Pulmonary tuberculosis screening in anti-retroviral treated adults living with HIV in Kenya

Jill K Gersh,Daniel Matemo,Zachary Feldman,Maureen Kamene,Alex J Warr,Sylvia M Lacourse,Ruanne V Barnabas,John Kinuthia,Jerphason Mecha,David J Horne

doi:10.1186/s12879-021-05916-z

Abstract

BackgroundPeople living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed.MethodsWe enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis.ResultsThe study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8–1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4–3.0%): 4.3% (0.5–14.5%) among IPT-naïve and 0.9% (0.2–2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0–52%) and specificity 87% (83–90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28–100) and specificity 72% (67–77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31–2.23).ConclusionsIn Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.

Highlights

Tuberculosis (TB) remains the leading cause of death in people living with Human immunodeficiency virus (HIV) (PLHIV)
We evaluated the accuracy of the World Health Organization (WHO) intensified case finding (ICF) screen for TB and investigated the performance of candidate biomarkers as TB triage tests in People living with HIV (PLHIV) who were overwhelmingly receiving antiretroviral therapy (ART)
Between March 2017 and June 2018, 390 PLHIV were screened for study eligibility, among whom two declined study entry, two did not have sputum collected, and three had contaminated sputum cultures

Summary

Introduction

Tuberculosis (TB) remains the leading cause of death in people living with HIV (PLHIV). Isoniazid preventive therapy (IPT) administered for 6 months is a World Health Organization (WHO) recommended regimen that remains the most widely used TB preventive therapy [3]. In moderate and high TB burden areas, re-infection with M. tuberculosis due to frequent re-exposure may limit the durability of TB preventive therapy’s protective benefit. This was observed in the initial trials of IPT in PLHIV [4,5,6], in which TB rates significantly increased approximately 6 months after completing treatment. People living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving antiretroviral therapy is sub-optimal and alternative screening strategies are needed

Methods

Results

Conclusion