TY - JOUR T1 - Oral tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis increases expression of type I/III interferon-stimulated factors in the gastrointestinal tract but not in the blood JF - bioRxiv DO - 10.1101/701961 SP - 701961 AU - Sean M. Hughes AU - Claire N. Levy AU - Fernanda Calienes AU - Joanne D. Stekler AU - Urvashi Pandey AU - Lucia Vojtech AU - Alicia R. Berard AU - Kenzie Birse AU - Laura Noel-Romas AU - Brian Richardson AU - Jackelyn B. Golden AU - Michael Cartwright AU - Ann C. Collier AU - Claire E. Stevens AU - Marcel E. Curlin AU - Timothy H. Holtz AU - Nelly Mugo AU - Elizabeth Irungu AU - Elly Katabira AU - Timothy Muwonge AU - Javier R. Lama AU - Jared M. Baeten AU - Adam Burgener AU - Jairam R. Lingappa AU - M. Juliana McElrath AU - Romel Mackelprang AU - Ian McGowan AU - Ross D. Cranston AU - Mark J. Cameron AU - Florian Hladik Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/07/701961.abstract N2 - Tenofovir disoproxil fumarate and emtricitabine are used for HIV treatment and pre-exposure prophylaxis. Previously, we found that topical rectal application of tenofovir 1% gel caused many gene expression changes. Here, we measured RNA and protein expression in several clinical trials of oral administration in HIV-uninfected individuals (using microarrays, RNAseq, droplet digital PCR, mass spectrometry, and microscopy). We found tens to hundreds of differentially expressed genes in the gastrointestinal tract, but none in the blood or female reproductive tract. In rectal samples from one trial, most of the 13 upregulated genes were related to type I/III interferon signaling. Similar changes were seen at the protein level in the same trial and in the duodenum and rectum in another trial. We conclude that tenofovir disoproxil fumarate and emtricitabine have little effect on gene expression in the blood or female reproductive tract but increase type I/III interferon signaling in the gut. This effect may enhance their anti-viral efficacy when used as pre-exposure prophylaxis, in particular to prevent rectal HIV transmission. However, it may also contribute to chronic immune activation and HIV reservoir maintenance in chronically treated people living with HIV. ER -