Acceptability of UC781 gel as a rectal microbicide among HIV-uninfected women and men.

We studied the overall acceptability of UC781 gel formulation when applied rectally. Ten women and twenty-six men, all HIV-uninfected, were enrolled in a Phase 1, randomized, blinded, placebo-controlled safety and acceptability study of the vaginal microbicide gel UC781 applied rectally. Participants were randomized to three groups: 0.1% UC781 gel, 0.25% UC781 gel, or a placebo gel. Acceptability was assessed using structured questionnaires and qualitative in-depth interviews. After using UC781 gel rectally for seven consecutive days, participants' reports suggest that a UC781 gel formulation is highly acceptable and comparable to a placebo gel. The gels received favorable ratings overall and on attributes such as color, smell and consistency. All of the participants reported high intentions to use a gel like the one they used in this study. Acceptability research is essential in early phases of microbicide development to identify potential problems, understand user preferences, and introduce changes if needed.

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 1 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 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. RESULTS: 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. CONCLUSIONS: These data help to provide a rationale for the selection of endpoints for future phase 1 rectal safety studies.