Crosstalk Among Oral and Gastrointestinal Soluble Innate Factors, HIV and Microbes

1New York University College of Dentistry, 2Rockefeller University, 3Aaron Diamond AIDS Research Center, 4New York University/ Bellevue Hospital Medical Center, New York, NY

This study will recruit 85 HIV positive, antiretroviral naïve subjects and 75 HIV negative age/gender/race matched subjects. The entire GI tract is sampled (oral, esophagus, gastric body, duodenum, and colon). Subsequently, the HIV positive subjects begin antiretroviral therapy and sampled at timed intervals for up to 4 years. The study includes 4 research projects: Project 1 (P.I. David Ho) is determining the proteome in oral and GI samples. This will include top-down and bottom-up proteomics and a delineation of the peptidome. The goal is to compare the proteomes between HIV+ and HIV- individuals and also in HIV+ individuals before and after antiretroviral therapy, Project 2 (P.I. Yihong Li/Deepak Saxena) will analyze the oral microbiome in saliva, buccal mucosa, and plaque. The study will evaluate the diversity of the microflora, and also sequence both cultivable and non-cultivable microorganisms that are determined to change between the experimental groups (HIV+ compared to HIV-, and HIV+ before and after therapy. Project 3 (P.I. Michael Poles/Zheiheng Pei) will describe the remaining GI microbiome, and similar to Project 2 will establish patterns in cultivable and non-cultivable microorganisms throughout the GI track. Project 4 (P.I. Daniel Malamud) is focusing on determining alterations in cytokines and the innate immune system. In this study, unique proteins identified in Project 1, and specific bacteria identified in Projects 2 and 3 will be evaluated by testing the anti-bacterial activity of proteins identified by Project 1 on specific bacteria identified in Projects 2 and 3. The hypothesis being tested is that elevated specific proteins at GI sites will have anti-bacterial activity on those microorganisms found to decrease after HIV infection and/or therapy. In addition, a collection of skin samples for microbiomic studies are collected (P.I., Martin Blaser). This study will allow the investigators to track and identify changes in the skin microbiome between HIV+ and HIV- subjects, as well as tracking those changes over time. The overall goal is to define the interactions between host defense molecules and bacteria in HIV infection and subsequent antiretroviral therapy.

Supported by NIDCR U19DE018385, NYUCD CFAR, NIAID 5P30A1027742