Mentored Scientist Award

People with HIV (PWH) experience excess liver fibrosis even in the absence of viral hepatitis or heavy alcohol use. Emerging evidence implicates gut barrier dysfunction and microbial translocation as central drivers of chronic immune activation and downstream hepatic injury. However, the specific gut microbial features associated with circulating markers of microbial translocation and liver fibrosis in treated PWH remain poorly defined. This study will leverage well-characterized data from the MACS/WIHS Combined Cohort Study (MWCCS) including16S rRNA sequencing of stool samples . Aim 1 will identify gut microbial taxa and community-level features associated with circulating biomarkers of microbial translocation and systemic inflammation (n=450). Multivariable models will evaluate associations between microbial features and biomarker levels, adjusting for metabolic and HIV-related covariates. Aim 2 will determine whether gut microbiome features associated with microbial translocation are independently associated with prevalent liver fibrosis and steatosis, as measured by vibration controlled attenuation parameter (VCTE, n=750), and whether these relationships are modified by commonly used medications (proton pump inhibitors, GLP-agonists).

This project will define microbial signatures linked to translocation and fibrosis in PWH and identify medication exposures that may amplify or mitigate these associations. Findings will generate preliminary data for longitudinal and mechanistic studies and inform future microbiome-targeted interventions. By integrating microbiome, biomarker, and noninvasive liver data within an HIV
cohort, this RAP award will establish a scalable framework for investigating gut–liver axis dysfunction in HIV-associated liver disease.