Skin microbiome variation in people living with HIV: associations with antiretroviral therapy and host factors.

Introduction: The skin microbiome plays a key role in cutaneous immunity and is shaped by host immune status. HIV infection is associated with immune dysfunction and dermatological disease, yet its impact on the skin microbiome and the modifying effect of antiretroviral therapy (ART) remain incompletely defined. This prospective observational study conducted in Indonesia aimed to characterize differences in skin microbiome composition across HIV status and ART exposure and relate these profiles to clinical parameters. Methods: Skin swabs were obtained from sebaceous (posterior neck) and dry (dorsal forearm) sites in HIV-ART-naïve individuals, people living with HIV on ART, and HIV-negative controls, and analyzed using 16S rRNA gene sequencing. Microbial diversity and community structure were assessed using Bray-Curtis dissimilarity, PERMANOVA, and differential abundance testing with ANCOM-BC2, with multivariable models adjusting for demographic, clinical, behavioral, and anatomical factors and subgroup analyses by body mass index, skincare habits, and sampling site. Results: In total, 488 samples from 244 participants were analyzed. Both HIV groups showed significantly reduced alpha diversity compared with controls, and overall community composition differed by HIV status, although sampling site explained a larger proportion of variation. Across groups, the microbiome was dominated by Conclusions: These findings suggest that HIV infection is associated with subtle but consistent alterations in the skin microbiome within the context of strong site-specific skin microenvironments. Longitudinal studies integrating functional profiling and host markers of cutaneous barrier integrity and inflammation are needed to clarify their clinical implications.