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

NCT06739915 | Completed

• 1 other identifier: IRB00420733
• Study Type: interventional
• Target: 414
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Tuberculosis Preventive Therapy

Outcome Measures

Primary Outcomes (3)

• Proportion of Participants Who Receive TPT

  To compare the proportion of PLHIV who initiate TPT within 7 days of ART initiation based on same day TPT or not.

  Within 7 days of ART initiation

• Participants with Positive TB test

  To compare the proportion of PLHIV who initiate TPT and have a subsequent positive TB test result based on same day TPT or not.

  Up to 90 days post-ART initiation

• Time (days) to TB treatment initiation

  To estimate the safety of each TPT initiation approach based on the median time to TB treatment initiation among those who test positive for TB based on same day TPT or not.

  Up to 90 days post-ART initiation

Study Arms (2)

No Intervention: Standard of care study arm

NO INTERVENTION

In the standard TUTT implementation arm, ART clients who initiated or re-initiated ART will be referred to the PHRU study nurse for eligibility screening, enrolment, and a clinical evaluation after the consultation has been completed. All laboratory investigations and ART and TPT prescribing will occur as per routine care in the facility prior to referral to the PHRU study nurse who will obtain written informed consent for study participation.

TUTT-PT Intervention

EXPERIMENTAL

In the TUTT-PT arm, newly initiating or re-initiating ART clients will be referred by clinic staff after ART initiation to the PHRU study nurse for eligibility screening and enrolment. 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.

Other: TUTT-PT Intervention

Interventions

TUTT-PT Intervention OTHER

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.

TUTT-PT Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years and older
• Person living with HIV newly initiating or re-initiating ART at a participating site.
• Residing within the catchment area of the clinic and willing to be followed up at telephonically or via a home visit by a study team tracer.
• Willing and able to provide written informed consent.

You may not qualify if:

• Person living with HIV stable on ART.
• Not speaking any of the languages spoken by the study team

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of Witwatersrand, South Africa: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Perinatal HIV Research Unit

Soweto, Gauteng, 1864, South Africa

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Christopher Hoffmann, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The data identified by clinic allocation will be blinded to the PI and co-investigators and study statistician until completion of comparative analysis. There will be no other blinding.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 18, 2024
• Study Start: May 28, 2024
• Primary Completion: June 19, 2025
• Study Completion: June 19, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: One year after completion of study activities
• Access Criteria: Contact PI

Locations

ZA (1)