Analysis of microorganisms and drug-resistance mutations detected by probe-capture metagenomics among HIV-infected patients with pneumonia

<h4>Background</h4>Probe-Capture Metagenomics is a newly developed method for detecting infectious pathogens. However, its application in HIV-infected patients with pulmonary infection remains limited. This study utilized Probe-Capture Metagenomics to analyze lung microbiomes and Drug Resistance Mutations of HIV and bacteria in people living with HIV (PLWH) with pneumonia.<h4>Methods</h4>We retrospectively investigated lung microorganisms in PLWH hospitalized at Zhongnan Hospital of Wuhan University. A combination of bronchoalveolar lavage fluid Probe-Capture Metagenomics and conventional microbiological tests were performed in all patients.<h4>Results</h4>A total of 91 patients were included in the study. Excluding the EB and Torque teno virus, at least two organisms were identified in 85 patients using Probe-Capture Metagenomics combined with conventional microbiological tests. The top six detected organisms were CMV, <i>Pneumocystis jirovecii</i>, <i>Mycobacterium tuberculosis complex</i>, HHV-7, <i>Candida albicans and Aspergillus</i>. For specific organisms, the detection rate of CMV and <i>Candida albicans</i> by Probe-Capture Metagenomics was significantly higher than that of conventional microbiological tests (<i>p</i> < 0.0001). Moreover, the detection rates of CMV (<i>p</i> = 0.0167) and <i>Pneumocystis jirovecii</i> (<i>p</i> = 0.04) in patients with CD4⁺T count ≥ 200 cells/μL were higher than that with CD4⁺T count < 200 cells/μL. Importantly, Probe-Capture Metagenomics can uncover potentially clinically relevant drug-resistance mutations linked to HIV and bacteria.<h4>Conclusion</h4>Probe-Capture Metagenomics provides a promising method of detecting suspected opportunistic infections in PLWH with pneumonia, especially for mixed infections and rare microorganisms. In addition, Probe-Capture Metagenomics was a potential valuable tool for genotyping resistance testing of HIV and bacteria.