250 research outputs found
Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time.
No full textAbstract
BACKGROUND: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.
METHODOLOGY/PRINCIPAL FINDINGS: Included were 3763 treatment-change episodes (TCEs) for which a HIV-1 genotype was available at the time of changing treatment with at least one follow-up viral load measurement. Genotypic susceptibility scores for the active regimens were calculated using scores defined by each interpretation system. Using logistic regression, we determined the association between the genotypic susceptibility score and proportion of TCEs having an undetectable viral load (<50 copies/ml) at 12 (8-16) weeks (2152 TCEs), 24 (16-32) weeks (2570 TCEs), and 48 (44-52) weeks (1083 TCEs). The Area under the ROC curve was calculated using a 10-fold cross-validation to compare the different interpretation systems regarding the sensitivity and specificity for predicting undetectable viral load. The mean genotypic susceptibility score of the systems was slightly smaller for HIVdb, with 1.92+/-1.17, compared to Rega and ANRS, with 2.22+/-1.09 and 2.23+/-1.05, respectively. However, similar odds ratio's were found for the association between each-unit increase in genotypic susceptibility score and undetectable viral load at week 12; 1.6 [95% confidence interval 1.5-1.7] for HIVdb, 1.7 [1.5-1.8] for ANRS, and 1.7 [1.9-1.6] for Rega. Odds ratio's increased over time, but remained comparable (odds ratio's ranging between 1.9-2.1 at 24 weeks and 1.9-2.2 at 48 weeks). The Area under the curve of the ROC did not differ between the systems at all time points; p = 0.60 at week 12, p = 0.71 at week 24, and p = 0.97 at week 48.
CONCLUSIONS/SIGNIFICANCE: Three commonly used HIV drug resistance interpretation systems ANRS, Rega and HIVdb predict virological response at 12, 24, and 48 weeks, after change of treatment to the same extent
Evaluation and Optimization of an ELISA Procedure to Quantify Antibodies Against Pneumococcal Polysaccharides Included in the 13-Valent Conjugate Vaccine
No full textThe 13-valent pneumococcal conjugate vaccine (PCV-13) is recommended for HIV-infected people, although its effectiveness in this population remains under evaluation. In this study we describe the development, optimization and analytical validation of an ELISA procedure to measure specific antibodies for the pneumococcal polysaccharide serotypes included in PCV13 vaccine, testing sera obtained from HIV-infected outpatients (n=30) who received the vaccine. The protocol followed the last version of WHO guidelines, based on the new standard 007sp, with the modification of employing Statens Serum Institut (SSI) antigens. We supplied the assay performance validation in terms of sensitivity, reproducibility, precision and accuracy. In addition we detailed optimal antigen-coating concentrations and ELISA conditions common to all 13 serotypes, suitable for laboratories performing these assays in order to standardize the method. Our procedure showed reproducibility and reliability, making it a valid alternative for evaluating the response to pneumococcal serotypes included in PCV13 vaccine
The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma
No full textMelanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox)
HIV-1 non-R5 co-receptor tropism is associated with a larger size of the viral reservoir but not with a higher risk of virological rebound in patients on effective antiretroviral therapy
No full textIs there a drug-drug interaction between darunavir/ritonavir and raltegravir?
No full textNo Abstract availabl
Is there a drug-drug interaction between darunavir/ritonavir and raltegravir?
No full textNo Abstract availabl
Impact of 48 weeks of atazanavir/ritonavir plus lamivudine dual therapy on cellular HIV-DNA levels in the AtLaS pilot study
No full textnot availabl
Candida albicans as a Trailblazer for Herpes Simplex Virus-2 Infection Against an In Vitro Reconstituted Human Vaginal Epithelium
No full textLittle is known about the complex events driving host–pathogen and pathogen–pathogen interplay in polymicrobial infections. Using an in vitro model of a reconstituted vaginal epithelium (RVE) employing the A-431 cell line supplemented with synthetic vaginal fluid (SVF), we studied the consequences of single versus dual infections with Candida albicans and/or Herpes Simplex Virus-2 (HSV-2). Our data show (a) a relevant, SVF-enhanced expression of the differentiation marker cytokeratin 5/6 in the RVE; (b) the ability of Candida albicans to enhance HSV-2 in the dual infection model, with the virus titer almost doubling in the presence of SVF; (c) RVE damage (>20%), mostly attributable to Candida albicans and related to oxidative stress whether SVF is present; (d) the dysregulation of mucin-1, the production of which is enhanced (from 13 to 21 ng/mL) or impaired (from 21 to 10 ng/mL) in response to either SVF or infection, respectively; and (e) a partial-to-negligible cytokine response from the RVE, depending upon SVF presence. In conclusion, using an in vitro RVE model upgraded through the addition of synthetic vaginal fluid, we provide details on epithelial cell–pathogen–pathogen interaction, contributing to a better comprehension of the pathogenesis of polymicrobial infections at a mucosal level
Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study
No full textObjectives: AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir+lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up. Methods: At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA .50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL). Results: After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm3; P1/40.002) and Week 144 (+94 cells/mm3; P1/40.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P1/40.001), HDL cholesterol (+6 mg/dL; P1/40.024) and LDL cholesterol (+12 mg/dL; P1/40.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m2; P,0.001) and lumbar spine T-score and Z-score (+0.2, P1/40.011; and +0.35, P1/40.001, respectively) and a decrease in trunk fat (21.898 g; P1/40.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients. Conclusions: Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
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