases cure rates, reduces mortality and prevents emergence of drug resistance
In the setting of HIV prevalence, DOTS alone is not sufficient to control TB incidence

7. C R E A E A brief history Autumn 2001 – concept sheet submitted
June 2002 – pilot grant for $3 million
September 2002 – Annecy meeting
February 2003 – proposals reviewed
June 2003 – London meeting on case finding
August 2003 – Seattle meeting with BMGF
November 2003 – 2nd Seattle meeting
January 2004 – final proposal submitted

8. End of the CREATE Meeting at the Bill and Melinda Gates Foundation, November 2003

9. Gates Foundation Press Briefing on TB and HIV at the Bangkok AIDS Conference July 15, 2004

10. C R E A E
Mission
To organize, implement and evaluate novel public health strategies to reduce tuberculosis incidence in populations with high rates of HIV and TB co-infection.

11. CREATE Objectives
Design, implement and evaluate a portfolio of community-level trials of new strategies designed to reduce TB incidence in communities with high HIV prevalence.
Transform global policies for HIV-related TB through evidence-based advocacy.

12. Strategies to Reduce TB/HIV in Addition to DOTS
Active or intensified case finding
to identify cases transmitting infection, and who may die without treatment
Treatment of latent TB infection
to prevent disease in HIV+ (and HIV-) persons
Household HIV/TB interventions linked to cases
to promote active case finding, identify candidates for TB preventive therapy (and antiretroviral drugs), and reduce HIV transmission
Combined ARV and IPT treatment programs
to reduce probability of developing primary or reactivation TB

13. The CREATE Portfolio: Current Studies
Study Site
Intervention(s)
Design
SA Gold Mines
Thibelo TB
Mass preventive therapy
Cluster randomized trial
Zambia/South Africa
ZAMSTAR
HH interventions, intensified case finding
Community randomized trial
Rio de Janeiro
Preventive therapy and ARVs
Phased implementation trial

14. Thibelo TB – Preventing TB
Gavin Churchyard, AURUM Health, South Africa

15. Mass Preventive Therapy with INH in South African Gold Miners
Design: Cluster randomized trial
Setting: 24 mine shafts with workers
Intervention: INH for all vs. standard of care (VCT with INH for HIV+, silicotics)
Endpoint: TB incidence and prevalence after 5 years

16. ZAMSTAR – Zambia and South Africa Tuberculosis and AIDS reduction trial
Helen Ayles – ZAMBART Project, Lusaka; Nulda Beyers – Stellenbosch University, South Africa
University of Zambia and Central Board of Health, Zambia
City of Cape Town and Provincial Department of Health, South Africa
London School of Hygiene and Tropical Medicine

17. ZAMSTAR Study Design 4-arm Community Randomised Trial Control
Improved standard of care
Enhanced Tuberculosis Case Finding (ECF)
Community level intervention (schools, market-places, open access diagnosis)
Household level TB and HIV combined activities (HH)
Household counselling intervention
Both ECF and HH
24 communities (16 in Zambia, 8 in Western Cape)
Primary endpoint: prevalence of culture proven tuberculosis after 4 years.

18. Study embedded in district health system
Control Communities will have
DOTS strengthening
TB/HIV Combined Activities (ProTEST)
Reporting to Study and National TB Control
All study communities will have enhanced monitoring and evaluation using standard indicators (TB; HIV; TB/HIV) and targets by evaluation team.
All interventions will be conducted by study staff embedded in the district health system working as additional TB/HIV coordinators

19. Cluster-randomized Trial of INH Preventive Therapy in HIV Clinics in Rio de Janeiro Betina Durovni, Rio City Health Department
Intervention:
Implementation of a comprehensive policy of screening for and treating latent TB in all HIV-infected patients
TST and INH PT for all TST+
Incentives/enablers to promote adherence
One clinic phased-in each month until ALL clinics are receiving intervention

20. Methods – Study Design Control group:
Clinic populations that have not yet been phased-in to begin implementation
Outcome – TB incidence over 3 years 29 4
Control
Clinic 3
Follow-up 2
Intervention 1
Month

21. With HIV (10%) An Epidemic --_-_--_-
ZAMSTAR > Thibelo TB and Brazil
ZAMSTAR
1.1 Infectious cases
18 HIV-ve
2 HIV+ve
1.8 cases
20 contacts
Goldmines> ZAMSTAR and Brazil
0.8
cases
An Epidemic
1.5 Non-Infectious

22. Stigma of HIV and TB CREATE Research portfolio
All IPT involves some targeted case finding
Mass ACF
Mass IPT
Symptomatic ACF
Thibelo TB
CREATE
Research portfolio
Targeted ACF
ZAMSTAR - Household
Community IPT
Community ECF
ZAMSTAR - ECF
Brazil
Health centre ECF
Stigma of HIV and TB
Clinic based IPT
DOTS- passive CF
Spectrum of Case Finding for TB
Spectrum of TB prevention

23. Existing TB and HIV policy and practice
Education and Training core
Existing TB and HIV policy and practice
Reduction in tuberculosis through transformed policies
Biostatistics core
New Knowledge
Mass ACF
Symptomatic ACF
Targeted ACF
Community ECF
Health centre ECF
DOTS- passive CF
Community IPT
Clinic based IPT
Mass IPT
CREATE
Research portfolio
Stigma
Policy and Advocacy core
Administration core

24. Executive Committee Richard Chaisson, Chair and PI (JHU)
Betina Durovni (SMS, Rio)
Peter Godfrey-Faussett (LSHTM)
Gavin Churchyard (Aurum Health Research)
Larry Moulton (JHU)
Paul Nunn (WHO)
Peter Small (BMGF)*
* Ex-Officio