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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 46; no. 4; p. 417
• Main Authors: McGowan, Ian, Elliott, Julie, Cortina, Galen, Tanner, Karen, Siboliban, Chomchay, Adler, Amy, Cho, Daniel, Boscardin, W John, Soto-Torres, Lydia, Anton, Peter A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2007
• Subjects: Administration, Rectal; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Antigens, CD - analysis; Clinical Trials as Topic; Cytokines - genetics; Endoscopy; HIV Seronegativity; HIV Seropositivity - immunology; HIV Seropositivity - physiopathology; Humans; Immunoglobulin G - analysis; Immunoglobulins - analysis; Inflammation - chemically induced; Inflammation - immunology; Inflammation - pathology; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Male; RNA, Messenger - genetics
• ISSN: 1525-4135
• DOI: 10.1097/QAI.0b013e318156ef16

The purpose of this study was to evaluate the biologic stability of mucosal parameters that might be used as endpoints in phase 1 rectal safety studies. Sixteen male participants were enrolled into 4 groups defined by HIV status, viral load, and sexual activity. Each participant underwent 3 flexible sigmoidoscopies 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 [IFNgamma], and interleukin-10), and immunoglobulin secretion were assessed. Intraclass correlation (ICC) was calculated to assess endpoint stability. Qualitative histology demonstrated minimal inflammation in >95% of biopsies and remained stable throughout the study period. ICC 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 (IFNgamma) and T-cell phenotype (CD3, CD4, CD8, CD19, CD4/CCR5, and CD4/CD38) between the tissue samples collected at 10 and 30 cm. These data help to provide a rationale for the selection of endpoints for future phase 1 rectal safety studies.