Quantiferon Gold Test for Detecting Tuberculosis (TB) Infection in HIV/AIDS Patients in South Africa

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to use a cluster randomized trial to compare the effectiveness of linking the Quantiferon-gold in-tube test (QGIT) with routine CD4 testing to the routine use of the tuberculin skin test (TST), the current standard of care for diagnosing latent tuberculosis infection (LTBI) in South Africa. The investigators hypothesize that QGIT clinics will identify LTBI and initiate isoniazid preventive therapy (IPT) in a higher proportion of patients and in a significantly faster timeframe. The cost-effectiveness of linking QGIT with routine CD4 compared to routine TST will also be evaluated, and the process of implementation of QGIT into the routine cluster of differentiation 4 (CD4) blood draw will be evaluated using a mixed method approach to identify steps that can be modified for future scale-up of the intervention.

Detailed Description
-----------------
The investigators propose a cluster randomized trial in 16 HIV clinics in South Africa to compare time to determine LTBI status in patients in clinics using QGIT and TST and those with TST only. The investigators will take advantage of the excellent HIV services provided in South Africa and link QGIT with CD4 blood collection and provide the first evidence of an operational comparison between QGIT and TST in HIV-infected patients in a country that accounts for one-third of the HIV-related TB in the world. The QGIT study will contribute to the understanding of QGIT performance and implementation in HIV-infected individuals. Careful evaluation of the implementation and operational aspects of the program will provide useful knowledge for future scale-up in this and other HIV clinic settings.

Official Title
-----------------
Quantiferon Gold Test for Detecting TB Infection in HIV/AIDS Patients in South Africa

Conditions
-----------------
Latent Tuberculosis, HIV

Intervention / Treatment
-----------------
* Device: QGIT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV-infected >= 18 years of age attending one of the 14 clinics during the duration of the study eligible to receive TST or IPT according to South Africa guidelines Exclusion Criteria: diagnosed with active tuberculosis not eligible to receive TST or IPT according to South Africa guidelines

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: TST only<br>Tuberculin skin test for all eligible patients, to be placed and read by clinic staff. Thereafter, for 2 years, annual TST provided for patients with TST negative/unknown history. IPT to be provided to patients with a positive TST for whom active TB has been ruled out. | |
| Experimental: QGIT<br>QGIT for all eligible patients, to be done at routine CD4 blood draw. Thereafter, for 2 years, annual QGIT at CD4 blood draw for patients with QGIT negative/unknown history. IPT to be provided to patients with a positive QGIT for whom active TB has been ruled out. | Device: QGIT<br>* Seven pairs of clinics will be included in this study. One clinic in each pair will be selected by a computerized randomization program to be the standard of care arm (TST only) and the other will be in the QGIT arm.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of linking QGIT with CD4 blood collection and the current standard of care process of TST in HIV clinics in South Africa on operational metrics |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Time to known latent TB infection status in clinics integrating QGIT with CD4 blood draw versus clinics with current standard of care (TST only) |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Time to provision of IPT for eligible patients in QGIT versus TST-only clinics |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Proportion of patients with known LTBI status in QGIT and TST-only clinics |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Proportion of eligible patients receiving IPT between QGIT and TST-only clinics |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Proportion of eligible patients receiving a second TST or QGIT following an initial negative test |  | Participants will be followed for the duration of the study, an expected average of 2 years | 
| Patient-, provider-, and clinic-level factors that impact outcomes within and between arms |  | Participants will be followed for the duration of the study, an expected average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost effectiveness of implementing QGIT versus TST-only | Costs and effectiveness (quality-adjusted life years) of LTBI screening and treatment with QGIT versus TST standard of care. Looking at the impact on the HIV-associated TB epidemic in South Africa under each strategy and scenarios under which QGIT is cost-effective relative to TST, and vice versa. | 1 year | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of key clinic personnel | Knowledge, attitudes and practices of clinic personnel, along with consensus regarding key factors linked to successful screening | up to 6 months | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of patients | Patients' understandings and experiences with TB screening approaches, along with consensus regarding key factors linked to successful screening | up to 6 months | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of clinic personnel | Knowledge, attitudes and practices of clinic personnel, along with consensus regarding key factors linked to successful screening | 1 year | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of patients | Patients' understandings and experiences with TB screening approaches, along with consensus regarding key factors linked to successful screening | 1 year | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of clinic personnel | Knowledge, attitudes and practices of clinic personnel, along with consensus regarding key factors linked to successful screening | 2 years | 
| Attitudinal and operational factors influencing the successful implementation of QGIT versus TST diagnostic practices from the perspective of patients | Patients' understandings and experiences with TB screening approaches, along with consensus regarding key factors linked to successful screening | 2 years | 
| Cost effectiveness of implementing QGIT versus TST-only | Costs and effectiveness (quality-adjusted life years) of LTBI screening and treatment with QGIT versus TST standard of care. Looking at the impact on the HIV-associated TB epidemic in South Africa under each strategy and scenarios under which QGIT is cost-effective relative to TST, and vice versa. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cluster randomized trial, interferon-gamma, tuberculin test, operational comparison, cost effectiveness, qualitative evaluation