Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV Prevention Trials Network-056).

Objectives: The purpose of this study was to evaluate the biologic stability of mucosal parameters that might be used as endpoints in phase I rectal safety studies. Methods: Sixteen male participants were enrolled into 4 groups defined by HIV status, viral load, and sexual activity. Each participant underwent 3 flexible sigmoidoscopics at 2-week intervals with collection of blood, intestinal biopsies, and rectal secretions. Intestinal histology, phenotypic characterization of mucosal mononuclear cells, cytokine messenger RNA (mRNA) profiles (RANTES, interferon-gamma [IFN gamma], and interleukin-10), and immunoglobulin secretion were assessed. Intraclass correlation (ICC) was calculated to assess endpoint stability. Results: Qualitative histology demonstrated minimal inflammation in >95% of biopsies and remained stable throughout the study period.]CC for the tissue cytokine mRNA measurements and several T-cell phenotypic markers was >0.7, indicating stability over time. Mucosal CD4 lymphopenia was seen in the HIV-positive participants and was more pronounced in those with higher viral loads. Modest differences were observed for cytokine expression (IFN-gamma) and T-cell phenotype (CD3, CD4, CD8, CD19, CD4/CCR5, and CD4/CD38) between the tissue samples collected at 10 and 30 cm. Conclusions: These data help to provide a rationale for the selection of endpoints for future phase I rectal safety studies.