Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Hughes SM [original query] |
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Oral tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis increases expression of type I/III interferon-stimulated factors in the gastrointestinal tract but not in the blood (preprint)
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 . bioRxiv 2019 701961 Tenofovir disoproxil fumarate and emtricitabine are used for HIV treatment and pre-exposure prophylaxis. Previously, we found that topical rectal application of tenofovir 1% gel caused many gene expression changes. Here, we measured RNA and protein expression in several clinical trials of oral administration in HIV-uninfected individuals (using microarrays, RNAseq, droplet digital PCR, mass spectrometry, and microscopy). We found tens to hundreds of differentially expressed genes in the gastrointestinal tract, but none in the blood or female reproductive tract. In rectal samples from one trial, most of the 13 upregulated genes were related to type I/III interferon signaling. Similar changes were seen at the protein level in the same trial and in the duodenum and rectum in another trial. We conclude that tenofovir disoproxil fumarate and emtricitabine have little effect on gene expression in the blood or female reproductive tract but increase type I/III interferon signaling in the gut. This effect may enhance their anti-viral efficacy when used as pre-exposure prophylaxis, in particular to prevent rectal HIV transmission. However, it may also contribute to chronic immune activation and HIV reservoir maintenance in chronically treated people living with HIV. |
Treatment with commonly used antiretroviral drugs induces a type I/III interferon signature in the gut in the absence of HIV infection
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 . Cell Rep Med 2020 1 (6) 100096 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. |
Active tracing and monitoring of contacts associated with the first cluster of Ebola in the United States
Chung WM , Smith JC , Weil LM , Hughes SM , Joyner SN , Hall EM , Ritch J , Srinath D , Goodman E , Chevalier MS , Epstein L , Hunter JC , Kallen AJ , Karwowski MP , Kuhar DT , Smith C , Petersen LR , Mahon BE , Lakey DL , Schrag SJ . Ann Intern Med 2015 163 (3) 164-73 BACKGROUND: Following hospitalization of the first patient with Ebola virus disease diagnosed in the United States on 28 September 2014, contact tracing methods for Ebola were implemented. OBJECTIVE: To identify, risk-stratify, and monitor contacts of patients with Ebola. DESIGN: Descriptive investigation. SETTING: Dallas County, Texas, September to November 2014. PARTICIPANTS: Contacts of symptomatic patients with Ebola. MEASUREMENTS: Contact identification, exposure risk classification, symptom development, and Ebola. RESULTS: The investigation identified 179 contacts, 139 of whom were contacts of the index patient. Of 112 health care personnel (HCP) contacts of the index case, 22 (20%) had known unprotected exposures and 37 (30%) did not have known unprotected exposures but interacted with a patient or contaminated environment on multiple days. Transmission was confirmed in 2 HCP who had substantial interaction with the patient while wearing personal protective equipment. These HCP had 40 additional contacts. Of 20 community contacts of the index patient or the 2 HCP, 4 had high-risk exposures. Movement restrictions were extended to all 179 contacts; 7 contacts were quarantined. Seven percent (14 of 179) of contacts (1 community contact and 13 health care contacts) were evaluated for Ebola during the monitoring period. LIMITATION: Data cannot be used to infer whether in-person direct active monitoring is superior to active monitoring alone for early detection of symptomatic contacts. CONCLUSION: Contact tracing and monitoring approaches for Ebola were adapted to account for the evolving understanding of risks for unrecognized HCP transmission. HCP contacts in the United States without known unprotected exposures should be considered as having a low (but not zero) risk for Ebola and should be actively monitored for symptoms. Core challenges of contact tracing for high-consequence communicable diseases included rapid comprehensive contact identification, large-scale direct active monitoring of contacts, large-scale application of movement restrictions, and necessity of humanitarian support services to meet nonclinical needs of contacts. PRIMARY FUNDING SOURCE: None. |
Addressing needs of contacts of Ebola patients during an investigation of an Ebola cluster in the United States - Dallas, Texas, 2014
Smith CL , Hughes SM , Karwowski MP , Chevalier MS , Hall E , Joyner SN , Ritch J , Smith JC , Weil LM , Chung WM , Schrag S , Santibanez S . MMWR Morb Mortal Wkly Rep 2015 64 (5) 121-123 The first imported case of Ebola virus disease (Ebola) diagnosed in the United States was confirmed on September 30, 2014; two health care workers who cared for this patient subsequently developed Ebola. Since then, local, state, and federal health officials have continued to prepare for future imported cases, including developing strategies to identify and monitor persons who have had contact with an Ebola patient. This report describes some of the needs of persons who were contacts of Ebola patients in Texas. It is based on requests received from contacts in the course of daily contact tracing interactions and on how those needs were met through community partnerships. Meeting the needs of contacts of the Ebola patients was essential to successful contact tracing, which is critical to interrupting transmission. Although a formal needs assessment of contacts was not conducted, this report provides important information for preparing for an importation of Ebola. Anticipating the nonclinical needs of persons under public health surveillance includes addressing potential concerns about housing, transportation, education, employment, food, and other household needs. Ensuring necessary supports are in place for persons who are asked to refrain from entering public venues can impact their willingness to comply with voluntary and mandated quarantine orders. Engagement with a wide range of community partners, including businesses, schools, charitable foundations, community and faith-based organizations, and mental health resources would enhance public health emergency preparedness for Ebola by readying resources to meet these potential needs. |
Ebola virus disease cluster in the United States - Dallas County, Texas, 2014
Chevalier MS , Chung W , Smith J , Weil LM , Hughes SM , Joyner SN , Hall E , Srinath D , Ritch J , Thathiah P , Threadgill H , Cervantes D , Lakey DL . MMWR Morb Mortal Wkly Rep 2014 63 (46) 1087-8 Since March 10, 2014, Guinea, Liberia, and Sierra Leone have experienced the largest known Ebola virus disease (Ebola) epidemic with approximately 13,000 persons infected as of October 28, 2014. Before September 25, 2014, only four patients with Ebola had been treated in the United States; all of these patients had been diagnosed in West Africa and medically evacuated to the United States for care. |
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