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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV; Latent Tuberculosis
• Intervention / Treatment: Device: QGIT

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.

• Study Type: Interventional
• Enrollment (Actual): 3506
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Africa
  • North West
    • Klerksdorp, North West, South Africa
      • Tshepong Wellness Clinic
    • Klerksdorp, North West, South Africa
      • Bothabelo CHC
    • Klerksdorp, North West, South Africa
      • Grace Mokhomo
    • Klerksdorp, North West, South Africa
      • Jouberton
    • Klerksdorp, North West, South Africa
      • Marcus Zenzile
    • Klerksdorp, North West, South Africa
      • NM Pretorious Gateway
    • Klerksdorp, North West, South Africa
      • Orkney
    • Klerksdorp, North West, South Africa
      • Park Street
    • Klerksdorp, North West, South Africa
      • Stilfontein
    • Klerksdorp, North West, South Africa
      • Tsholofelo
    • Potchefstroom, North West, South Africa
      • Boiki Tihapi
    • Potchefstroom, North West, South Africa
      • Potchefstroom Gateway
    • Potchefstroom, North West, South Africa
      • Potchefstroom
    • Potchefstroom, North West, South Africa
      • Steve Tshwete

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: TST only; 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; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Witwatersrand, South Africa

Publications and helpful links

General Publications

• Kerrigan D, Tudor C, Motlhaoleng K, Lebina L, Qomfu C, Variava E, Chon S, Martinson N, Golub JE. Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial. BMC Health Serv Res. 2018 Apr 16;18(1):288. doi: 10.1186/s12913-018-3088-8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2014
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): May 1, 2019

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 18, 2014
• First Posted (ESTIMATE): April 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 3, 2019
• Last Update Submitted That Met QC Criteria: October 2, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: cost effectiveness; interferon-gamma; tuberculin test; cluster randomized trial; operational comparison; qualitative evaluation
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis; Latent Tuberculosis
• Other Study ID Numbers: NA_00085133; R01AI095041 (NIH)