Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection

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

doi:10.1016/j.xcrm.2020.100096

Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection

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 MuwongeJavier 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

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	100096
Journal	Cell Reports Medicine
Volume	1
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2020.100096
State	Published - Sep 22 2020

Keywords

ART
HIV
HIV cure
ISG15
antiretroviral treatment
chronic immune activation
gut
interferon
tenofovir

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Medicine(all)

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10.1016/j.xcrm.2020.100096

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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., ... 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

Hughes, SM, Levy, CN, Calienes, FL, Stekler, JD, Pandey, U, Vojtech, L, Berard, AR, Birse, K, Noël-Romas, L, Richardson, B, Golden, JB, Cartwright, M, Collier, AC, Stevens, CE, Curlin, ME, Holtz, TH, Mugo, N, Irungu, E, Katabira, E, Muwonge, T, Lama, JR, Baeten, JM, Burgener, A, Lingappa, JR, McElrath, MJ, Mackelprang, R, McGowan, I, Cranston, RD, Cameron, MJ & 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, vol. 1, no. 6, 100096. https://doi.org/10.1016/j.xcrm.2020.100096

@article{27a7596832a9474eb7aff4b9e9f5a01c,

title = "Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection",

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.",

keywords = "ART, HIV, HIV cure, ISG15, antiretroviral treatment, chronic immune activation, gut, interferon, tenofovir",

author = "Hughes, {Sean M.} and Levy, {Claire N.} and Calienes, {Fernanda L.} and Stekler, {Joanne D.} and Urvashi Pandey and Lucia Vojtech and Berard, {Alicia R.} and Kenzie Birse and Laura No{\"e}l-Romas and Brian Richardson and Golden, {Jackelyn B.} and Michael Cartwright and Collier, {Ann C.} and Stevens, {Claire E.} and Curlin, {Marcel E.} and Holtz, {Timothy H.} and Nelly Mugo and Elizabeth Irungu and Elly Katabira and Timothy Muwonge and Lama, {Javier R.} and Baeten, {Jared M.} and Adam Burgener and Lingappa, {Jairam R.} and McElrath, {M. Juliana} and Romel Mackelprang and Ian McGowan and Cranston, {Ross D.} and Cameron, {Mark J.} and Florian Hladik",

note = "Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = sep,

day = "22",

doi = "10.1016/j.xcrm.2020.100096",

language = "English (US)",

volume = "1",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection

AU - Hughes, Sean M.

AU - Levy, Claire N.

AU - Calienes, Fernanda L.

AU - Stekler, Joanne D.

AU - Pandey, Urvashi

AU - Vojtech, Lucia

AU - Berard, Alicia R.

AU - Birse, Kenzie

AU - Noël-Romas, Laura

AU - Richardson, Brian

AU - Golden, Jackelyn B.

AU - Cartwright, Michael

AU - Collier, Ann C.

AU - Stevens, Claire E.

AU - Curlin, Marcel E.

AU - Holtz, Timothy H.

AU - Mugo, Nelly

AU - Irungu, Elizabeth

AU - Katabira, Elly

AU - Muwonge, Timothy

AU - Lama, Javier R.

AU - Baeten, Jared M.

AU - Burgener, Adam

AU - Lingappa, Jairam R.

AU - McElrath, M. Juliana

AU - Mackelprang, Romel

AU - McGowan, Ian

AU - Cranston, Ross D.

AU - Cameron, Mark J.

AU - Hladik, Florian

N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2020 The Author(s)

PY - 2020/9/22

Y1 - 2020/9/22

N2 - 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.

AB - 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.

KW - ART

KW - HIV

KW - HIV cure

KW - ISG15

KW - antiretroviral treatment

KW - chronic immune activation

KW - gut

KW - interferon

KW - tenofovir

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JO - Cell Reports Medicine

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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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