Tuberculosis screening improves preventive therapy uptake (TB SCRIPT) trial among people living with HIV in Uganda: a study protocol of an individual randomized controlled trial

Fred C Semitala, Lelia H Chaisson, David W Dowdy, Derek T Armstrong, Bishop Opira, Kyomugisha Aman, Moses Kamya, Patrick P J Phillips, Christina Yoon, Fred C Semitala, Lelia H Chaisson, David W Dowdy, Derek T Armstrong, Bishop Opira, Kyomugisha Aman, Moses Kamya, Patrick P J Phillips, Christina Yoon

Abstract

Background: People living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear.

Methods: TB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice).

Discussion: This study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines.

Trial registration: ClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

Keywords: C-reactive protein; HIV; Randomized controlled trial; Screening; Tuberculosis; Tuberculosis preventive therapy.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study enrollment and baseline TB screening. Legend: (+) test-positive; (-) test-negative. Urine LAM-positive participants with risk factors for drug-resistant TB (prior TB treatment, contact with drug-resistant TB case) will undergo sputum Xpert Ultra testing for rapid detection of rifampin-resistance. All participants who test positive for TB (including urine LAM-positive/sputum Xpert Ultra-negative participants) will be referred to routine clinicians for TB treatment initiation

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