1. Impact of tuberculosis screening and isoniazid preventive therapy on incidence of TB and death in the TB/HIV in Rio de Janeiro (THRio) study
B. Durovni1,2, V. Saraceni1, A. Pacheco3, S. Cavalcante1,3, S. Cohn4, B. King4, L. Moulton4, R. Chaisson4, J. Golub4, THRio study group
1Rio de Janeiro City Health Secretariat, Rio de Janeiro, Brazil,
2Federal University of Rio de Janeiro, Rio de Janeiro, Brazil,
3Fiocruz, Rio de Janeiro, Brazil,
4Johns Hopkins University, Baltimore, United States

2. THRio Objectives
To determine if implementation of a policy of widespread use of isoniazid preventive therapy (IPT) in HIV-infected patients with access to ARV therapy reduces the incidence of active TB and death in the HIV clinic population
Scale up of tuberculin skin testing (TST) and IPT among HIV-infected patients in public primary health units in Rio de Janeiro within the current HIV clinic infrastructure
In an effort to reduce:
TB Incidence
Mortality

3. Setting
29 Public Health units managed by the Health Department of Rio de Janeiro City
AP5.3
AP5.2
AP4
AP5.1
AP3.3
AP3.2
AP1
AP3.1
AP 2.1
AP2.2 3

4. THRio Study Design and Timeline Cluster-Randomized, Step-Wedge Trial
Sep 05
Jan 08
48 60
Aug 09
Intervention and
Follow-up Period
(for all clinics) 4

5. Intervention
Training clinics to properly implement TB screening and adhere to TST/IPT policy for all HIV-infected patients
TST to be done for all eligible
clinic patients
No prior TB history
No prior IPT
No prior +TST
IPT x 6 months for all TST+ without active TB and all contacts of active TB cases 5

6. TST and IPT 69% had at least one TST placed and read 83% started IPT
0.84% had an adverse event
84% completed IPT

7. Time to TST and Time to IPT Before and After THRio Intervention
Time to TST and time to IPT are both markedly improved post-intervention
Durovni et al., AIDS 2010, 24 (suppl 5):S49–S56

8. Methods for Current Analysis
Primary endpoints: Incidence of TB and TB or death at the clinic level before and after the intervention
Eligible patients who made > 1 visit after 1 Sept 2003
‘Eligible’ = no prior TB or IPT
‘Prevalent’ TB and deaths (within 60 days of enrollment) excluded
Patients remain in the denominator until TB or Death
Intent-to-treat Analysis – includes all eligibles
“Stayers” Analysis -- among those remaining in clinic contact, censoring those missing for >1 year (mITT)
Statistical analysis: Crude hazard ratios (HR) obtained from frailty-adjusted
Cox models are presented

9. CONSORT Diagram (modified for stepped wedge cluster-randomized trial)
Clinics Eligible for Inclusion (n=29)
Clinics Receiving Intervention (n=29)
Patients in Clinics Eligible for Intervention (n=12,815)
Eligible patients contributing to control phase (n=9,853 )
Eligible patients contributing to intervention phase (n= 10,840)
Patients in Clinics Ineligible for Intervention (n=4,480)

10. THRio cohort characteristics (n=12,815)
Median age: 37 years old
Male: 61%
Median years since HIV diagnosis: 2.4 years
HAART at entry: 60%
Median CD4 cell count at entry: 403 cells/mm3

11. Incidence of TB Over Time
X: start of intervention | : control case | : intervention case

12. THRio Results TB cases, total contribution time, incidence per 100pyrs
Control Phase Intervention Phase
Cases
Person years , ,126
Rate/100pyrs
TB/Death cases, total contribution time, incidence per 100pyrs
Control Phase Intervention Phase
Cases
Person years , ,126
Rate/100pyrs

13. THRio Results: Unadjusted Cox Models
Outcome
Cases
HR (95% CI)
p-value
Intent To
Treat TB
475
0.87
( )
0.233
TB or Death
1313
0.72
( )
<0.001
Intent-to-treat – Among all eligibles

14. THRio Results: Unadjusted Cox Models
Outcome
Cases
HR (95% CI)
p-value
Intent To
Treat TB
475
0.87
( )
0.233
TB or Death
1313
0.72
( )
<0.001
Modified
To Treat
(Stayers)
403
0.57
( )
TB or Death
1073
0.56
( )
Intent-to-treat – Among all eligibles
Stayers – mITT - Among those remaining in clinic contact
(Patients censored at the moment they go one year without a clinic contact)

15. Conclusions
Overall, the THRio intervention had a modest impact (13% reduction) on TB, but showed an important and statistically significant impact on TB and death (28% reduction) in the primary intent-to-treat analysis;
The “Stayers” analysis, including those who were more likely to be exposed to the intervention (mITT), showed an even larger and highly significant impact on reduction of TB incidence (43%) and TB incidence and death (44%)
TST screening and provision of IPT to HIV-infected patients with access to highly active antiretroviral therapy significantly reduces the risk of TB and death and should be widely implemented

16. THRio Study Team Rio de Janeiro Betina Durovni Solange Cavalcante
Valeria Saraceni
Antonio Pacheco
Giselle Israel
Vitoria Vellozo
Rita Ferreira
Lilian Lauria
THRio Study Team
JHU
Richard Chaisson
Jonathan Golub
Larry Moulton
Silvia Cohn
Bonnie King
Anne Efron
Susan Dorman
THRio Study Team
Funding: Bill and Melinda Gates Foundation