Targeted Universal TB Testing With Simultaneous TPT Prescribing Among People Living With HIV in South Africa (TUTT-PT)
TUTT-PT: Targeted Universal TB Testing With Simultaneous TPT Prescribing Among People Living With HIV in South Africa
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 returned 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%. 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background HIV and TB in South Africa. South Africa is home to over 7.5 million people living with HIV (PLHIV), more than any other country globally. In addition, South Africa has one of the highest incidence rates of tuberculosis (TB) worldwide, estimated at 513 cases per 100,000 individuals in 2021. In recent years, several studies in high TB-burden settings have evaluated the prevalence and clinical features of asymptomatic, or subclinical, TB using universal TB testing, irrespective of symptom status. In a 2021 review of TB prevalence surveys conducted in 23 countries across Africa and Asia, a median of 50. Four percent of TB disease identified in population-based surveys was identified as subclinical.15 Studies have also reported on the prevalence of subclinical TB among PLHIV in South Africa.
The new approach for universal TB testing is a paradigm shift for South Africa. In the 2023 ART Clinical Guidelines, the South African National Department of Health (NDoH) called for targeted universal TB testing (TUTT) for people living with HIV as a component of the clinical evaluation for ART and TPT initiation, irrespective of symptom status. However, guidelines regarding the timing of TPT initiation are conflicting - recommending either (1) delaying TPT initiation for all patients until a negative TB test result is returned 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%. A novel alternative is to provide TPT at the time of TB testing to all patients initiating or re-initiating ART (TUTT-PT).
There is a knowledge gap regarding the potential viability, safety, and effectiveness of TUTT-PT for PLHIV initiating ART. The investigator's model suggests that the TUTT-PT strategy of universal TB testing with universal TPT (and switch to anti-TB treatment for those who test positive for TB) could ensure that almost 90% of patients receive TPT and are tested for TB simultaneously. The viability of such an approach, however, depends on demonstrating the safety and effectiveness of TUTT-PT 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 Fedisa PreventTB study has a currently active platform to compare these two strategies to continue to optimize TPT delivery. The investigators will conduct a one-year study built into Fedisa PreventTB to compare the novel approach of TUTT-PT to the standard approach to inform further TPT policy and optimize the effectiveness of the Fedisa PreventTB behavioural economics approach to TPT prescribing.
Early identification and treatment of active TB disease is critical to reduce transmission of TB. However, universal TB testing for newly initiating or re-initiating ART clients may result in delayed and/or decreased TPT prescribing at a time of high TB risk for PLHIV. Universal TB testing combined with universal TPT prescribing would ensure simultaneously high rates of TB prevention, testing, diagnosis, and treatment initiation for this high-risk group.
Study design The investigators are proposing a non-randomized pilot evaluation of a universal TPT initiation strategy within the context of TUTT implementation for PLHIV initiating or re-initiating ART. Clinics will be assigned to the novel TUTT-PT arm or standard TUTT implementation arm with the primary analysis focused on the proportion initiated on TPT within 7 days of ART start. This study will also assess the rate of new TB diagnoses, TB treatment initiation for those testing positive for TB, the prevalence of TB drug resistance at the time of TB treatment initiation, time to TPT initiation, and provider experiences with TUTT implementation and TPT provision, among others.
Study setting This study will be conducted by Perinatal HIV Research Unit (PHRU) in 4 or more public sector health facilities in the Dr Kenneth Kaunda district, North West province, South Africa that are participating in the Fedisa PreventTB study. As of 2016, the Dr Kenneth Kaunda district has a population of 742,820 with HIV prevalence estimated as 12.9%.22 The Fedisa PreventTB study was conducted in 18 public-sector health facilities providing HIV and TB related care. Thus, the PHRU team is very familiar with the study setting and has strong relationships with the provincial Department of Health, the district and sub-district offices, and the clinic managers and staff.
A primary goal is to test the safety of universal TPT with TUTT. To maximize safety in terms of immediate receipt of appropriate anti-TB therapy, each clinic, irrespective of arm, will be supported by a PHRU study team tracer. Any participant who tests positive for TB will be immediately contacted by the tracer telephonically. Those who cannot be reached via telephone will be visited at the household by the tracer to alert the participant of the TB test result and facilitate return to the clinic for switch from TPT to anti-TB treatment (or to initiate anti-TB treatment if not on TPT). All participants who test positive for TB will have two additional spot sputum specimens collected on the date of anti-TB treatment initiation. The first specimen will be used as per routine care. The second specimen will be sent for study-specific culture and drug-susceptibility testing.
Participants who test positive for TB will be referred to clinic staff for termination of TPT and initiation of anti-TB treatment. Those with trace results on Xpert Ultra will be managed as per routine care. No further interaction between the study nurse and the participant will take place thereafter.
The investigators hypothesize that TPT prescribing will be 65% in routine TUTT implementation and 80% in TUTT-PT implementation. Thus, the investigators will enroll 200 PLHIV in TUTT clinics and 200 PLHIV in clinics where the participants will receive TUTT-PT (400 total) in order to detect this difference with 80% power at a 5% level of significance while accounting for clustering by clinic (a design effect of approximately 1.3). A sample size of 400 will also enable the investigators to identify an estimated 20 new ART clients diagnosed with TB (assuming prevalence of 5%) in order to evaluate time to TB treatment initiation. In addition, throughout study implementation, the investigators will conduct ongoing monitoring of intervention safety, defined as the number of participants diagnosed with TB who remain on TPT after diagnosis by study arm.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Gauteng
-
Soweto, Gauteng, South Africa, 1864
- Perinatal HIV Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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 telephonically or via a home visit by a study team tracer
- Willing and able to provide written informed consent
Exclusion Criteria:
- Person living with HIV stable on ART
- Not speaking any of the languages spoken by the study team
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
No Intervention: No Intervention: Standard of care study arm
In the standard TUTT implementation arm, ART clients who initiated or re-initiated ART will be referred to the study nurse for eligibility screening, enrollment, 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.
|
|
|
Experimental: TUTT-PT Intervention
In the TUTT-PT arm, newly initiating or re-initiating ART clients will be referred by the clinic nurse after ART initiation to the study nurse for eligibility screening and enrollment.
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Participants Who Receive TPT Within 7 Days of ART Initiation
Time Frame: Within 7 days of ART initiation
|
Between-arm comparison of the proportion of PLHIV initiating TPT ≤7 days after ART initiation.
|
Within 7 days of ART initiation
|
|
Participants Initiated TPT ≤ 7 Days of ART Initiation With Positive TB Test
Time Frame: Up to 90 days post-ART initiation
|
Between-arm comparison of the proportion of PLHIV initiating TPT ≤7 days after ART initiation and have a subsequent positive TB test result.
|
Up to 90 days post-ART initiation
|
|
Time (Days) to TB Treatment Initiation
Time Frame: Up to 90 days post-ART initiation
|
Safety evaluation 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
|
|
Participants With Positive TB Test
Time Frame: Up to 90 days post-ART initiation
|
Between-arm comparison of the proportion of PLHIV with a positive TB test result.
|
Up to 90 days post-ART initiation
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Christopher Hoffmann, MD, MPH, Johns Hopkins University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Blood-Borne Infections
- Urogenital Diseases
- Genital Diseases
- Immune System Diseases
- Infections
- RNA Virus Infections
- Virus Diseases
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Slow Virus Diseases
- Gram-Positive Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Actinomycetales Infections
- Mycobacterium Infections
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Tuberculosis
Other Study ID Numbers
- IRB00420733
- R01AI150432-03 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.