# The diagnostic value of Xpert detection combined with nanopore sequencing for tuberculosis in HIV/AIDS patients

## TL;DR

This study shows that combining nanopore sequencing with Xpert improves tuberculosis diagnosis in HIV/AIDS patients, offering better accuracy than individual methods.

## Contribution

The novel contribution is demonstrating that combining nanopore sequencing with Xpert enhances TB diagnostic performance in HIV/AIDS patients.

## Key findings

- Nanopore sequencing alone achieved 60.50% sensitivity and 90.50% specificity for TB diagnosis in HIV/AIDS patients.
- Combining nanopore sequencing with Xpert improved sensitivity to 71.10% and AUC to 0.78.
- The combination method showed a Kappa coefficient of 0.523, indicating moderate agreement beyond chance.

## Abstract

•Nanopore sequencing enhances TB diagnostic accuracy, achieving 60.50% sensitivity by detecting low pathogen loads and reducing missed cases.•Combining nanopore sequencing with other methods compensates for individual test limitations, improving overall diagnostic reliability.•Clinicians should integrate multiple factors, including clinical symptoms and immune status, to interpret nanopore sequencing results effectively.

Nanopore sequencing enhances TB diagnostic accuracy, achieving 60.50% sensitivity by detecting low pathogen loads and reducing missed cases.

Combining nanopore sequencing with other methods compensates for individual test limitations, improving overall diagnostic reliability.

Clinicians should integrate multiple factors, including clinical symptoms and immune status, to interpret nanopore sequencing results effectively.

Tuberculosis (TB) remains a major cause of death in HIV/AIDS patients, where diagnosis is complicated by atypical presentation and paucibacillary disease. Current diagnostic methods have limitations in speed or sensitivity. This study evaluates the diagnostic value of rapid, portable nanopore sequencing for TB in this high-risk population.

Clinical data and diagnostic results were collected from 59 HIV/AIDS patients with suspected tuberculosis. The diagnostic performance of nanopore sequencing was compared with AFB staining, TB-DNA testing, Xpert, and solid mycobacterial culture, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Kappa coefficient, and the area under the receiver operating characteristic curve (AUC). Additionally, this study further evaluated the diagnostic performance of nanopore sequencing in combination with AFB staining, TB-DNA testing, Xpert, and culture methods.

Nanopore sequencing showed the highest performance among all methods, with a sensitivity of 60.50%, specificity of 90.50%, PPV of 92.00%, NPV of 55.90%, and AUC of 0.76. When used in combination with other methods, nanopore sequencing and Xpert achieved the best diagnostic performance, with a sensitivity of 71.10%, specificity of 85.70%, PPV of 90.00%, NPV of 62.10%, Kappa value of 0.523, and an AUC of 0.78.

The combination of nanopore sequencing and Xpert demonstrates excellent diagnostic performance for diagnosing TB in HIV/AIDS patients.