title: A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007).
abstract: OBJECTIVE
  Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel.
  
  
  METHODS
  Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively.
  
  
  RESULTS
  Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms.
  
  
  CONCLUSIONS
  The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01232803.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America. imcgowan@pitt.edu
authors.forename: Ian
authors.initials: I
authors.lastname: McGowan
authors.forename: Craig
authors.initials: C
authors.lastname: Hoesley
authors.forename: Ross D
authors.initials: RD
authors.lastname: Cranston
authors.forename: Philip
authors.initials: P
authors.lastname: Andrew
authors.forename: Laura
authors.initials: L
authors.lastname: Janocko
authors.forename: James Y
authors.initials: JY
authors.lastname: Dai
authors.forename: Alex
authors.initials: A
authors.lastname: Carballo-Dieguez
authors.forename: Ratiya Kunjara Na
authors.initials: RK
authors.lastname: Ayudhya
authors.forename: Jeanna
authors.initials: J
authors.lastname: Piper
authors.forename: Florian
authors.initials: F
authors.lastname: Hladik
authors.forename: Ken
authors.initials: K
authors.lastname: Mayer
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000285:Administration, Rectal; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000068698:Tenofovir; D059467:Transcriptome / Q000187:drug effects; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine