排序方式: 共有88条查询结果,搜索用时 15 毫秒
1.
Angie S. Price Amy K. Nelson Alip Ghosh Shyamasundaran Kottilil Joel V. Chua 《Journal of medical virology》2023,95(1):e28105
Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log10 IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination. 相似文献
2.
Expression of chemokine and inhibitory receptors on natural killer cells: effect of immune activation and HIV viremia 总被引:4,自引:0,他引:4
Kottilil S Shin K Planta M McLaughlin M Hallahan CW Ghany M Chun TW Sneller MC Fauci AS 《The Journal of infectious diseases》2004,189(7):1193-1198
We examined the cell-surface expression of chemokine and natural killer (NK) cell inhibitory receptors (iNKRs) on NK cells from individuals with human immunodeficiency virus (HIV) infection, chronic hepatitis C infection, and Wegener's granulomatosis (WG), an inflammatory, granulomatous vasculitis. The expression of CCR5 on NK cells was up-regulated in individuals with HIV viremia and in individuals with active WG, indicating that expression of this receptor is modulated by states of immune activation associated with viral infection and inflammatory or immune-mediated diseases. In contrast, iNKRs were shown to be up-regulated only on NK cells of individuals with HIV viremia, and they returned to a normal level when viremia was controlled with effective antiviral therapy. In individuals with HIV-1 viremia, there was a direct correlation between the level of expression of p58.1, p58.2, and CD94 receptors and plasma HIV viremia, suggesting that ongoing active HIV replication has an effect on the expression of such receptors on NK cells. These results suggest that immune activation leads to abnormal cell-surface expression of chemokine receptors on NK cells, whereas HIV-specific processes account for the up-regulation of iNKRs on NK cells; this may explain the NK cell-functional defects seen in HIV infection. 相似文献
3.
Konstantin Chumakov Michael S. Avidan Christine S. Benn Stefano M. Bertozzi Lawrence Blatt Angela Y. Chang Dean T. Jamison Shabaana A. Khader Shyam Kottilil Mihai G. Netea Annie Sparrow Robert C. Gallo 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(21)
The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed “trained immunity.” An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to “bend the pandemic curve,” averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease. 相似文献
4.
Naggie S Osinusi A Katsounas A Lempicki R Herrmann E Thompson AJ Clark PJ Patel K Muir AJ McHutchison JG Schlaak JF Trippler M Shivakumar B Masur H Polis MA Kottilil S 《Hepatology (Baltimore, Md.)》2012,56(2):444-454
Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression. 相似文献
5.
Tess Petersen Kerry Townsend Lori A. Gordon Sreetha Sidharthan Rachel Silk Amy Nelson Chloe Gross Monica Calderón Michael Proschan Anu Osinusi Michael A. Polis Henry Masur Shyam Kottilil Anita Kohli 《Hepatology International》2016,10(2):310-319
Background
As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described.Methods
Medication adherence was measured in 60 HCV, genotype-1, treatment-naïve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report.Results
Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report.Conclusions
Adherence to short courses of DAA therapy with 1–3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.6.
Interferon stimulated exonuclease gene 20 kDa links psychiatric events to distinct hepatitis C virus responses in human immunodeficiency virus positive patients 下载免费PDF全文
7.
Neumann A Polis M Rozenberg L Jackson J Reitano K McLaughlin M Koratich C Dewar R Masur H Haagmans B Kottilil S 《AIDS (London, England)》2007,21(14):1855-1865
OBJECTIVE: The major antiviral effect of interferon (IFN)-alpha on hepatitis C virus (HCV) is blocking of virion production from infected cells. We now investigate the previously unknown mechanism of action of IFN-alpha against HIV. METHODS: HIV kinetics in parallel to HCV kinetics and IFN pharmacokinetics during pegylated-IFN-alpha-2b (1.5 microg/Kg q.w., PEG-IFN) and ribavirin (1-1.2 g daily) treatment in nine HIV patients co-infected with HCV genotype 1 were analyzed. In vivo modeling predictions of suppression of HIV replication by PEG-IFN in CD8-depleted peripheral blood mononuclear cells were verified by in vitro experiments. RESULTS: HCV and HIV show different viral decline patterns after administration of PEG-IFN. Unlike the bi-phasic decline shown by HCV, HIV shows a slow continuous decline during the first week, with no rebound when PEG-IFN levels decline. Fitting of HIV kinetics with known half-lives of free virus and infected cells indicates that the major effect of IFN on HIV is to block de novo infection rather than to block virion production. The magnitude of the antiviral effect is similar (mean 1.1 log10 decline at 7 days) to those of direct anti-HIV drugs, but shows an inverse correlation with baseline viremia. In vitro studies show that preincubation with IFN renders a suppression of HIV replication superior to that of treatment postinfection, thus corroborating the mathematical analysis in vivo. CONCLUSION: The complimentary antiviral properties of IFN-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of IFN as part of salvage therapy for HIV-infected individuals. 相似文献
8.
Erkin Musabaev Chris Estes Shakhlo Sadirova Shokhista Bakieva Krestina Brigida Rick Dunn Shyamasundaran Kottilil Poonam Mathur Ameer Abutaleb Kathryn Razavi-Shearer Tim Anstiss Bakhodir Yusupaliev Homie Razavi 《Liver international》2023,43(4):773-784
Background & Aims
Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large-scale simplified testing and treatment to implement a national viral hepatitis elimination program.Methods
Thirteen polyclinics were utilized to screen, conduct follow-up biochemical measures and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on-site. An electronic medical system tracked individuals through the cascade of care.Results
The use of rapid tests allowed for screening of 60 769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID-19 pandemic along with COVID testing. 13%–14% of individuals were lost to follow-up after the rapid test, and another 62%–66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment.Conclusions
The current study demonstrated the feasibility of large-scale general population screening and task shifting in low- and middle-income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment. 相似文献9.
Racial disparity in all‐cause mortality among hepatitis C virus‐infected individuals in a general US population,NHANES III 下载免费PDF全文
B. Emmanuel M. D. Shardell L. Tracy S. Kottilil S. S. El‐Kamary 《Journal of viral hepatitis》2017,24(5):380-388
There are few long‐term nationally representative studies of all‐cause mortality among those infected with hepatitis C virus (HCV). When an additional 5 years of data were made publicly available in 2015, the Third National Health and Nutrition Examination Survey Linked Mortality File became the longest nationally representative study in the United States. Our objective was to update the estimated HCV‐associated all‐cause mortality in the general US population and determine any differences by sex, age and race/ethnicity. HCV status was assessed in 9117 nationally representative adults aged 18‐59 years from 1988 to 1994, and mortality follow‐up of the same individuals was completed through 2011 and made publicly available in 2015. There were 930 deaths over a median follow‐up of 19.8 years. After adjusting for all covariate risk factors, chronic HCV had 2.63 times (95% CI: 1.59‐4.37; P=.0002) higher all‐cause mortality rate ratio (MRR) compared with being HCV negative. All‐cause MRR was stratified by sex, age and race/ethnicity. Only race/ethnicity was a significant effect modifier of MRR (P<.0001) as the highest MRR of chronic HCV compared to HCV negative was 7.48 (95% CI: 2.15‐26.10, P=.001) among Mexican Americans, 2.67 (95% CI: 2.67‐5.56, P=.009) among non‐Hispanic Whites and 2.02 (95% CI: 1.20‐3.40, P=.007) among non‐Hispanic Blacks. Racial disparity was seen in the all‐cause mortality as Mexican Americans with chronic HCV had approximately seven times higher mortality rate than HCV‐negative individuals. This suggests that these at‐risk individuals should be targeted for HCV screening and treatment, given the availability of new highly effective HCV therapies. 相似文献
10.
We describe the case of a patient with acquired immunodeficiency syndrome (AIDS) who had a CD4 cell count of 60/microL, bilateral hilar adenopathy, and hypercalcemia. Transbronchial biopsy showed T-cell anaplastic large cell lymphoma. Serology was negative for human T-cell leukemia virus-I (HTLV-I). This appears to be the first case of T-cell anaplastic large cell lymphoma occurring in an AIDS patient with hypercalcemia who was seronegative for HTLV-I. 相似文献