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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dc.contributor.authorHughes, Sean M.
dc.contributor.authorLevy, Claire N.
dc.contributor.authorCalienes, Fernanda L.
dc.contributor.authorStekler, Joanne D.
dc.contributor.authorPandey, Urvashi adik
dc.contributor.authorVojtech, Lucia
dc.contributor.authorBerard, Alicia R.
dc.contributor.authorBirse, Kenzie
dc.contributor.authorNoel-Romas, Laura
dc.contributor.authorRichardson, Brian
dc.contributor.authorGolden, Jackelyn B.
dc.contributor.authorCartwright, Michael
dc.contributor.authorCollier, Ann C.
dc.contributor.authorStevens, Claire E.
dc.contributor.authorCurlin, Marcel E.
dc.contributor.authorHoltz, Timothy H.
dc.contributor.authorMugo, Nelly
dc.contributor.authorIrungu, Elizabeth
dc.contributor.authorKatabira, Elly
dc.contributor.authorMuwonge, Timothy
dc.contributor.authorLama, Javier R.
dc.contributor.authorBaeten, Jared M.
dc.contributor.authorBurgener, Adam
dc.contributor.authorLingappa, Jairam R.
dc.contributor.authorMcElrath, M. Juliana
dc.contributor.authorMackelprang, Romel
dc.contributor.authorMcGowan, Ian
dc.contributor.authorCranston, Ross D.
dc.contributor.authorCameron, Mark J.
dc.contributor.authorHladik, Florian
dc.date.accessioned2023-02-08T18:15:50Z
dc.date.available2023-02-08T18:15:50Z
dc.date.issued2020
dc.description.abstractTenofovir 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.en_US
dc.identifier.citationHughes, 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.2020.100096en_US
dc.identifier.urihttps://doi.org/10.1016/j.xcrm.2020.100096
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/7654
dc.language.isoenen_US
dc.publisherCell Reports Medicineen_US
dc.subjectTreatmenten_US
dc.subjectAntiretroviral Drugs Inducesen_US
dc.subjectHIV Infectionen_US
dc.titleTreatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infectionen_US
dc.typeArticleen_US
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