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

Adult Anti-HIV Agents / administration & dosage Anti-Retroviral Agents / therapeutic use Antiretroviral Therapy, Highly Active / methods Emtricitabine / administration & dosage Female Gastrointestinal Microbiome / drug effects Gene Expression / genetics HIV / drug effects HIV Infections / drug therapy Humans Interferon Type I / therapeutic use Male Middle Aged Pharmaceutical Preparations Pre-Exposure Prophylaxis / methods Tenofovir / administration & dosage Transcriptome / drug effects
ART HIV HIV cure ISG15 antiretroviral treatment chronic immune activation gut interferon tenofovir

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
22 09 2020
Historique:
received: 14 02 2020
revised: 09 07 2020
accepted: 24 08 2020
entrez: 5 10 2020
pubmed: 6 10 2020
medline: 6 10 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1016/j.xcrm.2020.100096 PMID: 33015651 PMC: PMC7511692
pubmed: 33015651
doi: 10.1016/j.xcrm.2020.100096
pii: S2666-3791(20)30122-1
pmc: PMC7511692
doi:

Substances chimiques

Anti-HIV Agents 0
Anti-Retroviral Agents 0
Interferon Type I 0
Pharmaceutical Preparations 0
Tenofovir 99YXE507IL
Emtricitabine G70B4ETF4S

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

100096

Subventions

Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068633
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116292
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069481
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027757
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112254
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069418
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134293
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068633
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069481
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111738
Pays : United States

Informations de copyright

© 2020 The Author(s).

Déclaration de conflit d'intérêts

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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Auteurs

Sean M Hughes (SM)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

Claire N Levy (CN)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

Fernanda L Calienes (FL)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Joanne D Stekler (JD)

Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.

Urvashi Pandey (U)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

Lucia Vojtech (L)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

Alicia R Berard (AR)

Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.

Kenzie Birse (K)

Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.

Laura Noël-Romas (L)

Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.

Brian Richardson (B)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Jackelyn B Golden (JB)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Michael Cartwright (M)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Ann C Collier (AC)

Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

Claire E Stevens (CE)

Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

Marcel E Curlin (ME)

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand.
Department of Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, Portland, OR, USA.

Timothy H Holtz (TH)

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand.

Nelly Mugo (N)

Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
Center for Clinical Research (CCR), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
Department of Global Health, University of Washington, Seattle, WA, USA.

Elizabeth Irungu (E)

Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.

Elly Katabira (E)

Infectious Disease Institute, Makerere University, Kampala, Uganda.

Timothy Muwonge (T)

Infectious Disease Institute, Makerere University, Kampala, Uganda.

Javier R Lama (JR)

Asociación Civil Impacta Salud y Educación, Lima, Peru.

Jared M Baeten (JM)

Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.

Adam Burgener (A)

Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Unit of Infectious Diseases, Department of Medicine Solna, Centre for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Jairam R Lingappa (JR)

Department of Pediatrics, University of Washington, Seattle, WA, USA.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.

M Juliana McElrath (MJ)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.

Romel Mackelprang (R)

Department of Global Health, University of Washington, Seattle, WA, USA.

Ian McGowan (I)

Orion Biotechnology, Ottawa, ON, Canada.
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Ross D Cranston (RD)

Department of Infectious Diseases and Dermatology, University of Barcelona, Barcelona, Spain.

Mark J Cameron (MJ)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Florian Hladik (F)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Thérapie antirétrovirale hautement active › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Nucléosides pyrimidiques › Désoxycytidine › Emtricitabine › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Biodiversité › Biote › Microbiote › Microbiome gastro-intestinal › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Préparations pharmaceutiques › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Prophylaxie pré-exposition › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Adénine › Ténofovir › Treatment with Commonly Used Antiretroviral...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Treatment with Commonly Used Antiretroviral...