Abstract
<title>Abstract</title> <p>Background Pulmonary complications are leading causes of poor prognosis in people living with HIV (PLWH). Though antiretroviral therapy (ART) recovers systemic immunity, its effects on lung pathogens remain unclear. This retrospective research explored how ART shapes lung pathogen profiles and loads in PLWH complicated with pulmonary infection. Methods This retrospective study enrolled 62 PLWH with suspected pneumonia. Patients were categorized into ART (n = 29) and ART-naïve (n = 33) groups. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid was performed to profile bacterial, fungal, and viral communities. Microbial features, pathogen burden and clinical indicators were compared statistically. Results The ART group exhibited significantly higher CD4⁺ T cell counts (median 131 vs. 44 cells/µL, P = 0.0049) and suppressed HIV viral load (median 185 vs. 259,000 copies/mL, P < 0.0001). mNGS revealed a distinct shift in co-infection patterns: ART recipients showed more bacterial-viral co-infections, while ART-naïve patients had more fungal-viral co-infections. ART significantly reduced the total pathogen burden (mean 3.7 ± 2.0 vs. 5.0 ± 2.6, P < 0.05), primarily through the suppression of fungal (P < 0.05) and viral loads (P < 0.05), with no significant effect on bacterial counts. Clinically, the ART group had significantly better outcomes (93.1% vs. 72.7% improvement, P = 0.036) and a trend toward shorter hospital stays. Conclusion ART remodels the pulmonary microbial community in PLWH and lowers total pathogen burden through targeted suppression of opportunistic fungi and viruses. These findings underscore that ART plays a vital role in managing pulmonary co-infections, with therapeutic benefits extending well beyond systemic HIV viral suppression alone.</p>