Abstract
BACKGROUND: HIV infection alters host immunity, including the oral environment, leading to microbial imbalance and increased risk of opportunistic infections. Although antiretroviral therapy (ART) improves immune function, its effect on the oral microbiome remains unclear, particularly in Indonesia. This study investigated oral microbiome composition in people living with HIV and its associations with ART status, age, and sex. METHODS: In this cross-sectional study, oral rinse samples from 245 adults (115 HIV-on-ART, 15 HIV-ART-naïve, and 115 HIV-negative controls) were analysed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance (ANCOM-BC2), and multivariable associations (PERMANOVA) were assessed. RESULTS: The oral microbiome differed significantly between HIV-positive groups and controls (PERMANOVA p = 0.001, R² = 1.8%). HIV-ART-naïve individuals exhibited the highest alpha diversity and enrichment of pro-inflammatory genera, including Fusobacterium, Alloprevotella, and Staphylococcus. ART-treated individuals displayed a partial shift toward the control profile but retained persistent depletion of bacteria such as Filifactor and (Eubacterium) saphenum. Multivariate analysis identified HIV status, age, and sex as independent contributors to microbial variation. CONCLUSION: HIV infection is associated with a distinct oral dysbiosis characterised by an increase in opportunistic pathogens and reduction in commensal bacteria. HIV-on-ART individuals show a transitional shift towards the HIV-negative oral microbiome profiles. Our findings suggest that biological and/or demographic factors coupled to oral microbiome profiles may facilitate targeted interventions in the personalised management of oral health for individuals living with HIV.