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Tuesday, March 6, 2012

Improved rectal microbicide for PrEP is safe and well-tolerated

PRN Report from 19th CROI:

In a late breaker report at the Conference on Retrovirology and Opportunistic Infections in Seattle, Ian McGowan from the University of Pittsburgh presented data from a study designed to assess the safety, adherence, and acceptability of a reduced glycerin formulation of tenofovir (TDF) 1% gel that is currently being developed as a rectal microbicide for HIV prevention. A nonoxynol-9 (N9) arm was included as a positive control for the mucosal safety assays.

The study recruited 65 participants (45 men and 20 women) aged 18 to 61 from 2 US sites (Pittsburgh, Pennsylvania, Birmingham, Alabama, and Boston, Massachusetts). Participants were randomized 1:1:1:1 to receive a reduced glycerin TDF 1% gel, a HEC placebo gel (HEC), a 2% N9, or a no treatment arm (No Rx). Participants were evaluated at baseline, after a single dose, and after 7 daily doses of study product. Systemic and mucosal safety, acceptability, and adherence were evaluated at all 3 visits. Comprehensive mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), flow cytometry of mucosal T cell phenotype, and rectal microflora. All mucosal assays were performed on biopsies collected at 9 and 15 cm from the anal margin. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response respectively.

A total of 16 (TDF), 17 (HEC), 16 (N9), and 16 (No Rx) sexually abstinent participants were enrolled in the study. Product adherence was ≥94%. Adverse events were generally mild (G1, n = 121, 80%) or moderate (G2, n = 27, 18%). In the No Rx arm or before product use, 2 G3 and 1 G4 events occurred. There was no significant difference in the prevalence of adverse events across the 4 arms of the study. Likelihood of future product use (acceptability) was 86.7% (TDF), 93.3% (HEC), and 62.5% (N9). Fecal calprotectin and epithelial sloughing did not alter during the study. In contrast, significant changes were seen in mucosal cytokine/chemokine expression, T cell phenotype, and rectal microflora, which were mostly confined to the N9 arm.

Dr McGowan concluded that this reduced glycerin formulation of 1% TDF was safe and well tolerated and should be advanced to phase 2 rectal microbicide development (MTN-017). The interpretation of the mucosal safety data is complex, but as expected most changes indicating irritation of the mucosa occurred in the N9 arm. Further evaluation of these parameters will form part of the MTN-017 Phase 2 study where TDF 1% gel will be administered rectally for up to 8 weeks.

McGowan I, Hoesley C, Andrew P, Janocko L, Dai J, Carballo-Dieguez A, Kunjara Na Ayudhya R, Piper J, Cranston R, Mayer K. MTN-007: A Phase 1 Randomized, Double-blind, Placebo-controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel. Presented March 6, 2012 at the 19th CROI, Seattle, WA. Oral Abstract #34LB.

Source: Source: Reporting from Seattle for PRN News: James Braun DO