Distinct mucosal and systemic immunological characteristics in transgender women potentially relating to HIV acquisition.

Overview

Transgender women (TGW) are disproportionally affected by HIV infection, with a global estimated prevalence of 19.9%, often attributed to behavioral risk factors, with less known about biological factors. We evaluated potential biological risk factors for HIV acquisition in TGW at the sites of viral entry by assessing immune parameters of neovaginal surface and gut mucosa. The neovagina in TGW, compared to the vagina in CW, shows distinct cell composition and may pose a more inflammatory environment, evidenced by increased CD4+ T cell activation and higher levels of soluble markers of inflammation (CRP, sCD30). Increased inflammation may be driven by microbiome composition, showing a greater abundance of Prevotella and a higher Shannon diversity. In addition, we have observed higher frequency of CD4+CCR5+ target cells and decreased DNA methylation of the CCR5 gene in the gut mucosa of TGW compared to CW and MSM which was inversely correlated with testosterone levels. The rectal microbiome composition in TGW appears to favor a proinflammatory milieu as well as mucosal barrier disruption. Thus, it is possible that increased inflammation and higher frequencies of CCR5-expressing target cells at sites of mucosal viral entry may contribute to increased risk of HIV acquisition in TGW, with further validation in larger studies warranted.