Characterization of antigenic variants of hepatitis C virus in immune evasion

<p>Abstract</p> <p>Background</p> <p>Antigenic variation is an effective way by which viruses evade host immune defense leading to viral persistence. Little is known about the inhibitory mechanisms of viral variants on CD4 T cell functions.</p> <p>Results</p> <p>Using sythetic peptides of a HLA-DRB1*15-restricted CD4 epitope derived from the non-structural (NS) 3 protein of hepatitis C virus (HCV) and its antigenic variants and the peripheral blood mononuclear cells (PBMC) from six HLA-DRB1*15-positive patients chronically infected with HCV and 3 healthy subjects, the <it>in vitro </it>immune responses and the phenotypes of CD4⁺CD25⁺cells of chronic HCV infection were investigated. The variants resulting from single or double amino acid substitutions at the center of the core region of the Th1 peptide not only induce failed T cell activation but also simultaneously up-regulate inhibitory IL-10, CD25^-TGF-β⁺Th3 and CD4⁺IL-10⁺Tr1 cells. In contrast, other variants promote differentiation of CD25⁺TGF-β⁺Th3 suppressors that attenuate T cell proliferation.</p> <p>Conclusions</p> <p>Naturally occuring HCV antigenic mutants of a CD4 epitope can shift a protective peripheral Th1 immune response into an inhibitory Th3 and/or Tr1 response. The modulation of antigenic variants on CD4 response is efficient and extensive, and is likely critical in viral persistence in HCV infection.</p

Comparison of guideline concordant antibiotic prophylaxis in Veterans Affairs and non-Veterans Affairs dental settings among those with cardiac conditions or prosthetic joints

Abstract Background No research has been conducted to assess whether antibiotic prophylaxis prescribing differs by dental setting. Therefore, the goal of this study was to compare the prescribing of antibiotic prophylaxis in Veterans Affairs (VA) and non-Veterans Affairs settings. Methods This was a retrospective study of veteran and non-veteran dental patients with cardiac conditions or prosthetic joints between 2015–2017. Multivariable log binomial regression analysis was conducted to compare concordant prescribing by setting with a sub-analysis for errors of dosing based on antibiotic duration (i.e., days prescribed). Results A total of 61,124 dental visits that received a prophylactic antibiotic were included. Most were male (61.0%), and 55 years of age or older (76.2%). Nearly a third (32.7%) received guideline concordant prophylaxis. VA dental settings had a lower prevalence of guideline concordant prescribing compared to non-VA settings in unadjusted results (unadjusted prevalence ratio [uPR] = 0.92, 95% CI: 0.90–0.95). After adjustment, prevalence of guideline concordant prescribing was higher in those with prosthetic joints in the VA setting (adjusted prevalence ratio [aPR] = 1.73, 95% CI: 1.59–1.88), with no difference identified in those without a prosthetic joint (aPR = 0.99, 95% CI: 0.96–1.01). Concordance of dosing was higher in VA compared to non-VA settings (aPR = 1.11, 95% CI: 1.07–1.15). Conclusions VA has a higher prevalence of guideline concordant prescribing among those with prosthetic joints and when assessing dosing errors. Though the presence of an integrated electronic health record (EHR) may be contributing to these differences, other system or prescriber-related factors may be responsible. Future studies should focus on to what extent the integrated EHR may be responsible for increased guideline concordant prescribing in the VA setting

Changes in Body Mass Index Following HAART Initiation among HIV Infected Women in the Women’s Interagency HIV Study

Examine changes in, and factors associated with changing body mass index (BMI) in women following highly active antiretroviral therapy (HAART) initiation. 1177 HIV-infected Women's Interagency HIV Study participants who contributed 10,754 years of follow-up following HAART initiation were studied. Changes in median BMI up to 15 years following HAART initiation, and the highest and lowest BMI reached following HAART initiation were summarized by pre-HAART BMI category (&lt;18.5 [underweight], 18.5-&lt;25.0 [normal weight], 25.0-&lt;30.0 [overweight], 30.0-&lt;40.0 [obese], and ≥ 40.0 [morbidly obese]). Multivariate mixed effects ordinal logistic regression estimated the degree of association of each exposure of interest with post-HAART BMI. Before HAART, 39% percent of women had normal BMI, 31% were overweight, 23% were obese, and 5% were morbidly obese. Following HAART initiation, median BMI change (per 5 years) was 0.21 kg/m2 (90% confidence interval [CI]: -1.33, 0.42) for those with normal pre-HAART BMI, 0.39 kg/m2 (90% CI: 0.15,0.66) for overweight, 0.31 kg/m2 (90% CI: -1.18,0.67) for obese, and -0.36kg/m2 for morbidly obese women. After initiating HAART, 40% with normal pre-HAART BMI became overweight at some point; of those overweight, 46% remained overweight and 47% became obese; 71% of obese women remained obese and 27% became morbidly obese. Each year of nucleoside analog reverse transcriptase inhibitor use was associated with a 3% decreased odds of reaching a higher BMI category (OR 0.97, 95% CI: 0.95, 0.99), while each year of protease inhibitor or non-nucleoside analog reverse transcriptase inhibitor use were associated with a 6% (OR 1.06, 95% CI: 1.04, 1.08) and 5%(OR 1.05, 95% CI: 1.01, 1.08) increased odds of having a higher BMI category, respectively. Although overweight and obesity are highly prevalent in this large cohort of HIV-infected, minority women, HAART use was associated with only a modest increase in BMI over time

Prevalence and Correlates of Elevated Body Mass Index among HIV-Positive and HIV-Negative Women in the Women's Interagency HIV Study

Since the introduction of highly active antiretroviral therapy (HAART) and the subsequent increased life expectancy in HIV-infected persons, non-HIV–related diseases have become an important cause of morbidity and mortality. This cross-sectional study reports the prevalence of overweight and obesity, and sociodemographic, psychological, and substance use-related risk factors for elevated body mass index (BMI) among 2157 HIV-seropositive (HIV+) in comparison to 730 HIV-seronegative (HIV−) participants in the Women's Interagency HIV Study (WIHS). Separate univariable and multivariate linear regression analyses were completed for HIV+ and HIV− women. Our study revealed a similar proportion of obesity (body mass index [BMI] ≥30) among HIV+ (33%) and HIV− women (29%) (p = 0.12), as well as comparable median BMI (HIV+: 26.1 versus HIV−: 26.7, p = 0.16). HIV+ compared to HIV− women, respectively, were significantly (p < 0.01) older (median = 35.6 versus. 32.5), but similar (p = 0.97) by race/ethnicity (57% African American, 28% Hispanic, and 15% white for both). In multivariate models for both HIV+ and HIV− women, African American race/ethnicity was significantly (p < 0.05) associated with higher BMI, while higher quality of life score and illicit hard drug use were associated with lower BMI. Additionally, smoking, alcohol use, markers of advanced HIV infection (AIDS diagnosis, elevated HIV viral load, low CD4 count), and a history of antiretroviral therapy use (ART) were also associated with lower BMI among HIV+ women. In conclusion, risk factors for elevated BMI were similar for HIV+ and HIV− women in the WIHS. For HIV+ women, all markers of advanced HIV infection and ART use were additionally associated with lower BMI