Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Daria N Podlekareva,Igor Karpov,Dorte Bek Folkvardsen,Ole Kirk,Jens D Lundgren,Aliaksandr Skrahin,Troels Lillebaek,Henadz Hurevich,Dzmitry Klimuk,Alena Skrahina,Anna Vassilenko,Karl Drlica

doi:10.1155/2021/6646239

Abstract

Background To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome. Methods Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied. Results Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up. Conclusions We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients' outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

Highlights

Tuberculosis (TB) continues to be a major public health threat, especially due to drug-resistant TB (DR-TB) [1]
We explored the management of TB/HIV patients by comparing drug-susceptibility testing (DST) results from the Republican Scientific and Practical Center for Pulmonology and TB, Minsk, Belarus (Minsk), and the WHO TB Supranational Reference Laboratory (Copenhagen) in Copenhagen, Denmark
Even though the majority of patients were diagnosed with HIV infection several years before TB diagnosis, only a small proportion were on antiretroviral therapy (ART) at time of TB diagnosis, and the majority had low CD4 cell counts (Table 2)

Summary

Introduction

Tuberculosis (TB) continues to be a major public health threat, especially due to drug-resistant TB (DR-TB) [1]. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Designed individualized treatment regimens in accordance with DST patterns will likely improve patients’ outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains

Methods

Results

Conclusion