Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Hughes SM

PROVIDER: S-EPMC7511692 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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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.

Hughes Sean M SM Levy Claire N CN Calienes Fernanda L FL Stekler Joanne D JD Pandey Urvashi U Vojtech Lucia L Berard Alicia R AR Birse Kenzie K Noël-Romas Laura L Richardson Brian B Golden Jackelyn B JB Cartwright Michael M Collier Ann C AC Stevens Claire E CE Curlin Marcel E ME Holtz Timothy H TH Mugo Nelly N Irungu Elizabeth E Katabira Elly E Muwonge Timothy T Lama Javier R JR Baeten Jared M JM Burgener Adam A Lingappa Jairam R JR McElrath M Juliana MJ Mackelprang Romel R McGowan Ian I Cranston Ross D RD Cameron Mark J MJ Hladik Florian F

Cell reports. Medicine 20200922 6

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 th ...[more]

PMID: 33015651

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Project description:BackgroundEcological communities tend to be spatially structured due to environmental gradients and/or spatially contagious processes such as growth, dispersion and species interactions. Data transformation followed by usage of algorithms such as Redundancy Analysis (RDA) is a fairly common approach in studies searching for spatial structure in ecological communities, despite recent suggestions advocating the use of Generalized Linear Models (GLMs). Here, we compared the performance of GLMs and RDA in describing spatial structure in ecological community composition data. We simulated realistic presence/absence data typical of many β-diversity studies. For model selection we used standard methods commonly used in most studies involving RDA and GLMs.MethodsWe simulated communities with known spatial structure, based on three real spatial community presence/absence datasets (one terrestrial, one marine and one freshwater). We used spatial eigenvectors as explanatory variables. We varied the number of non-zero coefficients of the spatial variables, and the spatial scales with which these coefficients were associated and then compared the performance of GLMs and RDA frameworks to correctly retrieve the spatial patterns contained in the simulated communities. We used two different methods for model selection, Forward Selection (FW) for RDA and the Akaike Information Criterion (AIC) for GLMs. The performance of each method was assessed by scoring overall accuracy as the proportion of variables whose inclusion/exclusion status was correct, and by distinguishing which kind of error was observed for each method. We also assessed whether errors in variable selection could affect the interpretation of spatial structure.ResultsOverall GLM with AIC-based model selection (GLM/AIC) performed better than RDA/FW in selecting spatial explanatory variables, although under some simulations the methods performed similarly. In general, RDA/FW performed unpredictably, often retaining too many explanatory variables and selecting variables associated with incorrect spatial scales. The spatial scale of the pattern had a negligible effect on GLM/AIC performance but consistently affected RDA's error rates under almost all scenarios.ConclusionWe encourage the use of GLM/AIC for studies searching for spatial drivers of species presence/absence patterns, since this framework outperformed RDA/FW in situations most likely to be found in natural communities. It is likely that such recommendations might extend to other types of explanatory variables.

Dataset Information

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

Publications

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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