{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Romas L"],"funding":["NICHD NIH HHS","NIAID NIH HHS","NIMH NIH HHS","CIHR"],"pagination":["1005-1015"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5067863"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(10-11)"],"pubmed_abstract":["Rectal use of a 1% tenofovir (TFV) gel is currently being evaluated for HIV prevention. While careful assessment of mucosal safety of candidate microbicides is a primary concern, tools to assess mucosal toxicity are limited. Mass spectrometry-based proteomics is a sensitive and high-throughput technique that can provide in-depth information on inflammation processes in biological systems. In this study, we utilized a proteomics approach to characterize mucosal responses in study participants involved in a phase 1 clinical trial of a rectal TFV-based gel. Project Gel was a phase 1 randomized (1:1), double-blind, multisite, placebo-controlled trial in which 24 participants received rectal TFV or a universal placebo [hydroxyethyl cellulose (HEC)] over a course of 8 daily doses. Rectal mucosal swabs were collected after 0, 1, and 8 doses and were analyzed by label-free tandem mass spectrometry. Differential protein expression was evaluated using a combination of paired (time-effects) and unpaired (across study arm) t-tests, and multivariate [least absolute shrinkage and selection operator (LASSO)] modeling. Within the TFV arm, 7% (17/249, p < .05) and 10% (25/249, p < .05) of total proteins changed after 1 and 8 daily applications of TFV gel, respectively, compared to 3% (7/249, p < .05) and 6% (16/249, p < .05) in the HEC arm. Biofunctional analysis associated TFV use with a decrease in epidermal barrier proteins (adj. p = 1.21 × 10<sup>-10</sup>). Multivariate modeling identified 13 proteins that confidently separated TFV gel users (100% calibration and 96% cross-validation accuracy), including the epithelial integrity factors (FLMNB, CRNN, CALM), serpins (SPB13, SPB5), and cytoskeletal proteins (VILI, VIME, WRD1). This study suggested that daily rectal applications of a 1% TFV gel may be associated with mucosal proteome changes involving epidermal development. Further assessment of more extended use of TFV-gel is recommended to validate these initial associations."],"journal":["AIDS research and human retroviruses"],"pubmed_title":["Rectal 1% Tenofovir Gel Use Associates with Altered Epidermal Protein Expression."],"pmcid":["PMC5067863"],"funding_grant_id":["R01 HD059533","UM1 AI069415","P30 MH043520","OCB134115"],"pubmed_authors":["Abou M","Febo I","Carballo-Dieguez A","McGowan I","Romas L","Giguere R","Burgener A","Birse K","Cranston RD","Westmacott G","Mayer KH"],"additional_accession":[]},"is_claimable":false,"name":"Rectal 1% Tenofovir Gel Use Associates with Altered Epidermal Protein Expression.","description":"Rectal use of a 1% tenofovir (TFV) gel is currently being evaluated for HIV prevention. While careful assessment of mucosal safety of candidate microbicides is a primary concern, tools to assess mucosal toxicity are limited. Mass spectrometry-based proteomics is a sensitive and high-throughput technique that can provide in-depth information on inflammation processes in biological systems. In this study, we utilized a proteomics approach to characterize mucosal responses in study participants involved in a phase 1 clinical trial of a rectal TFV-based gel. Project Gel was a phase 1 randomized (1:1), double-blind, multisite, placebo-controlled trial in which 24 participants received rectal TFV or a universal placebo [hydroxyethyl cellulose (HEC)] over a course of 8 daily doses. Rectal mucosal swabs were collected after 0, 1, and 8 doses and were analyzed by label-free tandem mass spectrometry. Differential protein expression was evaluated using a combination of paired (time-effects) and unpaired (across study arm) t-tests, and multivariate [least absolute shrinkage and selection operator (LASSO)] modeling. Within the TFV arm, 7% (17/249, p < .05) and 10% (25/249, p < .05) of total proteins changed after 1 and 8 daily applications of TFV gel, respectively, compared to 3% (7/249, p < .05) and 6% (16/249, p < .05) in the HEC arm. Biofunctional analysis associated TFV use with a decrease in epidermal barrier proteins (adj. p = 1.21 × 10<sup>-10</sup>). Multivariate modeling identified 13 proteins that confidently separated TFV gel users (100% calibration and 96% cross-validation accuracy), including the epithelial integrity factors (FLMNB, CRNN, CALM), serpins (SPB13, SPB5), and cytoskeletal proteins (VILI, VIME, WRD1). This study suggested that daily rectal applications of a 1% TFV gel may be associated with mucosal proteome changes involving epidermal development. Further assessment of more extended use of TFV-gel is recommended to validate these initial associations.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Oct/Nov","modification":"2025-04-05T15:56:00.088Z","creation":"2019-03-27T02:26:57Z"},"accession":"S-EPMC5067863","cross_references":{"pubmed":["27316778"],"doi":["10.1089/AID.2015.0381"]}}