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thrio

THRio Study

A Clinic-Randomized Trial of INH Preventive Therapy in HIV+ Patients

The Study

THRio was a study designed to evaluate the implementation of tuberculin skin tests (TST) and isoniazid preventive therapy for HIV-patients living in Rio de Janeiro. THRIo was designed to determine the impact of an intervention to increase use of isoniazid preventive therapy (IPT) and the subsequent effect on rates of TB and death in HIV-infected patients living in Brazil, where antiretroviral therapy is widely used.

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The Outcome

The THRio intervention demonstrated increased uptake of existing TB policies for patients treated in HIV clinics, and a reduction in TB and death following the intervention.

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The Conclusion

IPT is additive to ART and the intervention reduced TB and death for people living with HIV. Thus scale-up of IPT for HIV-infected patients in moderate TB incidence settings is achievable and should be strongly considered in Brazil and similar settings.

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The Study

The TB/HIV no Rio study (THRio) was a phased implementation study of tuberculin skin testing (TST) and isoniazid preventive therapy (IPT) in 29 HIV clinics in Rio de Janeiro, Brazil. The primary activity of the intervention was the training and education of HIV clinic personnel to implement Brazil’s TB prevention guidelines, which had been poorly adhered to prior to THRio. Every two months starting in September 2005, HIV and TB staff at two clinics were trained, and thus phased into the intervention period of the study, until all clinics had received the training. TB and mortality outcomes were compared between the intervention period of follow-up and the control period (period in each clinic prior to the intervention training).

The primary objective was to compare TB disease between intervention and control periods, and the secondary objective was to compare TB disease and/or mortality between periods.

INTERVENTION

The Outcome

THRIO PRIMARY RESULTS INTENT-TO-TREAT

TB cases TB/Death
Control Intervention Control Intervention
Cases/Events 221 254 612 701
Person-Years 16830 23093 16830 23093
Incidence Rate
(per 100 PYs)
1.31 1.01 3.64 3.04
Crude
Hazard Ratio
(95% CI)
0.87
(0.69-1.10)
p = 0.24
0.76
(0.66-0.87)
p < 0.001
Adjusted
Hazard Ratio*
(95% CI)
0.73
(0.54-0.99)
p = 0.04
0.69
(0.57-0.83)
p < 0.001

THRIO PRIMARY RESULTS STAYERS ANALYSIS

TB cases TB/Death
Control Intervention Control Intervention
Cases/Events 200 199 502 553
Person-Years 11307 18008 11307 18008
Incidence Rate
(per 100 PYs)
1.77 1.11 4.44 3.07
Crude
Hazard Ratio
(95% CI)
0.42
(0.31-0.58)
p < 0.001
0.50
(0.41-0.60)
p < 0.001
Adjusted
Hazard Ratio*
(95% CI)
0.42
(0.29-0.60)
p < 0.001
0.45
(0.35-0.56)
p < 0.001

LIMITATIONS OF THRIO INTERVENTION

Newly Diagnosed HIV

10% of newly diagnosed HIV-patients presented with TB, thus were unable to benefit from the intervention

  • Need for earlier HIV diagnosis

 

TST and IPT

Though median time toTST and IPT were markedly reduced post-intervention, 36% of TB cases diagnosed post-intervention had not yet received a TST, and were therefore not eligible for IPT

  • TST is a limiting factor
  • IPT should be considered for all HIV-positives
  • There is a need to better operationalize provision of TST and IPT

 

Reduction of Impact

Our intention-to-treat analysis included all patients active in the clinics prior to THRio start; however, many never attended the clinic during the intervention period, thus reducing impact

  • Our secondary analyses of “stayers”, focusing on patients who were retained in clinic care, reported 50% impact on TB and mortality
  • Emphasizes need to keep patients in care

TST Uptake

Intervention increased TST uptake and shortened time to both TST and IPT

IPT

IPT worked extremely well at individual level and was additive to ART

Reduced TB

Intervention reduced TB and TB/death significantly in adjusted ITT analysis, and markedly when analysis was restricted to patients who were retained in care