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Cover -- Half Title -- Series Page -- Title Page -- Copyright Page -- Contents -- Acknowledgments -- Abbreviations of Works by Aristotle -- Introduction -- Part I: The Logos of Logos -- Chapter 1: Language, Logic, and Metaphysics: The Being with Logos and the Logos of Being -- Part II: The Logos of Phusis -- Chapter 2: "For There Are Gods Here Too": Embodied Essence, Two-Footedness, and the Animal with Logos -- Chapter 3: The Significance of Self-Nourishment: Aristotle's De Anima II.4 -- Chapter 4: Flesh as Logos -- Chapter 5: Perception, Thought, and Error in Aristotle's De Anima -- Chapter 6: "Actuality in the First Sense" and the Question of Human Nature in Aristotle -- Part III: The Logos of Ethos -- Chapter 7: Wishful Thinking in Aristotle -- Chapter 8: The Dissociative Power of Logos in Taking Account of Oneself -- Chapter 9: Aristotle on the Rationality of Virtue -- Chapter 10: Learning How to Be at Leisure through Musical Education -- Part IV: The Logos of the Polis -- Chapter 11: The Vicissitudes of Logos: On Nature, Character, and Time-of-Life -- Chapter 12: Practical Logos in Aristotle's Ethics, Rhetoric, and Politics -- Chapter 13: The Movement of Political Animals -- Chapter 14: Aristotle: The Politics of Life and the Life of Politics -- Chapter 15: Logos and the Polis in the Poetics -- Bibliography -- Contributors -- Index.

BackgroundInjection drug users (IDUs) face numerous obstacles to receiving optimal HIV care, and have been shown to underutilize antiretroviral therapy (ART). We sought to estimate the degree to which providers of HIV care defer initiation of ART because of injection drug use and to identify clinic and provider‐level factors associated with resistance to prescribing ART to IDUs.MethodsWe administered an Internet‐based survey to 662 regular prescribers of ART in the United States and Canada. Questionnaire items assessed characteristics of providers' personal demographics and training, site of clinical practice and attitudes about drug use. Respondents then rated whether they would likely prescribe or defer ART for hypothetical patients in a series of scenarios involving varying levels of drug use and HIV disease stage.ResultsSurvey responses were received from 43% of providers invited by email and direct mail, and 8.5% of providers invited by direct mail only. Overall, 24.2% of providers reported that they would defer ART for an HIV‐infected patient with a CD4+ cell count of 200 cells/mm3 if the patient actively injected drugs, and 52.4% would defer ART if the patient injected daily. Physicians were more likely than non‐physician providers to defer ART if a patient injected drugs (adjusted odds ratio 2.6, 95% CI 1.4‐4.9). Other predictors of deferring ART for active IDUs were having fewer years of experience in HIV care, regularly caring for fewer than 20 HIV‐infected patients, and working at a clinic serving a population with low prevalence of injection drug use. Likelihood of deferring ART was directly proportional to both CD4+ cell count and increased frequency of injecting.ConclusionsMany providers of HIV care defer initiation of antiretroviral therapy for patients who inject drugs, even in the setting of advanced immunologic suppression. Providers with more experience of treating HIV, those in high injection drug use prevalence areas and non‐physician providers may be more willing to prescribe ART despite on‐going injection drug use. Because of limitations, including low response rate and use of a convenience sample, these findings may not be generalizable to all HIV care providers in North America.

AbstractIntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD).MethodsAdult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

Altres ajuts: This work was funded by grants from the National Institutes of Health (RO1AI46995 to P.G.) and the Wellcome Trust (WT104748MA to P.G.). This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E (to M.C.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042 (Johns Hopkins University Bloomberg School of Public Health; Joseph Margolick, rincipal investigator [PI]), U01-AI35039 (Northwestern University; Steven Wolinsky, PI), U01-AI35040 (University of California, Los Angeles; Roger Detels and Oto Martinez, multiple principal investigators [MPI]), U01-AI35041 (University of Pittsburgh; Charles Rinaldo, PI), and UM1-AI35043 (Johns Hopkins University Bloomberg School of Public Health; Lisa Jacobson, PI). The SCOPE cohort was supported by the UCSF/Gladstone Institute of Virology and Immunology CFAR (P30 AI027763) and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109 and A127966) and the amfAR Institute for HIV Cure Research (amfAR 109301). P.B. is a Jenner Investigator. I.W. and P.P. are funded by MRC Programme grant MR/K012037. ; The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8 + T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8 + T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8 + T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8 + T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8 + T-cell responses that dominate HIV-specific CD8 + T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV. IMPORTANCE CD8 + T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8 + T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8 + T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8 + T-cell activity in HLA-B*27:05-positive subjects.