Evaluating Accuracy, Impact, and Operational Challenges of GeneXpert Use for TB Case Finding Among HIV-infected Persons

Summary

Background: In Botswana, as in the rest of sub-Saharan Africa, undiagnosed TB or TB diagnosed late in the course of disease is thought to be the most common cause of death among HIV-infected persons.

Interventions for Evaluation: The Xpert MTB/RIF assay for the GeneXpert platform (Xpert) has a TB diagnostic sensitivity of 82.4%, significantly superior to that of smear microscopy (44.6%). In line with WHO guidelines, the Botswana Ministry of Health (MOH) and CDC rapidly rolled out the Xpert device and a new Xpert-based diagnostic algorithm in service of 22 HIV care and treatment clinics. To maximize impact of the Xpert device in improving detection of active TB, Xpert rollout was preceded by strengthening of TB screening procedures by: (1) adopting the WHO-recommended 4-symptom TB screen for adults; (2) situating trained TB case-finding nurses in facilities; and (3) training health facility personnel in TB diagnostic algorithms. The combination of these strengthened TB screening procedures and rollout of the Xpert device is referred to as the "Xpert package" in this protocol.

Key Evaluation Objectives: The protocol has two key objectives: (1) to evaluate whether the new MOH-recommended Xpert-based TB diagnostic algorithm for new adult HIV clinic enrollees is more sensitive than the pre-Xpert smear-microscopy-based algorithm in diagnosing culture-positive TB disease; and (2) to evaluate the impact of the whole "Xpert package" on all-cause mortality during the first 6 months of ART, among adult patients.

Design: Stepped-wedge cluster randomized trial. Sample Size: 6,136 patients were prospectively enrolled to meet the first primary objective. A retrospective cohort of 10,131 persons was also enrolled to meet the second objective. Projected power to meet both objectives is \>80%.

Time line: Prospective cohort enrollment started in July 2012 and was complete by March 2014. Retrospective cohort enrollment was complete by March 2015. Patient follow-up and data entry will be complete in March 2016 at which time analysis to answer the first two primary study questions will be possible.

Conditions

• Tuberculosis
• Human Immunodeficiency Virus

Interventions

DEVICE

Xpert device

Interventions in the "Experimental phase" of this stepped-wedge trial include: (a) ensuring WHO-recommended TB screening adopted, (b) situating trained TB case finding nurses in the clinics, (c) training clinic personnel in the TB diagnostic algorithms, and (d) activation of the Xpert diagnostic device.

OTHER

Intensified TB Case Finding (ICF)

Interventions in the active comparator phase of this stepped wedge trial only include: (a) adoption of the WHO-recommended 4-symptom TB screen for adults; (b) situating trained TB case-finding nurses in the 22 facilities; and (c) training health facility personnel in TB diagnostic algorithms. There is no Xpert device activation in this phase. Only the standard of care microscopy algorithm (smear microscopy and chest x-ray) are available during this phase.

Sponsors & Collaborators

• Botswana Ministry of Health

  collaborator OTHER_GOV

• University of Pennsylvania

  collaborator OTHER

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Alyssa Finlay, MD · CDC Botswana

• Tedd V Ellerbrock, MD · CDC Atlanta

• Andrew F Auld, MBChB, MSc · CDC Atlanta

• Tefera Agizew, MD, MPhil · CDC Botswana

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

CROSSOVER

Eligibility

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-08-01

Primary Completion

2017-07-01

Completion

2017-07-01

Countries

• Botswana