RT Journal Article
SR Electronic
T1 Treatment with commonly used antiretroviral drugs induces a type I/III interferon signature in the gut in the absence of HIV infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 701961
DO 10.1101/701961
A1 Sean M. Hughes
A1 Claire N. Levy
A1 Fernanda L. Calienes
A1 Joanne D. Stekler
A1 Urvashi Pandey
A1 Lucia Vojtech
A1 Alicia R. Berard
A1 Kenzie Birse
A1 Laura Noël-Romas
A1 Brian Richardson
A1 Jackelyn B. Golden
A1 Michael Cartwright
A1 Ann C. Collier
A1 Claire E. Stevens
A1 Marcel E. Curlin
A1 Timothy H. Holtz
A1 Nelly Mugo
A1 Elizabeth Irungu
A1 Elly Katabira
A1 Timothy Muwonge
A1 Javier R. Lama
A1 Jared M. Baeten
A1 Adam Burgener
A1 Jairam R. Lingappa
A1 M. Juliana McElrath
A1 Romel Mackelprang
A1 Ian McGowan
A1 Ross D. Cranston
A1 Mark J. Cameron
A1 Florian Hladik
YR 2020
UL http://biorxiv.org/content/early/2020/08/03/701961.abstract
AB Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here we assessed the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induced type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r=0.91) and between the rectum and duodenum (r=0.81). Gene set testing also indicated stimulation of type I/III pathways in the ectocervix, as well as of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence staining confirmed IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN-I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.Competing Interest StatementJMB is on advisory boards for Gilead Sciences, Merck and Janssen. IM is the Chief Medical Officer of Orion Biotechnology. All other authors report no conflicts.