Project 3: PREVENT: A first-in-human clinical trial of Griffithsin, an HIV entry

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The overarching goal of the PREVENT Program is to develop a Griffithsin (GRFT) rectal gel that could be used prior to receptive anal intercourse (RAI) to reduce the risk of HIV infection by men who have sex with men (MSM). Project 3 will conduct a randomized, placebo-controlled pre-Phase 1 human study to measure GRFT safety, pharmacokinetics (PK) and pharmacodynamics (PD). We will recruit 18 healthy men to participate in a prospective trial to evaluate GRFT carbopol gel versus a matched placebo in a 2:1 randomization design. The study will address traditional product safety and PK parameters, but we will also evaluate the effect of the product on adaptive immunity to GRFT by conducting a three stage study. The first stage will involve a single drug exposure. In Stages 2 and 3, men will receive 5 doses of gel product on consecutive days separated by a two week washout period. Rectal biopsies and other samples taken at baseline and during Stages 1-3 will be used to characterize mucosal responses to GRFT including enumeration of HIV target cells and detection of representative HIV receptors and epithelial junction proteins in the rectumby immunohistochemistry and flow cytometry. The biopsies will also be used for a PD assessment by ex vivo challenge of the tissue with HIV-1. Additionally, we will employ a systems biology approach, including transcriptomics, proteomics and microbiome analysis, to analyze the global impact of GRFT treatment on the mucosal environment in the rectum.