Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection
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Date
2020
Journal Title
Journal ISSN
Volume Title
Publisher
Cell Reports Medicine
Abstract
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
assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal
and one with cervicovaginal biopsies. TDF/FTC induces 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 indicates
stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA
sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm 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.
Description
Keywords
Treatment, Antiretroviral Drugs Induces, HIV Infection
Citation
Hughes, S. M., Levy, C. N., Calienes, F. L., Stekler, J. D., Pandey, U., Vojtech, L., ... & Hladik, F. (2020). Treatment with commonly used antiretroviral drugs induces a type I/III interferon signature in the gut in the absence of HIV infection. Cell Reports Medicine, 1(6), 100096. https://doi.org/10.1016/j.xcrm.2020.100096