Targeted Universal TB Testing With Simultaneous TPT Prescribing Among People Living With HIV in South Africa

Summary

Background: In 2023, the South African Department of Health introduced targeted universal TB testing (TUTT) at antiretroviral therapy (ART) initiation (irrespective of the presence of TB symptoms). Guidelines regarding TPT initiation in the setting of TUTT are conflicting - recommending either (1) delaying TPT initiation for all patients until a negative TB test result is returned2 or (2) delaying TPT only for those patients with a positive TB symptom screen. The new TUTT approach along with ambiguity in the timing of TPT initiation has the potential to substantially reduce timely TPT initiation - missing the period of highest TB risk. In modelling approaches for TB screening and TPT delivery, the investigators found that waiting for a sputum result could decrease TPT prescribing from the current level to approximately 17-31%.4 A novel alternative is to provide TPT at the time of TB testing to all patients initiating or re-initiating ART (TUTT-PT). Those who test positive for TB (5-8% of patients) would be promptly contacted and switched to anti-TB treatment. The investigators model suggests that this strategy could ensure that almost 90% of patients receive TPT and are tested for TB simultaneously. The viability of such an approach depends on demonstrating the safety and effectiveness of TPT for all vs the standard of care. Guiding the optimal implementation strategy for TPT delivery - balancing high-levels of TPT prescribing with rapid diagnosis and treatment initiation for active TB disease - is essential to ensure the continued success of South Africa's TPT program.

The investigators are conducting a one-year study built onto Fedisa PreventTB to compare the proposed novel approach of universal TPT to the standard approaches to inform further TPT policy and optimize the effectiveness of the Fedisa PreventTB behavioral economics approach in light of the new TB testing approach.

The overall aim is to pilot test the effectiveness and safety of targeted universal TB testing with simultaneous TPT (TUTT-PT) to increase TPT initiation among PLHIV initiating (or re-initiating) ART and to characterize clinic level implementation determinants among health care workers.

Conditions

• HIV/AIDS
• Tuberculosis

Interventions

OTHER

TUTT-PT Intervention

All TUTT-PT arm participants who provide written informed consent will have sputum collected for TB testing (if sputum was not already collected by the clinic staff) and will receive a clinical evaluation for the presence of TB symptoms (cough, fever, weight loss, night sweats) and serious contraindications for TPT initiation (known liver disease, high alcohol intake (men: \>5 drinks/day or \>15 drinks/week; women: \>4 drinks/day or \>8 drinks/week), or strong clinical suspicion of TB disease as evidenced by severity of symptoms, including haemoptysis, or Karnofsky score ≤50. PLHIV for whom the study nurse does not have a strong clinical suspicion of TB nor evidence of serious TPT contraindications will be referred to clinic staff for TPT initiation, irrespective of the presence or absence of TB symptoms.

Sponsors & Collaborators

• University of Witwatersrand, South Africa

  collaborator OTHER

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Christopher Hoffmann, MD, MPH · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-05-28

Primary Completion

2025-06-19

Completion

2025-06-19

Countries

• South Africa

Study Locations