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

Hepatitis B Stigma and Knowledge among Vietnamese in Ho Chi Minh City and Chicago

Stigma regarding viral hepatitis and liver disease has psychological and social consequences including causing negative self-image, disrupting relationships, and providing a barrier to prevention, testing, and treatment. The aim of this study was to characterize and compare HBV knowledge and stigma in Vietnamese in Ho Chi Minh City and Chicago and to begin to evaluate the cultural context of HBV stigma. Methods. A written survey including knowledge questions and a validated HBV stigma questionnaire was distributed to Vietnamese in Ho Chi Minh City and Chicago. 842 surveys from Ho Chi Minh City and 170 from Chicago were analyzed. Results. Vietnamese living in Chicago had better understanding of HBV transmission and that HBV can cause chronic infection and liver cancer. Vietnamese in Chicago had higher stigma scores on a broad range of items including guilt and shame about HBV and were more likely to feel that persons with HBV can bring harm to others and should be isolated. Conclusions. Vietnamese in Ho Chi Minh City and Chicago have knowledge deficits about HBV, particularly regarding modes of transmission. Persons in Ho Chi Minh City expressed lower levels of HBV stigma than Vietnamese living in Chicago, likely reflecting changing cultural attitudes in Vietnam. Culturally appropriate educational initiatives are needed to address the problem of HBV stigma

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