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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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Title: Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection
Authors: Sean M. Hughes, Claire N. Levy, Fernanda L. Calienes, Joanne D. Stekler, Urvashi Pandey, Lucia Vojtech, Alicia R. Berard, Kenzie Birse, Laura Noël-Romas, Brian Richardson, Jackelyn B. Golden, Michael Cartwright, Ann C. Collier, Claire E. Stevens, Marcel E. Curlin, Timothy H. Holtz, Nelly Mugo, Elizabeth Irungu, Elly Katabira, Timothy Muwonge, Javier R. Lama, Jared M. Baeten, Adam Burgener, Jairam R. Lingappa, M. Juliana McElrath, Romel Mackelprang, Ian McGowan, Ross D. Cranston, Mark J. Cameron, Florian Hladik
Source: Cell Reports Medicine, Vol 1, Iss 6, Pp 100096- (2020)
Publisher Information: Elsevier, 2020.
Publication Year: 2020
Collection: LCC:Medicine (General)
Subject Terms: HIV, HIV cure, antiretroviral treatment, ART, tenofovir, interferon, Medicine (General), R5-920
More Details: Summary: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2666-3791
Relation: http://www.sciencedirect.com/science/article/pii/S2666379120301221; https://doaj.org/toc/2666-3791
DOI: 10.1016/j.xcrm.2020.100096
Access URL: https://doaj.org/article/fc2ea90cdfe548fd8b58abc0db29d044
Accession Number: edsdoj.fc2ea90cdfe548fd8b58abc0db29d044
Database: Directory of Open Access Journals
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  Data: Summary: 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.
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