TUTT-PT: Targeted Universal TB Testing With Simultaneous TPT Prescribing Among People Living With HIV in South Africa
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 364
- 试验地点
- 1
- 主要终点
- Participants Who Receive TPT Within 7 Days of ART Initiation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Person living with HIV stable on ART
- •Not speaking any of the languages spoken by the study team
研究组 & 干预措施
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.
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.
干预措施: TUTT-PT Intervention (Other)
结局指标
主要结局
Participants Who Receive TPT Within 7 Days of ART Initiation
时间窗: Within 7 days of ART initiation
Between-arm comparison of the proportion of PLHIV initiating TPT ≤7 days after ART initiation.
Participants Initiated TPT ≤ 7 Days of ART Initiation With Positive TB Test
时间窗: 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.
Time (Days) to TB Treatment Initiation
时间窗: 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.
Participants With Positive TB Test
时间窗: Up to 90 days post-ART initiation
Between-arm comparison of the proportion of PLHIV with a positive TB test result.
次要结局
未报告次要终点