Title
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection
Date Issued
22 September 2020
Access level
open access
Resource Type
journal article
Author(s)
Hughes S.M.
Levy C.N.
Calienes F.L.
Stekler J.D.
Pandey U.
Vojtech L.
Berard A.R.
Birse K.
Noël-Romas L.
Richardson B.
Golden J.B.
Cartwright M.
Collier A.C.
Stevens C.E.
Curlin M.E.
Holtz T.H.
Mugo N.
Irungu E.
Katabira E.
Muwonge T.
Baeten J.M.
Burgener A.
Lingappa J.R.
McElrath M.J.
Mackelprang R.
McGowan I.
Cranston R.D.
Cameron M.J.
Hladik F.
Publisher(s)
Cell Press
Abstract
Many people take the antiretroviral drugs tenofovir and emtricitabine to prevent and treat HIV infection. Hughes et al. show that these medications induce genes and proteins associated with type I/III interferon pathways in the gut. This effect may contribute to HIV inhibition but could also cause chronic immune activation.
Volume
1
Issue
6
Language
English
OCDE Knowledge area
Farmacología, Farmacia
Dermatología, Enfermedades venéreas
Subjects
Scopus EID
2-s2.0-85096573619
PubMed ID
Source
Cell Reports Medicine
ISSN of the container
26663791
Sponsor(s)
We wish to express gratitude to all of the study volunteers for their participation. We are grateful to Max Abou and Lauren Girard for proteomic wet lab support as well as Stuart McCorrister and Garrett Westmacott for mass spectrometry technical support. We acknowledge the Fred Hutchinson Experimental Histopathology (Sunni Farley, Savanh Chanthaphavong, and Li-Ya Huang) and Genomics (Cassie Sather and Crissa Bennett) core facilities for their assistance. This work was funded by NIH R01AI116292 (to F.H.), NIH R01AI111738 (to J.R. Lingappa), the Bill and Melinda Gates Foundation grant no. 47674 (to J.M.B.), NIH R01AI134293 (to R.M.), NIH AI027757 (to J.M.B.), NIH AI069481 (to A.C.C. and M.J.M.). M.J.C. and I.M. were supported by the Microbicide Trials Network (UM1AI068633, Sharon Hillier, principal investigator). A.B. was supported by the Canadian Institutes of Health Research (154042) and NIH (R01DK112254). This work was also supported by the Emory-Centers for Disease Control and Prevention (CDC) HIV/AIDS Clinical Trials Unit Grant award no. UM1AI069418 from the NIH (National Institute of Allergy and Infectious Diseases [NIAID]).The ddPCR portion of this work was supported by a grant from the James B. Pendleton Charitable Trust. The National Cancer Institute (NCI) 5 P30 CA015704-44 Cancer Center Support Grant supported the Fred Hutchinson Experimental Histopathology core facility. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies or the CDC. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The corresponding author had full access to all of the data in the study and had the final responsibility for the decision to submit for publication. Data Curation, S.M.H. C.N.L. A.R.B. K.B. L.N.R. B.R. J.B.G. and M.C.; Formal Analysis, S.M.H. and C.N.L.; Funding Acquisition, J.M.B. J.R. Lingappa, I.M. R.D.C. and F.H.; Investigation, S.M.H. C.N.L. F.L.C. U.P. A.R.B. K.B. L.N.-R. B.R. J.B.G. and M.C.; Methodology, S.M.H. U.P. and F.H.; Project Administration, S.M.H. and F.H.; Resources, F.L.C. J.D.S. A.C.C. C.E.S. M.E.C. T.H.H. N.M. E.I. E.K. T.M. J.R. Lama, J.M.B. J.R. Lingappa, R.M. I.M. and R.D.C.; Software, S.M.H. and C.N.L.; Supervision, J.M.B. A.B. J.R. Lingappa, M.J.M. M.J.C. and F.H.; Visualization, S.M.H.; Writing ? Original Draft, S.M.H. and F.H.; Writing ? Review & Editing, S.M.H. C.N.L. J.D.S. L.V. B.R. J.B.G. A.C.C. M.E.C. T.H.H. J.M.B. J.R. Lingappa, I.M. R.D.C. M.J.C. and F.H. J.M.B. is on the advisory boards of Gilead Sciences, Merck, and Janssen. I.M. is the Chief Medical Officer of Orion Biotechnology. All of the other authors declare no competing interests.
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