Persistent inflammatory markers existing with HIV-1 reservoirs in antiretroviral therapy treated HIV-1 individuals

Despite successful viral suppression with antiretroviral therapy, individuals infected with human immunodeficiency virus type 1(HIV-1) develop chronic inflammation, which may be related to immune activation due to the persistence of the viral reservoir. However, the mechanisms linking HIV-1 reservoirs to inflammation are not fully understood. Here, we comprehensively analyzed 92 inflammation-related proteins (IRPs) in HIV-1-infected individuals using Olink proteomics, including 16 longitudinal pre- and post-treatment participants, 32 long-term treatments (more than 8 years), and age-matched healthy controls. We identified 16 IRPs whose expression remained elevated after treatment regardless of treatment duration, and finally flow validation revealed that MCP-2, CD8A, and TNFRSF9 were significantly positively correlated with HIV-1 DNA, independently of age and sex, whereas CXCL11 was significantly negatively correlated with immune recovery in HIV-1 individuals. The results indicated that the persistence of HIV-1 reservoirs is closely associated with a unique inflammatory environment, which providing novel insights into HIV-1 reservoirs and inflammation.