Intestinal dysbiosis is common in people living with HIV/AIDS (PLWH), yet fungal communities of the gut microbiota (mycobiota) remain poorly characterized, especially in severely immunosuppressed patients. We analyzed the gut mycobiota of 33 PLWH and 20 healthy controls from a public hospital in central Argentina. Most PLWH presented severe immunosuppression (<200 CD4+ T cells/μL) and acute or chronic diarrhea, with or without antibiotic exposure or antiretroviral therapy. Fecal DNA was extracted and the ITS2 region was sequenced using next-generation sequencing. Beta-diversity analyses revealed significant segregation between PLWH and controls (PERMANOVA, Adonis: p = 0.001, R² = 0.0989). LEfSe analysis identified 17 fungal species enriched in PLWH, predominantly Candida albicans, Candida dubliniensis, and Nakaseomyces glabratus, whereas 31 species were more abundant in controls, including Penicillium spp., Candida sake, and Clavispora lusitaniae. Histoplasma capsulatum, an endemic pathogen in the region, was more prevalent in PLWH and associated with CD4+T-cell counts. Dirichlet multinomial mixture analysis revealed two mycobiotypes: M1, with a balanced fungal composition predominating in controls, and M2, dominated by Candida species and present in PLWH. These findings provide novel insights into gut mycobiota alterations in severely immunosuppressed PLWH in Argentina, highlighting Candida-driven dysbiosis and the regional relevance of H. capsulatum.

Intestinal dysbiosis is common in people living with HIV/AIDS (PLWH), yet fungal communities of the gut microbiota (mycobiota) remain poorly characterized, especially in severely immunosuppressed patients. We analyzed the gut mycobiota of 33 PLWH and 20 healthy controls from a public hospital in central Argentina. Most PLWH presented with severe immunosuppression (<200 CD4⁺ T cells/μL) and acute or chronic diarrhea, with or without antibiotic exposure or antiretroviral therapy. Fecal DNA was extracted and the ITS2 region was sequenced using next-generation sequencing. Beta-diversity analyses revealed significant segregation between PLWH and controls (PERMANOVA, Adonis: p = 0.001, R² = 0.0989). LEfSe analysis identified 17 fungal species enriched in PLWH, predominantly Candida albicans, Candida dubliniensis, and Nakaseomyces glabratus, whereas 31 species were differentially represented in controls, including Penicillium spp., Candida sake, and Clavispora lusitaniae. Histoplasma capsulatum, an endemic pathogen in the region, was more prevalent in PLWH and associated with low CD4⁺ T cell counts. Dirichlet multinomial mixture analysis revealed two mycobiotypes: M1, with a balanced fungal composition predominating in controls, and M2, dominated by Candida species and present in PLWH. These findings provide novel insights into gut mycobiota alterations in severely immunosuppressed PLWH in Argentina, highlighting Candida-driven dysbiosis and the regional relevance of H. capsulatum.