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Sample records for point viral loads

  1. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

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    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  2. Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load.

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    Samuel Alizon

    Full Text Available HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.

  3. SAMBA HIV semiquantitative test, a new point-of-care viral-load-monitoring assay for resource-limited settings.

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    Ritchie, Allyson V; Ushiro-Lumb, Ines; Edemaga, Daniel; Joshi, Hrishikesh A; De Ruiter, Annemiek; Szumilin, Elisabeth; Jendrulek, Isabelle; McGuire, Megan; Goel, Neha; Sharma, Pia I; Allain, Jean-Pierre; Lee, Helen H

    2014-09-01

    Routine viral-load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA semi-Q (simple amplification-based assay semiquantitative test for HIV-1) in London, Malawi, and Uganda. The SAMBA semi-Q can distinguish between patients with VLs above and below 1,000 copies/ml. The SAMBA semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test, v2.0. Testing of 96 2- to 10-fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda yielded an overall accuracy for the SAMBA semi-Q of 99% (95% confidence interval [CI], 93.8 to 99.9%) and 96.9% (95% CI 94.9 to 98.3%), respectively, compared to to the Roche test. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cutoff of 1,000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral loads of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control, defined as either SAMBA cutoff) or SAMBA semi-Q has adequate concurrency with the gold standard measurements for viral load. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings. Copyright © 2014 Ritchie et al.

  4. Leukodepletion as a Point-of-Care Method for Monitoring HIV-1 Viral Load in Whole Blood

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    Titchmarsh, Logan; Zeh, Clement; Verpoort, Thierry; Allain, Jean-Pierre

    2014-01-01

    In order to limit the interference of HIV-1 cellular nucleic acids in estimating viral load (VL), the feasibility of leukodepletion of a small whole-blood (WB) volume to eliminate only leukocyte cell content was investigated, using a selection of filters. The efficacy of leukocyte filtration was evaluated by counting, CD45 quantitative PCR, and HIV-1 DNA quantification. Plasma HIV-1 was tested by real-time reverse transcription (RT)-PCR. A specific, miniaturized filter was developed and tested for leukocyte and plasma virus retention, WB sample dilution, and filtration parameters in HIV-1-spiked WB samples. This device proved effective to retain >99.9% of white blood cells in 100 μl of WB without affecting plasma VL. The Samba sample preparation chemistry was adapted to use a leukodepleted WB sample for VL monitoring using the point-of-care Samba-1 semiautomated system. The clinical performance of the assay was evaluated by testing 207 consecutive venous EDTA WB samples from HIV-1-infected patients attending a CD4 testing clinic. Most patients were on antiretroviral treatment (ART), but their VL status was unknown. Compared to the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test, the new Samba assay had a concordance of 96.5%. The use of the Samba system with a VL test for WB might contribute to HIV-1 ART management and reduce loss-to-follow-up rates in resource-limited settings. PMID:25428162

  5. Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study.

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    Grebely, Jason; Lamoury, Francois M J; Hajarizadeh, Behzad; Mowat, Yasmin; Marshall, Alison D; Bajis, Sahar; Marks, Philippa; Amin, Janaki; Smith, Julie; Edwards, Michael; Gorton, Carla; Ezard, Nadine; Persing, David; Kleman, Marika; Cunningham, Philip; Catlett, Beth; Dore, Gregory J; Applegate, Tanya L

    2017-07-01

    Point-of-care hepatitis C virus (HCV) RNA testing offers an advantage over antibody testing (which only indicates previous exposure), enabling diagnosis of active infection in a single visit. In this study, we evaluated the performance of the Xpert HCV Viral Load assay with venepuncture and finger-stick capillary whole-blood samples. Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort enrolled at five sites in Australia (three drug and alcohol clinics, one homelessness service, and one needle and syringe programme). We compared the sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection by venepuncture and finger-stick collection with the Abbott RealTime HCV Viral Load assay (gold standard). Of 210 participants enrolled between Feb 8, 2016, and July 27, 2016, 150 participants had viral load testing results for the three assays tested. HCV RNA was detected in 45 (30% [95% CI 23-38]) of 150 participants based on Abbott RealTime. Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in plasma collected by venepuncture was 100·0% (95% CI 92·0-100·0) and specificity was 99·1% (95% CI 94·9-100·0). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick was 95·5% (95% CI 84·5-99·4) and specificity was 98·1% (95% CI 93·4-99·8). No adverse events caused by the index test or the reference standard were observed. The Xpert HCV Viral Load test can detect active infection from a finger-stick sample, which represents an advance over antibody-based tests that only indicate past or previous exposure. National Health and Medical Research Council (Australia), Cepheid, South Eastern Sydney Local Health District (Australia), and Merck Sharp & Dohme (Australia). Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Performance of the SAMBA I and II HIV-1 Semi-Q Tests for viral load monitoring at the point-of-care.

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    Goel, Neha; Ritchie, Allyson V; Mtapuri-Zinyowera, Sekesai; Zeh, Clement; Stepchenkova, Tetiana; Lehga, Jesse; De Ruiter, Annemiek; Farleigh, Laura E; Edemaga, Daniel; So, Rosario; Sembongi, Hiroshi; Wisniewski, Craig; Nadala, Lourdes; Schito, Marco; Lee, Helen

    2017-06-01

    Although access to antiretroviral therapy for HIV infection is increasing in resource-poor countries, viral load testing for monitoring of treatment efficacy remains limited, expensive, and confined to centralized laboratories. The SAMBA HIV-1 Semi-Q Test is a nucleic acid-based amplification assay developed for viral load monitoring performed on either the semi-automated SAMBA I system for laboratory use or the fully automated SAMBA II system for point-of care use. We have assessed the performance characteristics of the SAMBA HIV-1 Semi-Q Test on SAMBA I and SAMBA II systems according to the Common Technical Specifications of the European Community's 98/79 In Vitro Diagnostic Medical Devices Directive. The sensitivity, specificity, reproducibility, and viral subtype coverage of the test were similar on the SAMBA I and SAMBA II platforms. The clinical performance on the SAMBA I system was compared with the Roche CAP/CTM assay and evaluated in-house with 130 patient specimens from London as well as in the field with 390 specimens in Kenya and Zimbabwe. The overall concordance between the SAMBA and CAP/CTM assays was 98.1%. The clinical performance of the test on the SAMBA II platform in comparison with the Abbott HIV-1 RealTime Assay was evaluated in-house with 150 specimens from Ukraine, yielding a concordance of 98.0%. The results thus show that the SAMBA HIV-1 Semi-Q Test performs equivalently on SAMBA I and SAMBA II, and they suggest that the test is suitable for implementation at the point-of-care in resource-poor regions where viral load testing is desperately needed but often unavailable. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. HIV community viral load trends in South Carolina.

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    Chakraborty, Hrishikesh; Weissman, Sharon; Duffus, Wayne A; Hossain, Akhtar; Varma Samantapudi, Ashok; Iyer, Medha; Albrecht, Helmut

    2017-03-01

    Community viral load is an aggregate measure of HIV viral load in a particular geographic location, community, or subgroup. Community viral load provides a measure of disease burden in a community and community transmission risk. This study aims to examine community viral load trend in South Carolina and identify differences in community viral load trends between selected population subgroups using a state-wide surveillance dataset that maintains electronic records of all HIV viral load measurements reported to the state health department. Community viral load trends were examined using random mixed effects models, adjusting for age, race, gender, residence, CD4 counts, HIV risk group, and initial antiretroviral regimen during the study period, and time. The community viral load gradually decreased from 2004 to 2013 ( p HIV risk group, and single-tablet regimen versus multiple-tablet regimen subgroups. Slower declines in community viral load among females, those in rural areas, and heterosexuals suggest possible disparities in care that require further exploration. The association between using single-tablet regimen and faster community viral load decline is noteworthy.

  8. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Directory of Open Access Journals (Sweden)

    Joshua T Herbeck

    2014-06-01

    Full Text Available Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  9. Gender difference in HIV-1 RNA viral loads

    NARCIS (Netherlands)

    Donnelly, C. A.; Bartley, L. M.; Ghani, A. C.; Le Fevre, A. M.; Kwong, G. P.; Cowling, B. J.; van Sighem, A. I.; de Wolf, F.; Rode, R. A.; Anderson, R. M.

    2005-01-01

    To test and characterize the dependence of viral load on gender in different countries and racial groups as a function of CD4 T-cell count. Plasma viral load data were analysed for > 30,000 HIV-infected patients attending clinics in the USA [HIV Insight (Cerner Corporation, Vienna, VA, USA) and Plum

  10. Comparison of HIV-1 viral loads and effects of praziquantel ...

    African Journals Online (AJOL)

    Dr Humphrey

    Abstract. Background: It is hypothesised that Th2 immunological environment associated with Schistosoma mansoni infection might favour replication of HIV-1 in co-infected individuals, results in increased viral loads. On the other hand, deworming using praziquantel might result in reduction of HIV-1 viral loads and ...

  11. Short Report Challenges with targeted viral load testing for medical ...

    African Journals Online (AJOL)

    Challenges with targeted viral load testing 179. Malawi Medical ... targeted viral load (VL) testing for patients who have been on ART for at least .... Tuberculosis. 32. Community-acquired pneumonia. 17. Non-typhoidal Salmonella sepsis. 5. Bacterial meningitis. 5. Disseminated Kaposi sarcoma. 4. Cryptococcal meningitis. 4.

  12. Experience with Hepatitis B viral load testing in Nigeria | Okwuraiwe ...

    African Journals Online (AJOL)

    Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV DNA levels, ...

  13. 101 . experience with hepatitis b viral load testing in nigeria

    African Journals Online (AJOL)

    User

    ABSTRACT. Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus. (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV ...

  14. HIV-1 viral diversity and its implications for viral load testing: review of current platforms.

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    Luft, LeeAnne M; Gill, M John; Church, Deirdre L

    2011-10-01

    The 2008 Recommendations for care of the International AIDS Society reaffirmed the importance of both accurate and sensitive viral load assessment, and by necessity, access to viral load assays. HIV-1 viral load testing is considered essential when initiating antiretroviral therapy (ART), when monitoring ART response, and when considering switching ART regimens. The demand for accurate, reproducible, and cost-effective viral load assays is therefore a global issue. Although the North American and Western European experience has historically been with HIV-1 group M subtype B virus, this paradigm is changing rapidly as migrants and refugees from developing countries with non-B subtype infections often now present for care in the developed world, and travelers to developing countries acquire non-B subtype infection abroad and present for care at home. Awareness of any clinical or laboratory differences between the common HIV-1 group M subtype B and the newer HIV-1 strains being seen in practice is therefore increasingly important. This review of current HIV-1 viral load testing is focused on the potential value of a standardized genotype assignment for HIV-1 viral subtypes, regular monitoring of the performance of available commercial HIV viral load assays on emerging non-B HIV subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs), and a discussion of the implications for resource-limited settings. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. Tissue viral load variability in chronic hepatitis C.

    LENUS (Irish Health Repository)

    Fanning, L

    2012-02-03

    OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

  16. Piecewise mixed-effects models with skew distributions for evaluating viral load changes: A Bayesian approach.

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    Huang, Yangxin; Dagne, Getachew A; Zhou, Shumin; Wang, Zhongjun

    2015-12-01

    Studies of human immunodeficiency virus dynamics in acquired immuno deficiency syndrome (AIDS) research are very important in evaluating the effectiveness of antiretroviral (ARV) therapies. The potency of ARV agents in AIDS clinical trials can be assessed on the basis of a viral response such as viral decay rate or viral load change in plasma. Following ARV treatment, the profile of each subject's viral load tends to follow a 'broken stick'-like dynamic trajectory, indicating multiple phases of decline and increase in viral loads. Such multiple-phases (change-points) can be described by a random change-point model with random subject-specific parameters. One usually assumes a normal distribution for model error. However, this assumption may be unrealistic, obscuring important features of within- and among-subject variations. In this article, we propose piecewise linear mixed-effects models with skew-elliptical distributions to describe the time trend of a response variable under a Bayesian framework. This methodology can be widely applied to real problems for longitudinal studies. A real data analysis, using viral load data from an AIDS study, is carried out to illustrate the proposed method by comparing various candidate models. Biologically important findings are reported, and these findings also suggest that it is very important to assume a model with skew distribution in order to achieve reliable results, in particular, when the data exhibit skewness. © The Author(s) 2011.

  17. Examining HIV Viral Load in a Matched Cohort of HIV Positive Individuals With and Without Psoriasis.

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    Wu, Jashin J; Gilbert, Kathleen E; Batech, Michael; Manalo, Iviensan F; Towner, William J; Raposo, Rui André Saraiva; Nixon, Douglas F; Liao, Wilson

    2017-04-01

    BACKGROUND: HIV-associated psoriasis is well-documented. Genetic, cellular, and cytokine profiles have been used as evidence to suggest psoriasis activates antiviral pathways. There has been a lack of epidemiologic evidence investigating whether psoriasis patients have lower HIV viral counts compared to non-psoriasis patients. OBJECTIVE: Compare the viral load set point of HIV positive patients with and without psoriasis. METHODS: A retrospective matched cohort study of HIV positive patients with and without psoriasis using the Kaiser Permanente Southern California Health Plan database. RESULTS: We identified 101 HIV-positive psoriasis cases; 19 met inclusion criteria and were matched with 3-5 control patients; 94 total patients were analyzed. The mean age was 41.4 (12.07) years and 83% were male. Overall, the median log of the viral load of cases was slightly higher than controls (4.3 vs 4.2; P less than 0.01). CONCLUSIONS: The serum viral load set point of patients with HIV and psoriasis was slightly higher than the viral load set point of HIV patients without psoriasis. J Drugs Dermatol. 2017;16(4):372-377..

  18. Hepatitis C virus genotypes: A plausible association with viral loads

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    Salma Ghulam Nabi

    2013-01-01

    Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.

  19. Challenges with targeted viral load testing for medical inpatients at ...

    African Journals Online (AJOL)

    Background Approximately 75% of medical inpatients at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi are HIV seropositive, and a third of these patients are on antiretroviral therapy (ART). Malawi guidelines recommend targeted viral load (VL) testing for patients on ART for at least one year who report ...

  20. Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

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    Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J

    2017-08-01

    Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

  1. Use of reverse-transcriptase-based HIV-1 viral load assessment to confirm low viral loads in newly diagnosed patients in Switzerland.

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    Vetter, Beatrice N; Shah, Cyril; Huder, Jon B; Böni, Jürg; Schüpbach, Jörg

    2014-02-13

    Treatment-naïve patients newly diagnosed with HIV occasionally present with low viral RNA of ≤1'000 copies/ml, raising concerns about viral load underestimation. Because falsely low or undetectable viral loads might lead to inadvertent virus transmission or treatment delays, confirmation of such cases by a sequence-independent viral load test is recommended in Switzerland. HIV-1 RNA ≤1'000 cp/ml by Roche's or Abbott's tests in patients newly diagnosed from 2010 to 2012 in Switzerland were subjected to viral load testing by the product-enhanced-reverse transcriptase (PERT) assay. These investigations were complemented with repeat and/or alternative viral RNA measurements. HIV-1 RNA ≤1'000 cp/ml was observed in 71 of 1814 newly diagnosed patients. The PERT assay suggested clinically relevant viral load underestimation in 7 of 32 cases that could be investigated. In four patients, the PERT viral load was 10-1'000-fold higher; this was confirmed by alternative HIV-1 RNA tests. Six of the 7 underestimates had been obtained with meanwhile outdated versions of Roche's HIV-1 RNA test. In the seventh patient, follow-up revealed similar results for RNA and PERT based viral loads. PERT assay revealed occasional severe viral load underestimation by versions of HIV-1 RNA tests meanwhile outdated. Underestimation by contemporary tests appears rare, however.

  2. TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients

    DEFF Research Database (Denmark)

    Madsen, Chris; Eugen-Olsen, Jesper; Kirk, Ole

    2002-01-01

    PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included...... polymorphisms (RFLPs) and sequencing. RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p =.0001), a significant...... reduction in TTV viral load (p =.0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing...

  3. Impact of Chloroquine on Viral Load in Breast Milk

    Science.gov (United States)

    Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

    2006-01-01

    Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

  4. Diagnosing norovirus-associated infectious intestinal disease using viral load

    Directory of Open Access Journals (Sweden)

    Tam Clarence C

    2009-05-01

    Full Text Available Abstract Background Reverse transcription-polymerase chain reaction (RT-PCR is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID. However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case. Methods Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases. Results One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories. Conclusion We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to

  5. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    Science.gov (United States)

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  6. Cytomegalovirus blood viral load and hearing loss in young children with congenital infection.

    Science.gov (United States)

    Ross, Shannon A; Novak, Zdenek; Fowler, Karen B; Arora, Nitin; Britt, William J; Boppana, Suresh B

    2009-07-01

    This study was designed to determine whether elevated viral load in infants and young children is associated with congenital cytomegalovirus (CMV)-related hearing loss. Blood samples were obtained from 135 children with congenital CMV infection. CMV DNA in the peripheral blood was quantitated with a real-time polymerase chain reaction assay. Viral load measurements were analyzed in 3 different age groups (load >3500 genomic equivalents per milliliter (ge/mL) at load load is not associated with hearing loss in children with congenital CMV infection. However, a viral load of loss in children born with asymptomatic congenital infection.

  7. Herpesviruses viral loads and levels of proinflammatory cytokines in apical periodontitis.

    Science.gov (United States)

    Jakovljevic, A; Knezevic, A; Nikolic, N; Soldatovic, I; Jovanovic, T; Milasin, J; Andric, M

    2018-01-09

    This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines. A total of 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR. The concentrations of TNF-α, IL-1β and IL-6 were determined by ELISA method. SPSS software was used for statistical analysis. There were no significant differences in the occurrence of EBV and HCMV between symptomatic and asymptomatic periapical lesions (p = .686, p = .879, respectively). Only 12 of 74 EBV (16.2%) and four of 54 HCMV (13.5%) nested PCR-positive samples showed increased viral copy numbers above the limit of 125 copies/ml. There was no significant correlation between the levels of analysed proinflammatory cytokines and herpesviral copy numbers in our sample. The observed low viral loads point to a relatively rare occurrence of active EBV and HCMV infection in our sample. Latent herpesviral infection does not enhance the production of investigated proinflammatory cytokines. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  8. Community-driven demand creation for the use of routine viral load testing: a model to scale up routine viral load testing.

    Science.gov (United States)

    Killingo, Bactrin M; Taro, Trisa B; Mosime, Wame N

    2017-11-01

    HIV treatment outcomes are dependent on the use of viral load measurement. Despite global and national guidelines recommending the use of routine viral load testing, these policies alone have not translated into widespread implementation or sufficiently increased access for people living with HIV (PLHIV). Civil society and communities of PLHIV recognize the need to close this gap and to enable the scale up of routine viral load testing. The International Treatment Preparedness Coalition (ITPC) developed an approach to community-led demand creation for the use of routine viral load testing. Using this Community Demand Creation Model, implementers follow a step-wise process to capacitate and empower communities to address their most pressing needs. This includes utlizing a specific toolkit that includes conducting a baseline assessment, developing a treatment education toolkit, organizing mobilization workshops for knowledge building, provision of small grants to support advocacy work and conducting benchmark evaluations. The Community Demand Creation Model to increase demand for routine viral load testing services by PLHIV has been delivered in diverse contexts including in the sub-Saharan African, Asian, Latin American and the Caribbean regions. Between December 2015 and December 2016, ITPC trained more than 240 PLHIV activists, and disbursed US$90,000 to network partners in support of their national advocacy work. The latter efforts informed a regional, community-driven campaign calling for domestic investment in the expeditious implementation of national viral load testing guidelines. HIV treatment education and community mobilization are critical components of demand creation for access to optimal HIV treatment, especially for the use of routine viral load testing. ITPC's Community Demand Creation Model offers a novel approach to achieving this goal. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of

  9. Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

    Science.gov (United States)

    Fu, Wei; Park, Daniel E.; Shi, Qiyuan; Higdon, Melissa M.; Baggett, Henry C.; Brooks, W. Abdullah; Deloria Knoll, Maria; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Scott, J. Anthony G.; Thea, Donald M.; Adrian, Peter V.; Antonio, Martin; Awori, Juliet O.; Baillie, Vicky L.; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Goswami, Doli; Karron, Ruth A.; Li, Mengying; Morpeth, Susan C.; Mwaba, John; Mwansa, James; Prosperi, Christine; Sawatwong, Pongpun; Sow, Samba O.; Tapia, Milagritos D.; Whistler, Toni; Zaman, Khalequ; Zeger, Scott L.; O’ Brien, Katherine L.; Murdoch, David R.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Mahomed, Nasreen; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne

    2017-01-01

    Abstract Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia. PMID:28575373

  10. Improving laboratory efficiencies to scale-up HIV viral load testing.

    Science.gov (United States)

    Alemnji, George; Onyebujoh, Philip; Nkengasong, John N

    2017-03-01

    Viral load measurement is a key indicator that determines patients' response to treatment and risk for disease progression. Efforts are ongoing in different countries to scale-up access to viral load testing to meet the Joint United Nations Programme on HIV and AIDS target of achieving 90% viral suppression among HIV-infected patients receiving antiretroviral therapy. However, the impact of these initiatives may be challenged by increased inefficiencies along the viral load testing spectrum. This will translate to increased costs and ineffectiveness of scale-up approaches. This review describes different parameters that could be addressed across the viral load testing spectrum aimed at improving efficiencies and utilizing test results for patient management. Though progress is being made in some countries to scale-up viral load, many others still face numerous challenges that may affect scale-up efficiencies: weak demand creation, ineffective supply chain management systems; poor specimen referral systems; inadequate data and quality management systems; and weak laboratory-clinical interface leading to diminished uptake of test results. In scaling up access to viral load testing, there should be a renewed focus to address efficiencies across the entire spectrum, including factors related to access, uptake, and impact of test results.

  11. DNA-guided hepatitis B treatment: Viral load is insufficient with few exceptions

    OpenAIRE

    Jain, Pankaj

    2009-01-01

    In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule: a residual level hepatitis B virus (HBV) DNA at 24 wk predicts beneficial outcome and reduced resistance at 1 year. The genotypic viral resistance to antiviral agents and occu...

  12. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

    Directory of Open Access Journals (Sweden)

    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  13. Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months

    DEFF Research Database (Denmark)

    Katzenstein, T L; Ullum, H; Røge, Birgit T

    2003-01-01

    OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of HIV-RNA copies/mL. METHODS: A prospective study of one hundred and three patients......-one per cent had plasma viral load of /= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (Ig......A) differed significantly between the plasma viral load rebound groups (P HIV-DNA...

  14. Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

    Science.gov (United States)

    Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang

    2018-03-01

    Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Viral Load Pattern Among Hepatitis B Surface Antigen‑positive ...

    African Journals Online (AJOL)

    2015-03-13

    Mar 13, 2015 ... Abstract. Background: Hepatitis B viral infection is an old medical problem with worldwide distribution. It is usually diagnosed using serologic methods. However, the decision as to which patient to treat or not remains challenging due to the poor sensitivity of serologic markers as prognostic or severity ...

  16. HPV infection, risk factors and viral load among Mexican male college students.

    Science.gov (United States)

    Vera-Uehara, Carmina; Sánchez-Alemán, Miguel Angel; Uribe-Salas, Felipe Javier; Ramos-Castañeda, José; Olamendi-Portugal, Ma Leónidez; Conde-Glez, Carlos Jesús

    2014-01-01

    To determine the prevalence of HPV and the risky sexual behaviors associated to it in a sample of male college students, taking into account genotype and viral load. From 2002 to 2003, male students from the Autonomous University of Morelos State completed a questionnaire and provided self-collected genital samples to detect and quantify HPV. We performed a bivariate and a multivariate logistic regression analysis to identify correlates associated with the infection and to assess the viral load as a function of the viral infecting type. The fragments of β-globin gene and L1 of HPV, were amplified, purified and cloned, to evaluate viral load. Among 253 subjects, HPV prevalence was 19.4%, and HPV16 was the most common subtype. History of STIs (OR=4.8; 95% CI 1.2-18.9), contraceptive pill use by female partner (OR=2.6; 95% CI 1.1-6.3) and exchanging sex for money (OR=4.9; 95% CI 1.2-20) were associated to the HPV infection. HPV16 viral load was 7.8 copies (HPV/beta-globin) compared to 0.9 copies for other HPV types. HPV16 displayed the highest viral load, and it was the most prevalent. It was found that using contraceptive pills by female partners was associated with HPV infection. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  17. Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Swati P Ahir

    2013-01-01

    Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit

  18. Correlation between viral load of cytomegalovirus and tacrolimus and sirolimus levels in transplanted pediatric patients

    Directory of Open Access Journals (Sweden)

    Herlinda Reyes-Pérez

    2016-01-01

    Conclusions: These data support that the doses of immunosuppressive drugs do not correlate with the levels of the same in whole blood. Therefore, systemic levels of immunosuppressant should be constantly monitored together with CMV load. Meanwhile, a high correlation between viral load measured in whole blood and plasma was found.

  19. Probing the impact of loading rate on the mechanical properties of viral nanoparticles

    NARCIS (Netherlands)

    Snijder, J.; Ivanovska, I.L.; Baclayon, M.; Roos, W.H.; Wuite, G.J.L.

    2012-01-01

    The effects of changes in the loading rate during the forced dissociation of single bonds have been studied for a wide variety of interactions. Less is known on the loading rate dependent behaviour of more complex systems that consist of multiple bonds. Here we focus on viral nanoparticles, in

  20. The use of pooled viral load testing to identify antiretroviral treatment failure

    Science.gov (United States)

    Smith, Davey M.; May, Susanne J.; Pérez-Santiago, Josué; Strain, Matthew C.; Ignacio, Caroline C.; Haubrich, Richard H.; Richman, Douglas D.; Benson, Constance A.; Little, Susan J.

    2010-01-01

    Background To develop less costly methods to virologically monitor patients receiving antiretroviral therapy, we evaluated methods that use pooled blood samples and quantitative information available from viral load assays to monitor a cohort of patients on first-line antiretroviral therapy for virologic failure. Methods We evaluated 150 blood samples collected after 6 months of therapy from participants enrolled in a San Diego primary infection program between January 1998 and January 2007. Samples were screened for virologic failure with individual viral load testing, 10 × 10 matrix pools and minipools of five samples. For the pooled platforms (matrix and minipools), we used a search and retest algorithm based on the quantitative viral load data to resolve samples that remained ambiguous for virologic failure. Viral load thresholds were more than 500 and more than 1500 copies/ml for the matrix and more than 250 and more than 500 copies/ml for the minipool. Efficiency, accuracy and result turnaround times were evaluated. Results Twenty-three percent of cohort samples were detectable at more than 50 HIV RNA copies/ml. At an algorithm threshold of more than 500 HIV RNA copies/ml, both minipool and matrix methods used less than half the number of viral load assays to screen the cohort, compared with testing samples individually. Both pooling platforms had negative predictive values of 100% for viral loads of more than 500 HIV RNA copies/ml and at least 94% for viral loads of more than 250 HIV RNA copies/ml. Conclusion In this cohort, both pooling methods improved the efficiency of virologic monitoring over individual testing with a minimal decrease in accuracy. These methods may allow for the induction and sustainability of the virologic monitoring of patients receiving antiretroviral therapy in resource-limited settings. PMID:19730348

  1. Effects of interferon-α/β on HBV replication determined by viral load.

    Directory of Open Access Journals (Sweden)

    Yongjun Tian

    2011-07-01

    Full Text Available Interferons α and β (IFN-α/β are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low.

  2. Effects of Interferon-α/β on HBV Replication Determined by Viral Load

    Science.gov (United States)

    Tian, Yongjun; Chen, Wen-ling; Ou, Jing-hsiung James

    2011-01-01

    Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low. PMID:21829354

  3. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

    International Nuclear Information System (INIS)

    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs

  4. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs.

  5. Impact of collection method on assessment of semen HIV RNA viral load.

    Directory of Open Access Journals (Sweden)

    Brendan J W Osborne

    Full Text Available The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load.Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples.The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.

  6. Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

    DEFF Research Database (Denmark)

    Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik

    2018-01-01

    BACKGROUND: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. METHODS: Bronchoscopies...... fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n=126) was also studied. Optimal CMV PCR viral load cut off for CMV pneumonia diagnosis was determined using receiver operating characteristics...... (ROC). RESULTS: CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The AUC-ROC for CMV in BAL was 90% at the optimum cut off (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma...

  7. Congenital cytomegalovirus: association between dried blood spot viral load and hearing loss.

    Science.gov (United States)

    Walter, S; Atkinson, C; Sharland, M; Rice, P; Raglan, E; Emery, V C; Griffiths, P D

    2008-07-01

    To investigate the relation between cytomegalovirus (CMV) viral load on dried blood spots (DBS) from newborn biochemical screening ("Guthrie") cards, and sensorineural hearing loss (SNHL) in congenital CMV. Cross-sectional study with retrospective case-note review. Seven paediatric audiology departments in the United Kingdom. 84 children, median age 7 years: 43 with known congenital CMV, 41 with unexplained SNHL. Half a DBS was tested for CMV DNA viral load by quantitative real-time polymerase chain reaction (PCR). Pure tone average hearing thresholds (0.5-4 kHz). DBS CMV DNA viral load significantly correlated with hearing thresholds for the worse and better hearing ears (Spearman's rank correlations: r = 0.445, p = 0.008 and r = 0.481, p = 0.004 respectively). Multivariable logistic regression showed that the effect of DBS viral load on the risk of SNHL remained important, when age and central nervous system involvement had been taken into account (odds ratio (OR) 2.76, 95% confidence interval (CI) 1.14 to 6.63, p = 0.024). The mean log DBS viral load was significantly higher in children with SNHL than in those with normal hearing (2.69 versus 1.64, 95% CI -1.84 to -0.27, p = 0.01). 8/35 (23%) children with unexplained SNHL tested positive for CMV DNA on DBS. One false positive result was obtained. The risk of SNHL increased with DBS viral load. Further studies should investigate whether DBS CMV testing has a role in identifying asymptomatic congenitally infected neonates at risk of SNHL, and whether antiviral treatment can reduce this risk.

  8. Fully articulated four-point-bend loading fixture

    Science.gov (United States)

    Calomino, Anthony M. (Inventor)

    1991-01-01

    A fully articulated four-point bend loading fixture for Modulus of Rupture (MOR) and fracture toughness specimens utilizes an upper loading plate in combination with a lower loading plate. The lower plate has a pair of spring loaded ball bearings which seat in V-shaped grooves located in the upper plate. The ball bearings are carried in the arms of the lower plate. A load is applied to the specimen through steel rollers, one large roller and one smaller roller each located on both the upper and lower plates. The large rollers have needle roller bearings which enable a single loading roller to rotate relative to the plate to which it is attached.

  9. EVOLUTION OF HIV-1 VIRAL LOAD IN PATIENTS FOLLOWED-UP FOR OVER 3 YEARS

    Directory of Open Access Journals (Sweden)

    Labayru C

    2006-02-01

    Full Text Available ABSTRACTObjectives: To describe the evolution of a Human Immunodeficiency Virus Type 1 (HIV-1 infected patient cohort monitored for over 1,000 days.Methods: HIV-1 Viral Load (VL, CD4/l lymphocyte values and antiretroviral therapies given to the patients were evaluated throughout the follow-up period. We present a retrospective descriptive study of the HIV-1 VL determinations performed on 369 individuals followed-up for over 1,000 days.Results: The "non-detectable" VL ( 100.000 copies/ml from the interval of 0-75 days up to the interval of 501-1,000 days (t-test, p=0.005; at that point, results switched to the opposite.Conclusions: Both CD4/ cell count lower than 200x106 and patients receiving highly active antiretroviral therapies (HAART were related to "non-detectable" VL levels. In our series the time period between 700 and 1,000 days can be the maximum interval for benefits from therapy and virology evaluation.RESUMENObjetivo: Describir la evolución de una cohorte de pacientes con infección por el Virus de la Inmunodeficiencia Humana (VIH monitorizados durante más 3 años.Métodos: Durante el período de seguimiento se han evaluado en 396 individuos con infección VIH, seguidos durante más de 1000 días los parámetros de carga viral, valores de linfocitos CD4 y terapia antirretroviral.Resultados: Las porcentajes de carga viral no detectable (100.000 copias/ARN/ml, y su rango adquirió significación desde el intervalo de 0-75 días de seguimiento al de 501-100 días (t-test, p=0.005. Los recuentos de CD4 bajos (<200 en pacientes que recibieron Terapia antirretroviral de alta eficacia se asociaron a valores indetectables de carga viral.Conclusiones: En nuestra serie el período situado entre 700-100 días representó el intervalo de máximo beneficio para la evaluación virológica y terapéutica.

  10. Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus).

    Science.gov (United States)

    Stanton, Jeffrey J; Zong, Jian-Chao; Eng, Crystal; Howard, Lauren; Flanagan, Joe; Stevens, Martina; Schmitt, Dennis; Wiedner, Ellen; Graham, Danielle; Junge, Randall E; Weber, Martha A; Fischer, Martha; Mejia, Alicia; Tan, Jie; Latimer, Erin; Herron, Alan; Hayward, Gary S; Ling, Paul D

    2013-03-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elphas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions. In three elephants displaying clinical signs of illness, preclinical EEHV1 DNAemia was detectable, and peak whole-blood viral loads occurred 3-8 days after the onset of clinical signs. In two elephants with EEHV1 DNAemia that persisted for 7-21 days, no clinical signs of illness were observed. Detection of EEHV1 DNA in trunk washes peaked approximately 21 days after DNAemia, and viral genotypes detected during DNAemia matched those detected in subsequent trunk washes from the same elephant. In each of the five elephants, two distinct EEHV1 genotypes were identified in whole blood and trunk washes at different time points. In each case, these genotypes represented both an EEHV1A and an EEHV1B subtype. These data suggest that knowledge of viral loads could be useful for the management of elephants before or during clinical illness. Furthermore, sequential infection with both EEHV1 subtypes occurs in Asian elephants, suggesting that they do not elicit cross-protective sterilizing immunity. These data will be useful to individuals involved in the husbandry and clinical care of Asian elephants.

  11. KINETICS OF VIRAL LOADS AND GENOTYPIC ANALYSIS OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS-1 INFECTION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS)

    Science.gov (United States)

    Stanton, Jeffrey J.; Zong, Jian-Chao; Eng, Crystal; Howard, Lauren; Flanagan, Joe; Stevens, Martina; Schmitt, Dennis; Wiedner, Ellen; Graham, Danielle; Junge, Randall E.; Weber, Martha A.; Fischer, Martha; Mejia, Alicia; Tan, Jie; Latimer, Erin; Herron, Alan; Hayward, Gary S.; Ling, Paul D.

    2013-01-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elephas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions. In three elephants displaying clinical signs of illness, preclinical EEHV1 DNAemia was detectable, and peak whole-blood viral loads occurred 3–8 days after the onset of clinical signs. In two elephants with EEHV1 DNAemia that persisted for 7–21 days, no clinical signs of illness were observed. Detection of EEHV1 DNA in trunk washes peaked approximately 21 days after DNAemia, and viral genotypes detected during DNAemia matched those detected in subsequent trunk washes from the same elephant. In each of the five elephants, two distinct EEHV1 genotypes were identified in whole blood and trunk washes at different time points. In each case, these genotypes represented both an EEHV1A and an EEHV1B subtype. These data suggest that knowledge of viral loads could be useful for the management of elephants before or during clinical illness. Furthermore, sequential infection with both EEHV1 subtypes occurs in Asian elephants, suggesting that they do not elicit cross-protective sterilizing immunity. These data will be useful to individuals involved in the husbandry and clinical care of Asian elephants. PMID:23505702

  12. Residual viraemia in HIV-1-infected patients with plasma viral load

    DEFF Research Database (Denmark)

    Ostrowski, S.R.; Katzenstein, T.L.; Pedersen, Bente Klarlund

    2008-01-01

    )-microglobulin (+22 nmol/l, P = 0.016) and time-points with PCR-RV were also associated with higher IgA (+0.82 micromol/l, P = 0.035) and CD8-count (+1.18-fold, P = 0.001). Patients with TMA-RV in the study-period had higher HIV-1 RNA pre-HAART (P = 0.032). RV was not associated with proviral-HIV-1-DNA, CD4......Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2...

  13. Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

    Science.gov (United States)

    2013-01-01

    SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation. PMID:24092851

  14. Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 ...

    African Journals Online (AJOL)

    Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected untreated children in Kenya; implication for immunodeficiency and AIDS progression. Washingtone Ochieng, Dorington Ogoyi, Francis J Mulaa, Simon Ogola, Rachel Musoke, Moses G Otsyula ...

  15. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    The overlapping epidemiology of human immunodeficiency virus (HIV) infection and tuberculosis (TB) is expected in Nigeria that is ranked 10th amongst the 22 countries that bears the burden of TB worldwide. This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) in a CD4 cell count ...

  16. Suppression of HIV-1 viral load after multiple changes in high active ...

    African Journals Online (AJOL)

    1-infected patients. However, the virus persists ... chronological changes in HIV viral load and CD4+ T-cell count, and treatment outcomes of multiple combinations of .... Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the ...

  17. Epstein-Barr viral load assessment in immunocompetent patients with fulminant infectious mononucleosis.

    NARCIS (Netherlands)

    Laar, J.A. van; Buysse, C.M.; Vossen, A.C.; Hjalmarsson, B.; Berg, B. van de; Lom, K. van; Deinum, J.

    2002-01-01

    We describe 2 immunocompetent adolescents with fulminant infectious mononucleosis and virus-associated hemophagocytosis. A new quantitative polymerase chain reaction revealed high serum Epstein-Barr virus DNA levels in these patients. One patient died with an increasing viral load not responding to

  18. The number of herpes simplex virus-infected neurons and the number of viral genome copies per neuron correlate with the latent viral load in ganglia.

    Science.gov (United States)

    Hoshino, Yo; Qin, Jing; Follmann, Dean; Cohen, Jeffrey I; Straus, Stephen E

    2008-03-01

    The latent viral load is the most important factor that predicts reactivation rates of animals latently infected with herpes simplex virus (HSV). To estimate the latent viral load, individual latently infected mouse trigeminal ganglia were dispersed into single cell suspensions and plated into 96-well real-time PCR plates, and HSV-2 genome copies were measured. By assuming a Poisson distribution for both the number of HSV-2 infected cells per well and the number of HSV-2 genome copies per infected cell, the numbers of infected cells and mean genome copies per infected cell were determined. Both the number of HSV-2 infected cells and the mean HSV-2 genome copy per infected cell significantly correlated with the latent viral load (p<10(-4)), indicating that both factors are responsible for the increase in the latent viral load.

  19. Quantitative molecular viral loads in 7 horses with naturally occurring equine herpesvirus-1 infection.

    Science.gov (United States)

    Estell, K E; Dawson, D R; Magdesian, K G; Swain, E; Laing, S T; Siso, S; Mapes, S; Pusterla, N

    2015-11-01

    Data associating quantitative viral load with severity, clinical signs and survival in equine herpesvirus-1 myeloencephalopathy (EHM) have not been reported. To report the clinical signs, treatment, and temporal progression of viral loads in 7 horses with naturally occurring EHM and to examine the association of these factors with survival. Retrospective case series. The population included 7 horses with EHM presented to the University of California, Davis William R. Pritchard Veterinary Medical Teaching Hospital from May to September 2011. Horses were graded using a neurological grading scale. Daily quantitative PCR was performed on nasal secretions and whole blood. Treatment, survival, outcome and histopathology were reported. At presentation, one horse was neurological grade 5/5, 3 were grade 4/5 and 3 were grade 3/5. All were treated with anti-inflammatory drugs, valacyclovir and management in a sling if necessary. All were infected with equine herpesvirus-1 of DNA polymerase D752 genotype. Peak viral load in nasal secretions and blood of 5 survivors ranged from 6.9 × 10(3) to 2.81 × 10(5) (median 5.11 × 10(4) ) and from 143 to 4340 gB gene copies/million eukaryotic cells (median 3146), respectively. The 2 nonsurvivors presented with grade 3/5 neurological signs and progressed to encephalopathy. Peak viral load was higher in nonsurvivors, with levels in nasal secretions of 1.9 × 10(9) and 2.2 × 10(9) and in blood of 2.05 × 10(4) and 1.02 × 10(5) gB gene copies/million eukaryotic cells. Case fatality was 2/7. Nonsurvivors had viral loads 1000-fold higher in nasal secretions and 10-fold higher in blood than survivors. There was no relationship between severity of clinical signs at presentation and survival. Thus, encephalopathy and high viral load were negatively associated with survival in this population. Further research should be performed to determine whether high viral loads are associated with encephalopathy and poor prognosis. The Summary is

  20. Engineering to Control Noise, Loading, and Optimal Operating Points

    International Nuclear Information System (INIS)

    Mitchell R. Swartz

    2000-01-01

    Successful engineering of low-energy nuclear systems requires control of noise, loading, and optimum operating point (OOP) manifolds. The latter result from the biphasic system response of low-energy nuclear reaction (LENR)/cold fusion systems, and their ash production rate, to input electrical power. Knowledge of the optimal operating point manifold can improve the reproducibility and efficacy of these systems in several ways. Improved control of noise, loading, and peak production rates is available through the study, and use, of OOP manifolds. Engineering of systems toward the OOP-manifold drive-point peak may, with inclusion of geometric factors, permit more accurate uniform determinations of the calibrated activity of these materials/systems

  1. Cognitive load predicts point-of-care ultrasound simulator performance.

    Science.gov (United States)

    Aldekhyl, Sara; Cavalcanti, Rodrigo B; Naismith, Laura M

    2018-02-01

    The ability to maintain good performance with low cognitive load is an important marker of expertise. Incorporating cognitive load measurements in the context of simulation training may help to inform judgements of competence. This exploratory study investigated relationships between demographic markers of expertise, cognitive load measures, and simulator performance in the context of point-of-care ultrasonography. Twenty-nine medical trainees and clinicians at the University of Toronto with a range of clinical ultrasound experience were recruited. Participants answered a demographic questionnaire then used an ultrasound simulator to perform targeted scanning tasks based on clinical vignettes. Participants were scored on their ability to both acquire and interpret ultrasound images. Cognitive load measures included participant self-report, eye-based physiological indices, and behavioural measures. Data were analyzed using a multilevel linear modelling approach, wherein observations were clustered by participants. Experienced participants outperformed novice participants on ultrasound image acquisition. Ultrasound image interpretation was comparable between the two groups. Ultrasound image acquisition performance was predicted by level of training, prior ultrasound training, and cognitive load. There was significant convergence between cognitive load measurement techniques. A marginal model of ultrasound image acquisition performance including prior ultrasound training and cognitive load as fixed effects provided the best overall fit for the observed data. In this proof-of-principle study, the combination of demographic and cognitive load measures provided more sensitive metrics to predict ultrasound simulator performance. Performance assessments which include cognitive load can help differentiate between levels of expertise in simulation environments, and may serve as better predictors of skill transfer to clinical practice.

  2. [Clinical study of low cytomegalovirus viral load thresholds for preemptive antiviral therapy in hematopoietic cell transplant recipients].

    Science.gov (United States)

    Li, L; Wang, Y; Yan, C H; Huang, X J

    2018-03-01

    Objective: To investigate the threshold of cytomegalovirus (CMV) DNAemia for preemptive antiviral therapy in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Viral load between 1×10(3) copies/ml and 5×10(3) copies/ml was defined as low viral load by real time Q-PCR. Clinical data and outcome were collected. Results: A total of 95 allo-HSCT recipients with low viral load from September 2014 to February 2015 were recruited in this study. The control group included 37 patients who received preemptive initial antiviral therapy. The other 58 patients didn't received antiviral treatment after positive viremia was confirmed. During monitoring, CMV viremia was cleared spontaneously in 17 patients of study group. Among 41 patients with continuous positive viremia in study group, 26 patients received antiviral therapy after second positivity including 18 with viral load >5×10(3) copies/ml, 2 with fever but still low viral load, 2 with hemorrhagic cystitis and low viral load, 4 with continuous low viral load. Eleven patients received antiviral therapy after the third positivity including 5 with viral load >5×10(3) copies/ml, 1 low viral load patient with fever and diarrhea, 5 with continuous low viral load. Only 4 patients received antiviral therapy after the fourth positivity of >5×10(3) copies/ml. In the study group, 35 cases received ganciclovir and 6 cases received foscarnet. The incidence of neutropenia did not differ significantly between study and control groups [minimum of neutrophil count: (1.63±0.41)×10(9)/L vs. (1.58±0.36)×10(9)/L]. The proportion of viral load greater than 5×10(3) copies/ml in the first week was comparable in two groups. Successful viral clearance rate was not statistically different ( P =0.87). Of all 95 patients, no CMV diseases developed, neither did patient die of CMV infection. Conclusions: Spontaneous clearance of viremia occurs in some patients receiving allo-HSCT with low CMV viral load

  3. Rapid reduction in HIV viral load in late pregnancy with raltegravir: a case report.

    Science.gov (United States)

    Cha, Agnes; Shaikh, Raisa; Williams, Shalonda; Berkowitz, Leonard L

    2013-01-01

    The use of raltegravir (RAL) is not preferred to prevent perinatal transmission in pregnancy due to lack of safety and pharmacokinetic data in this population. Data have been limited to few case reports of patients who present for treatment late in pregnancy, have multidrug resistance, or have poor adherence, requiring an additional class such as an integrase inhibitor to further lower viral load. This case report describes and supports the initiation of RAL in very late pregnancy (week 33) to rapidly decrease viral load and successfully prevent perinatal transmission. By increasing the efficacy and safety data of RAL use in pregnancy, we believe this report can help provide some guidance on the management of complex cases.

  4. Brachial amyotrophic diplegia in the setting of complete HIV viral load suppression.

    Science.gov (United States)

    Cachia, David; Izzy, Saef; Ionete, Carolina; Salameh, Johnny

    2012-12-06

    Brachial amyotrophic diplegia (BAD) is a rare segmental form of motor neuron disease which presents with asymmetric lower motor neuron weakness largely confined to the upper extremities (UE). In the case being reported, a 62-year-old gentleman on antiretroviral treatment since 1993, presented with left-arm weakness in 2007 that quickly progressed to involve the right arm. Complete HIV-viral load suppression had been achieved since 2003. Examination revealed lower motor neuron weakness in both UEs, worse proximally than distally and normal strength in the lower extremities (LEs). Nerve conduction studies showed reduced amplitudes of bilateral median and ulnar nerves' motor responses. Needle electromyography of bilateral UE showed active and chronic denervation/reinnervation changes with normal findings in both LEs. MRI of the cervical spine showed cord atrophy. This is the first case report describing a patient who presented with BAD in the setting of complete HIV-viral load suppression for many years.

  5. Comparison of the Abbott Realtime HIV-1 and HCV viral load assays with commercial competitor assays.

    Science.gov (United States)

    Schutten, Martin

    2008-07-01

    The introduction of commercially available quantitative HIV-1 RNA detection methods at the end of the last century has had a significant impact on the management of patients requiring treatment. Similarly for hepatitis C virus (HCV), clinical decision-making with respect to initiation and prolonging therapy is largely based on data from viral load assays. The methods developed in the early 1990s and further improved since then still have significant drawbacks. For example, they are labor intensive, have a small dynamic range and are contamination sensitive. The development of real-time detection techniques for reverse transcription PCR has in part solved these problems. In the present review the advantages and disadvantages of the recently marketed Abbott Realtime HCV and HIV-1 viral load assays relative to their competitors will be discussed.

  6. Gastrointestinal viral load and enteroendocrine cell number are associated with altered survival in HIV-1 infected individuals.

    Directory of Open Access Journals (Sweden)

    Guido van Marle

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS. The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM enrolled pre-HAART (Highly Active Antiretroviral Therapy. We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum and somatostatin (duodenum and colon immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

  7. Comparison of asymptomatic and symptomatic rhinovirus infections in university students: incidence, species diversity, and viral load.

    Science.gov (United States)

    Granados, Andrea; Goodall, Emma C; Luinstra, Kathy; Smieja, Marek; Mahony, James

    2015-08-01

    Human rhinovirus (HRV) infections are common but poorly characterized in university students. Thus, we characterized asymptomatic and symptomatic HRV infections by incidence, species diversity, and viral load of 502 university students during September and October of 2010 and 2011 from nasal swabs and electronically submitted symptom questionnaires. We tested all symptomatic students and randomly sampled participants who remained asymptomatic (n=25/week, over 8 weeks each study year) on a weekly basis by real-time PCR and sequenced HRV positives. HRV was identified in 33/400 (8.3%) and 85/92 (92.4%) of the asymptomatic and symptomatic students, respectively. We identified a higher than previously reported rate of HRV-B in both groups, although the distribution of HRV species was similar (P=0.37). Asymptomatic viral load averaged 1.2 log10 copies/mL lower than symptomatic HRV (P<0.001). In conclusion, asymptomatic HRV activity preceded peak symptomatic activity in September and October and was associated with lower viral load. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Behavioral and Other Characteristics Associated with HIV Viral Load in an Outpatient Clinic.

    Directory of Open Access Journals (Sweden)

    Paul L Sacamano

    Full Text Available Persons living with HIV (PLWH who are engaged in care, yet not virally suppressed, represent a risk for transmission and opportunity for risk reduction interventions. This study describes characteristics of an outpatient clinic cohort of PLWH by laboratory confirmed viral suppression status and examines associations with demographics and sexual and drug use behaviors gathered through questionnaire. From a sample of 500 clinic patients, 438 were prescribed antiretroviral treatment (ART and 62 were not. Among the 438 on ART, 72 (16.4% were not virally suppressed at the most recent lab draw. Compared to individuals with a suppressed viral load, those that were unsuppressed were more likely to: be black (79.2% vs. 64.2%; p = 0.014; earn below $25,000/year (88.9% vs. 65.0%; p < 0.001; be of a younger age (47.8 vs. 50.0 mean years; p = 0.009; be on opiate substitution (14.1% vs. 6.3%; p = 0.023; and acknowledge poly-substance (38.9% vs. 24.4%; p = 0.012 and excessive alcohol use (13.9% vs. 6.0%; p = 0.019. Conversely, a smaller proportion of those with an unsuppressed viral load had multiple sex partners in the previous 30 days (39.8% vs. 58.5%; p = 0.003. In multivariable regression of those on ART, the prevalence of an unsuppressed viral load was 3% lower with each increasing year of age (aPR: 0.97; 95% CI: 0.95, 0.99 and 47% lower with income over $25,000/year (aPR: 0.33; 95% CI: 0.16, 0.70. In a separate analysis of all 500 subjects, ART was less frequently prescribed to blacks compared to whites, heterosexuals, those with lower education and income, and persons with active substance use. Findings confirm that a large proportion of PLWH and engaged in care were not virally suppressed and continued behaviors that risk transmission, indicating the need for screening, prevention counseling and access to ancillary services to lower the incidence of HIV infections.

  9. Monitoring HIV viral load in resource limited settings: still a matter of debate?

    Directory of Open Access Journals (Sweden)

    Mireia Arnedo

    Full Text Available INTRODUCTION: Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS is still a matter of debate. DESIGN: To assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya. METHODS: Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method. RESULTS: 926 patients were included. Among 274 (29.6% patients with detectable viral load, 55 (5.9% experienced treatment failure (viral load >5.000 copies/ml; 61.8% were female and 10 (18.2% had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189. Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000. Eighteen out of 55 (33% samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs in 15 out of 18 samples (83%. Among patients carrying RAMs, 12/15 (81% harboured RAMs associated to thymidine analogues (TAMs. All of them (100% showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS. CONCLUSIONS: Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen.

  10. HIV viral load monitoring among key populations in low- and middle-income countries: challenges and opportunities.

    Science.gov (United States)

    Schwartz, Sheree R; Kavanagh, Matthew M; Sugarman, Jeremy; Solomon, Sunil S; Njindam, Illiassou M; Rebe, Kevin; Quinn, Thomas C; Toure-Kane, Coumba; Beyrer, Chris; Baral, Stefan

    2017-11-01

    Key populations bear a disproportionate HIV burden and have substantial unmet treatment needs. Routine viral load monitoring represents the gold standard for assessing treatment response at the individual and programme levels; at the population-level, community viral load is a metric of HIV programme effectiveness and can identify "hotspots" of HIV transmission. Nevertheless, there are specific implementation and ethical challenges to effectively operationalize and meaningfully interpret viral load data at the community level among these often marginalized populations. Viral load monitoring enhances HIV treatment, and programme evaluation, and offers a better understanding of HIV surveillance and epidemic trends. Programmatically, viral load monitoring can provide data related to HIV service delivery coverage and quality, as well as inequities in treatment access and uptake. From a population perspective, community viral load data provides information on HIV transmission risk. Furthermore, viral load data can be used as an advocacy tool to demonstrate differences in service delivery and to promote allocation of resources to disproportionately affected key populations and communities with suboptimal health outcomes. However, in order to perform viral load monitoring for individual and programme benefit, health surveillance and advocacy purposes, careful consideration must be given to how such key population programmes are designed and implemented. For example, HIV risk factors, such as particular sex practices, sex work and drug use, are stigmatized or even criminalized in many contexts. Consequently, efforts must be taken so that routine viral load monitoring among marginalized populations does not cause inadvertent harm. Furthermore, given the challenges of reaching representative samples of key populations, significant attention to meaningful recruitment, decentralization of care and interpretation of results is needed. Finally, improving the interoperability of

  11. An International Collaboration To Standardize HIV-2 Viral Load Assays: Results from the 2009 ACHIEV2E Quality Control Study▿

    OpenAIRE

    Damond, F.; Benard, A.; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente

    2011-01-01

    Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHIEV2E study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own H...

  12. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: a nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik Bygum; Andersen, Stig; Madsen, Poul Henning

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  13. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik; Andersen, Stig; Madsen, Poul Henning

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  14. The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States.

    Science.gov (United States)

    Cates, Jordan E; Westreich, Daniel; Edmonds, Andrew; Wright, Rodney L; Minkoff, Howard; Colie, Christine; Greenblatt, Ruth M; Cejtin, Helen E; Karim, Roksana; Haddad, Lisa B; Kempf, Mirjam-Colette; Golub, Elizabeth T; Adimora, Adaora A

    2015-01-01

    To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

  15. Influence of maintained hemodialysis on viral load in patients with end-stage renal disease with HBV infection

    Directory of Open Access Journals (Sweden)

    ZHANG Huifang

    2017-07-01

    Full Text Available In the patients with end-stage renal disease (ESRD with hepatitis B virus (HBV infection who underwent hemodialysis, the viral load of HBV DNA is relatively low and stable. For this phenomenon, some studies suggest that hemodialysis can reduce the HBV DNA load. The mechanism, which remains unclear, may be as follows: when HBV DNA enters the dialysate through the dialysis membrane, it was adsorbed onto the dialysis membrane; some virus particles were destroyed, and antiviral substances were produced in the course of hemodialysis. At present, there is no consensus on the mechanism responsible for the influence of maintained hemodialysis on the viral load of HBV DNA. This article reviews the factors involved in the influence of maintained hemodialysis on the viral load in ESRD patients with HBV infection and the recent progress.

  16. In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian patients.

    Science.gov (United States)

    de Lima-Stein, Mariana Leão; Alkmim, Wagner Tadeu; Bizinoto, Maria Clara de Souza; Lopez, Luis Fernandez; Burattini, Marcelo Nascimento; Maricato, Juliana Terzi; Giron, Leila; Sucupira, Maria Cecília Araripe; Diaz, Ricardo Sobhie; Janini, Luiz Mario

    2014-09-01

    Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- >A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.

  17. GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

    Science.gov (United States)

    Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

    2017-07-21

    Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

  18. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    -68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...... vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond...

  19. Meticulous plasma isolation is essential to avoid false low-level viraemia in Roche Cobas HIV-1 viral load assays.

    Science.gov (United States)

    Mortier, Virginie; Vancoillie, Leen; Dauwe, Kenny; Staelens, Delfien; Demecheleer, Els; Schauvliege, Marlies; Dinakis, Sylvie; Van Maerken, Tom; Dessilly, Géraldine; Ruelle, Jean; Verhofstede, Chris

    2017-10-24

    Pre-analytical sample processing is often overlooked as a potential cause of inaccurate assay results. Here we demonstrate how plasma, extracted from standard EDTA-containing blood collection tubes, may contain traces of blood cells consequently resulting in a false low-level HIV-1 viral load when using Roche Cobas HIV-1 assays. The presence of human DNA in Roche Cobas 4800 RNA extracts and in RNA extracts from the Abbott HIV-1 RealTime assay was assessed by quantifying the human albumin gene by means of quantitative PCR. RNA was extracted from plasma samples before and after an additional centrifugation and tested for viral load and DNA contamination. The relation between total DNA content and viral load was defined. Elevated concentrations of genomic DNA were detected in 28 out of 100 Cobas 4800 extracts and were significantly more frequent in samples processed outside of the AIDS Reference Laboratory. An association between genomic DNA presence and spurious low-level viraemia results was demonstrated. Supplementary centrifugation of plasma before RNA extraction eliminated the contamination and the false viraemia. Plasma isolated from standard EDTA-containing blood collection tubes may contain traces of HIV DNA leading to false viral load results above the clinical cutoff. Supplementary centrifugation of plasma before viral load analysis may eliminate the occurrence of this spurious low-level viraemia.

  20. The semen microbiome and its relationship with local immunology and viral load in HIV infection.

    Directory of Open Access Journals (Sweden)

    Cindy M Liu

    2014-07-01

    Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2  = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

  1. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....

  2. CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone.

    Science.gov (United States)

    Hoffmann, Christopher J; Maritz, Jean; van Zyl, Gert U

    2016-02-01

    CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance. Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen. © 2015 John Wiley & Sons Ltd.

  3. Chicken parvovirus viral loads in cloacal swabs from malabsorption syndrome-affected and healthy broilers.

    Science.gov (United States)

    Finkler, Fabrine; de Lima, Diane Alves; Cerva, Cristine; Cibulski, Samuel Paulo; Teixeira, Thais Fumaco; Dos Santos, Helton Fernandes; de Almeida, Laura Lopes; Roehe, Paulo Michel; Franco, Ana Cláudia

    2016-12-01

    Chicken parvovirus (ChPV) has been associated with malabsorption syndrome (MAS) in broilers. However, the participation of this virus in such syndrome is unclear, since it may be detected in diseased and healthy chickens. In the course of these studies, it was argued whether ChPV genome loads might be correlated to the occurrence of MAS. To check such a hypothesis, a SYBR green-based quantitative polymerase chain reaction was developed to detect and quantify ChPV genomes. Cloacal swabs from 68 broilers with MAS and 59 from healthy animals were collected from different poultry farms. Genomes of ChPV were detected in all samples, regardless of their health status. However, viral genome loads in MAS-affected broilers were significantly higher (1 × 10 5 genome copies per 100 ng DNA) than in healthy animals (1.3 × 10 3 GC/100 ng DNA). These findings indicate that there is an association between high ChPV genome loads and the occurrence of MAS in broilers.

  4. Someone to count on: social support as an effect modifier of viral load suppression in a prospective cohort study.

    Science.gov (United States)

    Friedman, M Reuel; Coulter, Robert W S; Silvestre, Anthony J; Stall, Ron; Teplin, Linda; Shoptaw, Steve; Surkan, Pamela J; Plankey, Michael W

    2017-04-01

    Though functional social support has been shown to serve as a protective factor for HIV viral load suppression in other populations, scant research has examined this relationship among men who have sex with men (MSM) in the United States. We assessed characteristics of social support, effects of social support on HIV viral load, and moderation by social support of the relationship between psychosocial indicators of a synergistic epidemic (syndemic) and HIV viral load. We analyzed longitudinal data from HIV-positive MSM using antiretroviral therapy who were enrolled in the Multicenter AIDS Cohort Study between 2002 and 2009 (n = 712). First, we conducted reliability assessments of a one-item social support measure. Then, we conducted a series of generalized longitudinal mixed models to assess our research questions. Moderation was assessed using an interaction term. A three-level (low/medium/high) social support variable demonstrated high reliability (intraclass correlation coefficients  = 0.72; 95% CI: 0.70, 0.75). Black and Hispanic MSM reported lower social support than their White counterparts (p social support (p social support (p social support levels were associated with greater viral load suppression and lower viral load means (p Social support moderated the relationships between syndemic and HIV viral load (p HIV-positive MSM, particularly those of color, may benefit greatly from interventions that can successfully boost functional social support. Creating strengths-based interventions may also have particularly high impact among HIV-positive MSM with the highest psychosocial burdens.

  5. Impact of two different commercial DNA extraction methods on BK virus viral load

    Directory of Open Access Journals (Sweden)

    Massimiliano Bergallo

    2016-03-01

    Full Text Available Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France and manual QIAGEN extraction (QIAGEN Hilden, Germany. BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit, for the extraction of BK virus from serum and urine specimens.

  6. Expansion of Viral Load Testing and the Potential Impact on HIV Drug Resistance.

    Science.gov (United States)

    Raizes, Elliot; Hader, Shannon; Birx, Deborah

    2017-12-01

    The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Sustained viral load and late death in Rag2-/- mice after influenza A virus infection

    Directory of Open Access Journals (Sweden)

    Schughart Klaus

    2010-07-01

    Full Text Available Abstract The importance of the adaptive immune response for secondary influenza infections and protection from a lethal challenge after vaccination has been well documented. However, some controversy still exists concerning the specific involvement of B and T cells during a primary infection. Here, we have followed the survival, weight loss, viral load and lung pathology in Rag2-/- knock-out mice after infection with influenza A virus (H1N1. Infected wild type mice initially lost weight early after infection but then cleared the virus and recovered. Rag2-/- mice, however, showed similar weight loss kinetics in the early stages after infection but weight loss continued post infection and culminated in death. In contrast to wild type mice, Rag2-/- mice were not able to clear the virus, despite an increased inflammatory response. Furthermore, they did not recruit virus-specific lymphocytes into the lung in the later stages after infection and exhibited sustained pulmonary lesions.

  8. Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men

    Science.gov (United States)

    McGinnis, Kathleen A.; Fiellin, David A.; Tate, Janet P.; Cook, Robert L; Braithwaite, R. Scott; Bryant, Kendall J.; Edelman, E. Jennifer; Gordon, Adam J.; Kraemer, Kevin L.; Maisto, Stephen; Justice, Amy C.

    2015-01-01

    The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation. Our goal was to compare number of drinks to “feel a buzz or high” among HIV infected and uninfected men, stratified by viral load (VL) suppression. Data includes 1,478 HIV infected and 1,170 uninfected men in the Veterans Aging Cohort Study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = −0.14 for VL500; pdrinks to feel a buzz. Future research on the relationship between alcohol and HIV should consider the role of VL suppression. PMID:26936030

  9. Which adherence measure - self-report, clinician recorded or pharmacy refill - is best able to predict detectable viral load in a public ART programme without routine plasma viral load monitoring?

    Science.gov (United States)

    Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2016-07-01

    Combination antiretroviral therapy (cART) suppresses viral replication to an undetectable level if a sufficiently high level of adherence is achieved. We investigated which adherence measurement best distinguishes between patients with and without detectable viral load in a public ART programme without routine plasma viral load monitoring. We randomly selected 870 patients who started cART between May 2009 and April 2012 in 10 healthcare facilities in Addis Ababa, Ethiopia. Six hundred and sixty-four (76.3%) patients who were retained in HIV care and were receiving cART for at least 6 months were included and 642 had their plasma HIV-1 RNA concentration measured. Patients' adherence to cART was assessed according to self-report, clinician recorded and pharmacy refill measures. Multivariate logistic regression model was fitted to identify the predictors of detectable viremia. Model accuracy was evaluated by computing the area under the receiver operating characteristic (ROC) curve. A total of 9.2% and 5.5% of the 642 patients had a detectable viral load of ≥40 and ≥400 RNA copies/ml, respectively. In the multivariate analyses, younger age, lower CD4 cell count at cART initiation, being illiterate and widowed, and each of the adherence measures were significantly and independently predictive of having ≥400 RNA copies/ml. The ROC curve showed that these variables altogether had a likelihood of more than 80% to distinguish patients with a plasma viral load of ≥400 RNA copies/ml from those without. Adherence to cART was remarkably high. Self-report, clinician recorded and pharmacy refill non-adherence were all significantly predictive of detectable viremia. The choice for one of these methods to detect non-adherence and predict a detectable viral load can therefore be based on what is most practical in a particular setting. © 2016 John Wiley & Sons Ltd.

  10. A sensitive branched DNA HIV-1 signal amplification viral load assay with single day turnaround.

    Directory of Open Access Journals (Sweden)

    Mark A Baumeister

    Full Text Available Branched DNA (bDNA is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA ("Versant Assay" currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16-18 h to 2.5 h, composition of only the "Lysis Diluent" solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135 showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements.

  11. Disseminated HIV-Associated Kaposi’s Sarcoma With High CD4 Cell Count And Low Viral Load

    Directory of Open Access Journals (Sweden)

    Diana Pereira Anjos

    2017-12-01

    Full Text Available Kaposi’s sarcoma is considered an acquired immunodeficiency syndrome-defining illness and is caused by human herpesvirus 8. It has been associated with patients infected with human immunodeficiency virus (HIV who have CD4 T lymphocytes <200 cells/uL and high viral loads. We report a case of a 23-year old woman infected with HIV-1 and receiving antiretroviral treatment since diagnosis, with high CD4 cell count and low viral load that presented with disseminated Kaposi’s sarcoma. Clinicians should be aware of the occurrence of Kaposi’s sarcoma despite robust CD4 cell counts.

  12. Role of coxsackievirus and adenovirus receptor (CAR) expression and viral load of adenovirus and enterovirus in patients with dilated cardiomyopathy.

    Science.gov (United States)

    Sharma, Mirnalini; Mishra, Baijayantimala; Saikia, Uma Nahar; Bahl, Ajay; Ratho, Radha Kanta; Talwar, Kewal Kishan

    2016-01-01

    Enteroviruses (EVs) and adenoviruses (AdVs) are two important etiological agents of viral myocarditis and dilated cardiomyopathy (DCM). Both these viruses share a common receptor, the coxsackievirus and adenovirus receptor (CAR), for their infection. However, the role of viral load and CAR expression in disease severity has not yet been completely elucidated. The present study aimed to determine viral load of EV and AdV in DCM patients and correlate them with the level of CAR expression in these patients. Sixty-three DCM cases and 30 controls, each of whom died of heart disease other than DCM and non-cardiac disease respectively, were included. Viral load was determined by TaqMan real-time PCR using primers and probes specific for the AdV hexon gene and the 5'UTR region of EV. The CAR mRNA level was semi-quantitated by RT-PCR, and antigen expression was studied by immunohistochemistry. A significantly high AdV load (p < 0.05) and CAR expression (p < 0.05) were observed in DCM cases versus controls, whereas the EV load showed no significant difference. The data suggests a clinical threshold of 128 AdV copies/500 ng of DNA for DCM, with 66.7 % sensitivity and 65 % specificity. A positive correlation between AdV load and CAR expression (p < 0.001) was also observed in DCM cases. The high adenoviral load and increased CAR expression in DCM and their association with adverse disease outcome indicates role of both virus and receptor in disease pathogenesis. Thus, the need for targeting both the virus and the receptor for treatment of viral myocarditis and early DCM requires further confirmation with larger studies.

  13. CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system.

    Science.gov (United States)

    Durrant, Douglas M; Daniels, Brian P; Pasieka, TracyJo; Dorsey, Denise; Klein, Robyn S

    2015-12-15

    Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni's post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means ± SEM. Differences were considered significant if P ≤ 0.05. As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5(-/-) mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5(-/-) mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5(-/-) mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5(-/-) mice, however, were associated with decreased numbers of infiltrating mononuclear cells

  14. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  15. Association between feline immunodeficiency virus (FIV) plasma viral RNA load, concentration of acute phase proteins and disease severity.

    Science.gov (United States)

    Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne

    2014-08-01

    Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Point Coordination Function WLAN Traffic Loadings | Ani | Nigerian ...

    African Journals Online (AJOL)

    WLAN's ability to provide high capacity links, mobility and low acquisition cost played considerable positive role in its popularity. The operation of WLAN in ... traffic loadings is presented. Influence of traffic loadings on WLAN quality of service (QoS) parameters was analyzed using computer simulation modeling technique.

  17. Higher HIV RNA Viral Load in Recent Patients with Symptomatic Acute HIV Infection in Lyon University Hospitals.

    Directory of Open Access Journals (Sweden)

    Isabelle Girerd-Genessay

    Full Text Available Increased human immunodeficiency virus (HIV virulence at infection has been suggested by a meta-analysis based on viral load and CD4 T lymphocytes (CD4 count during acute infection. This result was obtained after secondary analyses of large databases, facilitating the detection of differences. Similar finding in cohorts of more modest sample size would indicate that the effect could be more substantial.Change from initial CD4 count and HIV viral load after acute HIV infection by calendar year was explored in patients treated at Lyon University hospitals. All patients admitted to our hospitals with acute HIV infection between 1996 and 2013 were included in our study. Initial CD4 count and viral load before the start of anti-retroviral treatment were analyzed. Trends over time were assessed in linear models.Initial CD4 count remained similar over time. However, in 2006-2013, initial viral load rose significantly (+1.12 log10/ml/year, p = 0.01.Our data, obtained from a single hospital cohort, confirmed findings from a large meta-analysis, showed increased initial viremia at acute HIV infection since 2006 and suggesting potentially higher HIV virulence in recent years.

  18. The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

    Science.gov (United States)

    Davies, Mary-Ann; Boulle, Andrew; Technau, Karl; Eley, Brian; Moultrie, Harry; Rabie, Helena; Garone, Daniela; Giddy, Janet; Wood, Robin; Egger, Matthias; Keiser, Olivia

    2012-11-01

    To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Analysis of data from children (CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children. © 2012 Blackwell Publishing Ltd.

  19. Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive MSM and association with persistence

    NARCIS (Netherlands)

    Marra, Elske; King, Audrey; van Logchem, Elske; van der Weele, Pascal; Mooij, Sofie H.; Heijman, Titia; Meijer, Chris J. L. M.; Verhagen, Dominique W. M.; van der Sande, Marianne A. B.; Schim van der Loeff, Maarten F.

    2018-01-01

    Does anal HPV viral load explain the difference in anal HPV persistence between HIV-negative and -positive men who have sex with men (MSM)? MSM 18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped

  20. Influence of the membrane structure plan shape on the displacements under point load

    Directory of Open Access Journals (Sweden)

    Milošević Vuk S.

    2016-01-01

    Full Text Available Deformations of membrane structures under external loads are much more prominent compared to other structures and structural materials. External area loads cause large displacements and redistribution of internal tension forces. Point loads have a less significant impact on changes of internal forces, but a more significant role in creation of local deformations. Previous researches have shown the influence of position and intensity of point loads on the deformations of membrane structures. The aim of this research is to investigate the influence of plan shape of the membrane structure on the displacements under point load. The influence of rhombic shaped plans with different diagonal lengths and ratios is explored. The research is conducted on numerical models in the specialized software Sofistik. Models are loaded with point loads in the point where diagonals intersect and the results are compared.

  1. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

    Directory of Open Access Journals (Sweden)

    Ricard Dominique

    2010-05-01

    Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

  2. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen

    Science.gov (United States)

    Mealey, Robert H.; Leib, Steven R.; Littke, Matt H.; Wagner, Bettina; Horohov, David W.; McGuire, Travis C.

    2009-01-01

    Effective DNA-based vaccines against lentiviruses will likely induce CTL against conserved viral proteins. Equine infectious anemia virus (EIAV) infects horses worldwide, and serves as a useful model for lentiviral immune control. Although attenuated live EIAV vaccines have induced protective immune responses, DNA-based vaccines have not. In particular, DNA-based vaccines have had limited success in inducing CTL responses against intracellular pathogens in the horse. We hypothesized that priming with a codon-optimized plasmid encoding EIAV Gag p15/p26 with co-administration of a plasmid encoding an equine IL-2/IgG fusion protein as a molecular adjuvant, followed by boosting with a vaccinia vector expressing Gag p15/p26, would induce protective Gag-specific CTL responses. Although the regimen induced Gag-specific CTL in four of seven vaccinated horses, CTL were not detected until after the vaccinia boost, and protective effects were not observed in EIAV challenged vaccinates. Unexpectedly, vaccinates had significantly higher viral loads and more severe clinical disease, associated with the presence of vaccine-induced CTL. It was concluded that 1.) further optimization of the timing and route of DNA immunization was needed for efficient CTL priming in vivo, 2.) co-administration of the IL-2/IgG plasmid did not enhance CTL priming by the Gag p15/p26 plasmid, 3.) vaccinia vectors are useful for lentivirus-specific CTL induction in the horse, 4.) Gag-specific CTL alone are either insufficient or a more robust Gag-specific CTL response is needed to limit EIAV viremia and clinical disease, and 5.) CTL-inducing vaccines lacking envelope immunogens can result in lentiviral disease enhancement. Although the mechanisms for enhancement associated with this vaccine regimen remain to be elucidated, these results have important implications for development of lentivirus T cell vaccines. PMID:19368787

  3. Rapid decline in HIV viral load when introducing raltegravir-containing antiretroviral treatment late in pregnancy.

    Science.gov (United States)

    Westling, Katarina; Pettersson, Karin; Kaldma, Anneli; Navér, Lars

    2012-12-01

    Antenatal screening program for HIV has been in use in Sweden since 1987 with a 95-98% acceptance rate. Screening is performed during gestational week 10-12 and antiretroviral treatment (ART) to prevent mother-to-child transmission (MTCT) is initiated at gestational week 14-18. However, some women present with HIV in late pregnancy and additional treatment are wanted to achieve viral suppression before delivery. The integrase inhibitor raltegravir has a favorable pharmacokinetic profile and a capacity to rapidly decrease the viral load (VL). We describe four women presenting as HIV positive late in pregnancy, their ART, and outcome for the mother and child. Four women were discovered as HIV positive late in pregnancy, of 7 discovered in the antenatal screening programme in Stockholm County Council during 2011. Raltegravir was added to standard ART. The mean VL at presentation was 217,000 copies per milliliter (range, 65,000-637,000). A rapid decline of HIV RNA was observed in all cases, one woman treated with ART for only 8 days prior to delivery. The mean VL decline per week was 1.12 log (range, 0.94-1.22), which is estimated to occur (based on literature) after 1-2 months with standard ART. No side effects due to raltegravir were observed in mothers or infants. Caesarean section was performed in all cases, and the women did not breastfeed. No infant was infected. This report suggests that raltegravir added to standard antiretroviral treatment would be an option for women presenting with HIV in late pregnancy.

  4. Trends in unsafe sex and influence of viral load among patients followed since primary HIV infection, 2000-2009.

    Science.gov (United States)

    Seng, Rémonie; Rolland, Matthieu; Beck-Wirth, Geneviève; Souala, Faouzi; Deveau, Christiane; Delfraissy, Jean-François; Goujard, Cécile; Meyer, Laurence

    2011-04-24

    In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners' HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400 copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies.

  5. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...... collaboration study. METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations...... of CD4(+) cell count depletion than baseline viral load. Neither sex, race nor transmission by injecting drug use was associated with change in either the viral load or CD4(+) cell count. DISCUSSION: We found that in ART-naive individuals, viral load continues to increase over time and more sharply...

  6. Rhinovirus viremia in adult patients with high viral load in bronchoalveolar lavages.

    Science.gov (United States)

    Van Rijn, Anneloes L; Claas, Eric C; von dem Borne, Peter A; Kroes, Aloys C M; de Vries, Jutte J C

    2017-11-01

    In children, rhinovirus viremia has been associated with higher nasopharyngeal loads and increase in severity of clinical signs and symptoms. This study aims to detect rhinovirus viremia in adult patients and to establish potential correlations with the clinical course. Adult patients with rhinovirus strongly positive bronchoalveolar lavages (BAL, quantitation cycle, Cq values <25) detected between 2008 and 2014 were studied retrospectively. Blood sampled between two weeks before and two weeks after BAL sampling was tested for rhinovirus RNA. Underlying conditions, symptoms, radiography, microbiological data, and disease outcome were analysed. Twenty-seven of 43 patients with rhinovirus positive BAL at Cq values <25 had blood samples available within the prespecified time-frame (mean blood 3-4 samples per patient). Four of these 27 patients (15%) tested rhinovirus RNA positive in their blood (of whom one patient twice). Genotyping demonstrated rhinovirus A01, A24, B52 and B92 in these four immunocompromised patients. Viremic patients were not significantly different with regard to underlying conditions, respiratory symptoms, radiological findings, co-pathogens nor the number of blood samples tested for RV. However, patients with rhinovirus viremia had significant higher mortality rates compared to patients without viremia, as all four died as a consequence of respiratory problems (100%) versus 22% (5/23), p=0.007 (Fisher's exact). Rhinovirus viremia can occur in adult patients with a high viral load in BAL fluid. Rhinovirus viremia may be considered a negative prognostic factor, although a causative role with regard to the adverse outcome has yet to be demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    Directory of Open Access Journals (Sweden)

    Hyun Woong Lee

    Full Text Available Clinical manifestations of hepatitis A virus (HAV infection vary from mild to fulminant hepatic failure (FHF in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA and evaluated predictive factors for severe acute hepatitis (s-AH.We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128. Other patients were defined as mild acute hepatitis (m-AH (n = 642. Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer.In a multivariate analysis, age (HR = 1.042, P = 0.041, peak creatinine (HR = 4.014, P = 0.001, bilirubin (HR = 1.153, P = 0.003, alanine aminotransferase (ALT (HR = 1.001, P < 0.001, initial lactate dehydrogenase (LDH (HR = 1.000, P = 0.045 and total cholesterol (HR = 0.978, P < 0.001 were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100% patients with s-AH and 22/28 (78.6% patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004 and HAV RNA titer (HR = 2.076, P = 0.012 were independent factors for s-AH.Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

  8. Chitosan nanoparticles as non-viral gene delivery systems: determination of loading efficiency.

    Science.gov (United States)

    Carrillo, Carolina; Suñé, Josep Maria; Pérez-Lozano, Pilar; García-Montoya, Encarna; Sarrate, Rocío; Fàbregas, Anna; Miñarro, Montserrat; Ticó, Josep Ramon

    2014-07-01

    Chitosan has been studied for use in particle delivery systems for therapeutic purposes, since one of its most important applications is as a non-viral vector in gene therapy. Due to its positive charge, it is capable of forming DNA complexes (polyplexes) obtained through several methods and with the property of protecting nucleic acids. Two methods for obtaining the nanoparticles of chitosan-nucleic acids are reported in this study: simple complexation (of depolymerized chitosan or of different chitosan salts with plasmid) and ionic gelation (by adsorption of plasmid in the nanoparticles or by encapsulation of plasmid into nanoparticles). The determination of the loading efficiency of chitosan nanoparticles with the plasmid is carried out by electrophoretic mobility of the samples on agarose gel. Furthermore, the nanoparticles have been characterized according to their morphology, size and surface charge using AFM, TEM, laser diffraction and dynamic light scattering techniques. The polyplexes obtained have been found to be spherical and nanometric in size (between 100-230nm) with a zeta potential between 37 and 48mV. Positive results have been obtained by agarose gel electrophoresis for all studied cases: a concentration of between 20 and 30μg/mL of chitosan salts is required while for the remaining chitosan samples studied, 100% loading efficiency does not occur until a concentration equal to 100μg/mL (regardless of previous depolymerisation and the method performed). Chitosan-plasmid nanocapsules have been obtained at the polymer concentrations worked with (between 0.025 and 0.2%). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Inverse relationship between viral load and genotypic resistance mutations in Korean patients with primary HIV type 1 infections.

    Science.gov (United States)

    Chin, Bum Sik; Choi, Juyeon; Nam, Jeong-Gu; Kee, Mee Kyung; Suh, Soon Deok; Choi, Jin Young; Chu, Chaeshin; Kim, Sung Soon

    2006-11-01

    The transmission of antiretroviral-resistant HIV-1 strains is associated with suboptimal virological responses to initial antiretroviral therapy. However, certain types of resistance mutations are known to be associated with decreased viral fitness, which confers a lower replication capacity than that of the wild-type virus in the absence of antiretroviral drugs. Therefore, we evaluated the relationship between antiretroviral resistance mutations and viral replication in the primary HIV-1 infection (PHI) period. From January 2002 to March 2005, 52 PHI patients were identified in the Republic of Korea. HIV-1 RNA genotyping was performed, and the resistance mutation score was obtained from the HIV Drug Resistance Database of Stanford University. We defined the sum of the average resistance mutation scores (SARMS) for each antiretroviral drug class as a measure of the degree of resistance of any specific strain. The overall mean SARMS was 2.00 +/- 2.74, and the annual mean did not change significantly during the study period. No critical resistance mutation gene was identified in the study group. The SARMS showed a weak negative correlation with the viral load log10 during PHI, but without statistical significance (r = -0.274, p = 0.051). But the mean SARMS of patients with a viral load exceeding 100,000 copies/ml was significantly lower than that of patients with a viral load of less than 100,000 copies/ml (p = 0.03). Evaluation of the potency of antiretroviral resistance revealed a weak negative correlation with viral replication in the PHI period. This could be one reason why the transmission of resistant strains in PHI patients is not increasing significantly despite the widespread use of highly active antiretroviral therapy (HAART).

  10. Honey Bee Viruses in Wild Bees: Viral Prevalence, Loads, and Experimental Inoculation.

    Science.gov (United States)

    Dolezal, Adam G; Hendrix, Stephen D; Scavo, Nicole A; Carrillo-Tripp, Jimena; Harris, Mary A; Wheelock, M Joseph; O'Neal, Matthew E; Toth, Amy L

    2016-01-01

    Evidence of inter-species pathogen transmission from managed to wild bees has sparked concern that emerging diseases could be causing or exacerbating wild bee declines. While some pathogens, like RNA viruses, have been found in pollen and wild bees, the threat these viruses pose to wild bees is largely unknown. Here, we tested 169 bees, representing 4 families and 8 genera, for five common honey bee (Apis mellifera) viruses, finding that more than 80% of wild bees harbored at least one virus. We also quantified virus titers in these bees, providing, for the first time, an assessment of viral load in a broad spectrum of wild bees. Although virus detection was very common, virus levels in the wild bees were minimal-similar to or lower than foraging honey bees and substantially lower than honey bees collected from hives. Furthermore, when we experimentally inoculated adults of two different bee species (Megachile rotundata and Colletes inaequalis) with a mixture of common viruses that is lethal to honey bees, we saw no effect on short term survival. Overall, we found that honey bee RNA viruses can be commonly detected at low levels in many wild bee species, but we found no evidence that these pathogens cause elevated short-term mortality effects. However, more work on these viruses is greatly needed to assess effects on additional bee species and life stages.

  11. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

    Science.gov (United States)

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, Phepatitis A. PMID:26090677

  12. Global cost modeling analysis of HIV-1 and HCV viral load assays.

    Science.gov (United States)

    Elbeik, Tarek; Chen, Yi-Ming Arthur; Soutchkov, Serguei V; Loftus, Richard A; Beringer, Scott

    2003-08-01

    This review addresses hidden costs associated with the Bayer VERSANT assay, Roche AMPLICOR MONITOR test and COBAS AMPLICOR MONITOR test and how these influence the final per reportable cost to a testing laboratory in resource-rich and -poor countries. An in-depth evaluation and recommendation of the most cost-effective approach for these tests is presented. The analyses demonstrate the need for manufacturers to consider labor and supply costs when marketing a kit in resource-poor countries, noting that marketing strategies need to change. In the absence of any proven monitoring alternative, emphasis is placed on increasing market share to promote significant reduction in kit prices to suit the demands of markets in resource-poor countries. Finally, recommendations are made to improve the overall cost structure of viral load testing. This review is intended as a tool to optimize assay usage in attaining the lowest performance costs by assay and is not to endorse any test, as will become apparent.

  13. Post-Weaning Breast Milk HIV-1 Viral Load, Blood Prolactin Levels and Breast Milk Volume

    Science.gov (United States)

    Thea, Donald M.; Aldrovandi, Grace; Kankasa, Chipepo; Kasonde, Prisca; Decker, W. Donald; Semrau, Katherine; Sinkala, Moses; Kuhn, Louise

    2006-01-01

    Background: The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-exposed children, on the quantity of HIV viral load in breast milk (BMVL) is not known. Objectives: To determine the effect of abrupt cessation of breastfeeding on serum prolactin, pumped breast milk volume and BMVL obtained 2 weeks after rapid weaning in HIV-infected women. Methods: Women enrolled in a prospective study (ZEBS) were randomized to abruptly wean at 20 weeks postpartum or continue exclusive breastfeeding. Breast milk was obtained at 22 weeks by electric breast pump over 10 min from 222 women who had either weaned or continued to breastfeed. Pre- and post-pumping prolactin was measured. BMVL was measured at 20 and 22 weeks in 71 randomly selected women from both groups. Results: Baseline prolactin and breast milk volume was significantly lower among women who had weaned. Detectable (68 versus 42%; P 0.03) and median BMVL (448 versus < 50 copies/ml; P = 0.005) was significantly higher = among those who had weaned in comparison with those who were still breastfeeding and was significantly higher in the same women after weaning compared with 2 weeks earlier (P = 0.001). Conclusions: BMVL is substantially higher after rapid weaning and this may pose an increased risk of HIV transmission if children resume breastfeeding after a period of cessation. Increases in BMVL with differing degrees of mixed feeding needs to be assessed. PMID:16847409

  14. Anthropogenic Viral Load on the Sources of Water in Kryvyi Rig

    Directory of Open Access Journals (Sweden)

    N.S. Prus

    2016-04-01

    Full Text Available The aim of the study was to determine the hepatropic viruses load on the natural sources of wastewater use of the industrial region. Methods. We investigated open water samples from places of water intake, which is later purified and used in consumer’s drinking purposes; river water samples in resting places and samples of sewage from discharge to the environment places. We used EUSA method using sets of reagents for the detection of antigen of hepatitis A virus (HAV HAV-antigen ELISA-Best (Russia, devices for the automatic washing of microplates and automatic record of the results using the immunoassay analyzer StatFax303 (Awareness Technology Inc., USA. Results. During 2000–2015 three peaks of the indication of HAV antigens’ rise in river water and sewage samples were noted. In 2002–2003 in average 34.4 and 32.3 % of the sewage and river water samples were positive, in 2008 26.7 and 27.1 %, respectively. The third peak of HAV antigen detection in open water was observed in 2012, only 17.8 %. Wastewater has been losing viral antigens since 2008, in fact to 0 % in 2013–2014. Conclusions. Aquatic ecosystem pollution by biological components occurs despite of primary treatment of wastewater. Drinking water contamination, which is used in everyday life, probably can be linked to an unsatisfactory condition of pipelines and laying of sewage supply.

  15. Antiretroviral treatment adherence as a mediating factor between psychosocial variables and HIV viral load.

    Science.gov (United States)

    Attonito, Jennifer; Dévieux, Jessy G; Lerner, Brenda D G; Hospital, Michelle M; Rosenberg, Rhonda

    2014-01-01

    Psychosocial factors may directly impact HIV health measures such as viral load (VL) whether or not patients are taking antiretroviral treatment (ART) consistently. Structural equation modeling plus Baron and Kenny's (1986) four-step approach were used to test a mediated model predicting VL among 246 HIV-infected adults who were on ART. Exogenous variables were social support, barriers to adherence, and stress. Moderators were alcohol use, marijuana use, and neurocognitive impairment. A small positive association between marijuana use and ART adherence approached significance. Only barriers to adherence predicted a decrease in adherence rates and an increase in VL. No other factors were significantly associated with either VL or adherence, and no interaction effects between exogenous variables and moderators were identified. The association between barriers to adherence and VL was partially mediated by ART adherence. Findings provide modest support for a direct link between psychosocial variables and a virologic response to ART. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  16. Diagnosis, gB genotype distribution and viral load of symptomatic congenitally infected CMV patients in Cuba.

    Science.gov (United States)

    Correa, C; Kourí, V; Pérez, L; Soto, Y; Limia, C

    2016-10-01

    Cytomegalovirus (CMV) is the leading cause of viral congenital infection. Some viral factors have been proposed to be CMV pathogenicity markers. The objective of this study was to investigate the frequency of congenital CMV infection in symptomatic patients and the possible association with the CMV glycoprotein B (gB) genotype and viral load. A total of 361 newborns (NB) and 158 pregnant women (PW) with clinically suspected CMV infection were enrolled. Studied samples included urine, saliva, serum, vaginal swabs and amniotic fluid. CMV infection was diagnosed by multiplex nested PCR. CMV gB genotyping was performed on infected samples, followed by viral load determination. Overall, 18.7% of the tested patients were positive for CMV infection, 19.7% of NB were congenitally infected and 16.5% of PW showed active CMV infection. gB-2 was the most prevalent genotype detected (39/97 patients). gB CMV mixed infections were detected in 12 patients. gB-2 was associated with mono-infections (PCMV load was statistically significant among patients presenting different clinical signs (P=0.04). This study showed that CMV is a frequent cause of congenital infection in symptomatic Cuban patients. Despite gB2 being the most frequently detected, gB-4 was the only genotype associated with clinical features (sepsis-like syndrome in NB). No other associations among specific genotypes and clinical characteristics were found. Further studies are needed to clarify the role that viral load and genotype play in the outcome of congenital infection.

  17. Improving Site Characterization for Rock Dredging using a Drilling Parameter Recorder and the Point Load Test

    Science.gov (United States)

    1994-09-01

    after Bieniawski (1975)) ............................... 31 Figure 20. Core sample showing local crushing failure at the point load platens...Saluja 1974) and joint strength ( Bieniawski 1974) are less for saturated conditions. Additionally, because dredges excavate rock from a floating plant...the Brazilian tensile test strength ( Bieniawski 1975, Wijk 1980). Accordingly, correlation of point load strength with unconfined compressive strength

  18. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

    Directory of Open Access Journals (Sweden)

    Sharma Gaurav

    2011-01-01

    Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.

  19. Genotype distribution, viral load and clinical characteristics of infants with postnatal or congenital cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Joppe Nijman

    Full Text Available Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection.The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity.Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003-2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution.Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2-8 years. The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups.Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible

  20. Genotype distribution, viral load and clinical characteristics of infants with postnatal or congenital cytomegalovirus infection.

    Science.gov (United States)

    Nijman, Joppe; Mandemaker, Femke S; Verboon-Maciolek, Malgorzata A; Aitken, Susan C; van Loon, Anton M; de Vries, Linda S; Schuurman, Rob

    2014-01-01

    Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection. The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity. Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003-2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution. Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2-8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups. Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the

  1. Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

    Science.gov (United States)

    Coleman, Hannah N; Greenfield, William W; Stratton, Shawna L; Vaughn, Rita; Kieber, Alexander; Moerman-Herzog, Andrea M; Spencer, Horace J; Hitt, Wilbur C; Quick, Charles Matthew; Hutchins, Laura F; Mackintosh, Samuel G; Edmondson, Ricky D; Erickson, Stephen W; Nakagawa, Mayumi

    2016-05-01

    In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 μg per peptide dose, the 50 μg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50% at the 50 μg dose (7 of 14) and 100 μg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened.

  2. Systematic review of the performance of HIV viral load technologies on plasma samples.

    Science.gov (United States)

    Sollis, Kimberly A; Smit, Pieter W; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perrins, Jos; Peeling, Rosanna W

    2014-01-01

    Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1%) and 5.44% (range 1.17-30.00%) across the range of VL counts (2log10-7log10). This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of

  3. Membrane Bioreactor-Based Wastewater Treatment Plant in Saudi Arabia: Reduction of Viral Diversity, Load, and Infectious Capacity

    KAUST Repository

    Jumat, Muhammad

    2017-07-18

    A membrane bioreactor (MBR)-based wastewater treatment plant in Saudi Arabia was assessed over a nine-month period for virus removal efficiency. Viral diversity was detected using omics-based approaches. Log reduction values (LRV) of Adenoviruses (AdV) and Enteroviruses (EV) were enumerated using digital polymerase chain reaction (dPCR) and assessed for infectivity using fluorescence-based infection assays. MBR treatment was successful in reducing viral diversity. Plant viruses remained abundant in the treated effluent. Human enteric viruses were present in lower abundance than plant viruses, and were reduced by MBR at varying LRV. AdV copy numbers were reduced by 3.7-log. Infectious AdV was not detected in the effluent. EV copy numbers were reduced by 1.7-log post MBR and infectious EV decreased by an average of 2.0-log. Infectious EV was detected in the chlorinated effluent, occasionally in concentrations that approximate to its 50% infectious dose. Overall, results indicated that a MBR-based wastewater treatment plant (WWTP) effectively reduces viral diversity, viral load, and infectious capacity by up to 4-logs. These findings suggest potential concerns associated with plant and human enteric viruses for reuse events in this country. Local guidelines for assessment of treated water quality should take into consideration both infectious viral concentration and LRV.

  4. Prevalence of oral lesions in HIV patients related to CD4 cell count and viral load in a Venezuelan population.

    Science.gov (United States)

    Bravo, Inés María; Correnti, María; Escalona, Laura; Perrone, Marianella; Brito, Aubert; Tovar, Vilma; Rivera, Helen

    2006-01-01

    To determine the prevalence of oral lesions in a HIV+ group of patients, related to CD4 cell count and viral load in a Venezuelan population. In the present study, we evaluated 75 HIV+ adult patients, attended at the Center of Infectious Diseases, at the Faculty of Dentistry, Central University of Venezuela. Each patient was clinically examined for detection of oral mucosal lesions. In addition, CD4 cell count was determined by flow cytometry, as well as viral load by RT-PCR (Amplicor HIV-RNA, TM test 1.5, Roche). 85% (64/75) of HIV/AIDS patients showed associated HIV lesions. Oral Candidiasis constituted the most common lesion representing a 61% (39/64), followed by Oral Hairy Leukoplakia 53% (34/64); Oral Leukoplakia 34% (22/64), Melanic Hyperpigmentation 38% (18/64); Papilloma 13 (6/64), Lineal Gingival Erythema 8% (5/64); Aphtous Recurrent Stomatitis 5% (4/64) and Kaposi's Sarcoma 5% (3/64). Only one case of the following lesions were represented by Non Hodgkin Lymphoma, Multifocal Epithelial Hyperplasia, Recurrent Herpes, Histoplasmosis and Molluscum Contagiosum. The patients with a viral load of 30.000 copies/mm3 exhibited oral lesions related with HIV, independent of CD4 cell count, although patients with CD4+ levels of 200 cel/mm3 were more susceptible to develop these lesions. The most common oral lesion was Oral Candidiasis followed by Oral Hairy Leukoplakia, Oral Leukoplakia and Melanic Hyperpigmentation. A high viral load was strongly associated to the oral lesions occurrence independently of CD4+ cell count.

  5. Effects of medical male circumcision (MC on plasma HIV viral load in HIV+ HAART naïve men; Rakai, Uganda.

    Directory of Open Access Journals (Sweden)

    Godfrey Kigozi

    Full Text Available BACKGROUND: Medical male circumcision (MC of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. METHODS: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE. RESULTS: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005. Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef.  = -0.134, p<0.001. CONCLUSION: We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.

  6. A robust HIV-1 viral load detection assay optimized for Indian sub type C specific strains and resource limiting setting

    Directory of Open Access Journals (Sweden)

    Arpan Acharya

    2014-01-01

    Full Text Available BACKGROUND: Human Immunodeficiency Virus Type 1 (HIV-1 viral load testing at regular intervals is an integral component of disease management in Acquired Immunodeficiency Syndrome (AIDS patients. The need in countries like India is therefore an assay that is not only economical but efficient and highly specific for HIV-1 sub type C virus. This study reports a SYBR Green-based HIV-1 real time PCR assay for viral load testing and is designed for enhanced specificity towards HIV-1 sub type C viruses prevalent in India. RESULTS: Linear regression of the observed and reference concentration of standards used in this study generated a correlation coefficient of 0.998 (p 0.5 log value, a figure that is considered clinically significant by physicians. CONCLUSION: The HIV-1 viral load assay reported in this study was found to be robust, reliable, economical and effective in resource limited settings such as those existing in India. PCR probes specially designed from HIV-1 Subtype C-specific nucleotide sequences originating from India imparted specificity towards such isolates and demonstrated superior results when compared to two similar commercial assays widely used in India.

  7. Predictors of undetectable plasma viral load in HIV-positive adults receiving antiretroviral therapy in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Marysabel Pinto Telis Silveira

    Full Text Available Factors associated with undetectable viral load ( or = 95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73-9,53, compared with less than 60% adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95% 1.09-10.46; and smaller for viral load previous to adherence measurement > or = 5.2 log10 (OR = 0.19; CI95% 0.06-0.58, adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.

  8. Reduction Assessment of Agricultural Non-Point Source Pollutant Loading

    OpenAIRE

    Fu, YiCheng; Zang, Wenbin; Zhang, Jian; Wang, Hongtao; Zhang, Chunling; Shi, Wanli

    2018-01-01

    NPS (Non-point source) pollution has become a key impact element to watershed environment at present. With the development of technology, application of models to control NPS pollution has become a very common practice for resource management and Pollutant reduction control in the watershed scale of China. The SWAT (Soil and Water Assessment Tool) model is a semi-conceptual model, which was put forward to estimate pollutant production & the influences on water quantity-quality under different...

  9. Long-term outcome of telbivudine versus entecavir in treating higher viral load chronic hepatitis B patients without cirrhosis.

    Science.gov (United States)

    Pan, H-Y; Pan, H-Y; Song, W-Y; Zheng, W; Tong, Y-X; Yang, D-H; Dai, Y-N; Chen, M-J; Wang, M-S; Huang, Y-C; Zhang, J-J; Huang, H-J

    2017-11-01

    Chronic hepatitis B (CHB) patients with higher hepatitis B virus (HBV) load (higher viral load [HVL], HBV DNA ≥1 × 10 7 copies/mL) require antiviral therapy, but data for evaluating the long-term outcome of this therapy with antiviral agents remain limited. We comparatively evaluated the efficacy and the safety of nucleoside analogues in 179 noncirrhotic CHB patients with HVL over 5 years. The HBeAg-positive (n = 104) or HBeAg-negative (n = 75) patients were treated consecutively with telbivudine (LdT, n = 88) or entecavir (ETV, n = 91) and evaluated for viral response, drug resistance and safety. HBV DNA, viral serology, biochemistries, HBV mutation and off-therapy relapse were determined. The cumulative rates of HBV DNA negativity were 86.4% and 94.5% for LdT and ETV at year 5, respectively. The rates of early viral response (EVR, HBV DNA loss-seroconversions were 47.7% and 18.2% on LdT and 16.5% and 2.2% on ETV (P loss-seroconversion, followed by 33 ± 4.6 month off-therapy without a relapse. Viral mutations and serum creatine kinase elevation were 9.1% and 8.0% on LdT, but only 1.1% and 0% on ETV. Both LdT and ETV suppressed HBV replication in HVL CHB patients within 5 years. LdT therapy achieved a higher EVR, HBeAg and HBsAg seroconversion, especially in the younger patients, whereas ETV caused lower drug resistance and fewer adverse events. This finding might help to identify the optimal treatment for CHB patients with HVL. © 2017 John Wiley & Sons Ltd.

  10. Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages

    Directory of Open Access Journals (Sweden)

    Yuqing Gong

    2017-12-01

    Conclusions: PLGA-based EVG nanoformulation increased the intracellular uptake of EVG, as well as enhanced viral suppression in HIV-infected macrophages, suggesting its potential for improved HIV treatment in monocytic cells.

  11. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

    Directory of Open Access Journals (Sweden)

    Paul D Griffiths

    Full Text Available To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml of whole blood.Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A. A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml or less than 3000 genomes/ml were obtained (Part B. For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56% in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37% in the immediate treatment arm (p = 0.193. However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022. In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35% in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45% among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322. However, the duration of antiviral treatment was significantly shorter (p = 0.0012 in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.

  12. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H

    2008-01-01

    BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequences...... strategies-based on viral load, CD4 cell count, or clinical observation alone-for determining when to switch people starting antiretroviral treatment with the WHO-recommended first-line regimen of stavudine, lamivudine, and nevirapine to second-line antiretroviral treatment. FINDINGS: Over 5 years......, the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur...

  13. Reducing uncertainty in within-host parameter estimates of influenza infection by measuring both infectious and total viral load.

    Directory of Open Access Journals (Sweden)

    Stephen M Petrie

    Full Text Available For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID50 are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID50 and total (via rRT-PCR viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID50 data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the "dual-measurement" model are similar to those from the TCID50-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID50 assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics.

  14. The effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status: a randomized trial among chronic hepatitis C virus-infected patients

    DEFF Research Database (Denmark)

    Groenbaek, K.; Friis, H.; Hansen, Max

    2006-01-01

    Objective To assess the effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status. Methods We performed a randomized, placebo-controlled, double-blind trial to assess the effect of antioxidant supplementation on serum alanine aminotransferase, plasma hepa...... and catalase) or plasma levels of oxidative markers (malondialdehyde and 2-amino-adipic semialdehyde) were found. Conclusion Supplementation with vitamin C, E and selenium increased the antioxidant status, but had no effects on alanine aminotransferase, viral load or oxidative markers....

  15. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Phillips, Andrew N; Gatell, Jose

    2013-01-01

    CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to ...... was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals....

  16. Challenges with targeted viral load testing for medical inpatients at Queen Elizabeth Central Hospital in Blantyre, Malawi.

    Science.gov (United States)

    Craik, Alison; Patel, Priyanka; Patel, Pratiksha; Mallewa, Jane; Malisita, Ken; Bitilinyu-Bangoh, Joseph; van Oosterhout, Joep J; Kelly, Christine

    2016-12-01

    Approximately 75% of medical inpatients at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi are HIV seropositive, and a third of these patients are on antiretroviral therapy (ART). Malawi guidelines recommend targeted viral load (VL) testing for patients on ART for at least one year who report excellent adherence and present with a WHO clinical stage 3 or 4 HIV disease. A switch to second-line ART is only indicated if a VL result >5000 copies/mL confirms treatment failure. During an audit of targeted VL testing at QECH, all adult medical admissions were screened to identify those in need of VL testing. Daily review of inpatient notes ascertained whether VL testing was ordered and carried out. At 8 weeks post-discharge the laboratory database was checked for results and was triangulated with the HIV outpatient database to ascertain whether patients had attended clinic, received results, and if these results had been acted upon. Out of 81 patients recruited, 63 (77%) had a VL requested. At 8 weeks post-discharge, nine patients (14%) had VL results available. The median (IQR) waiting time for those with results was 29 days (20-47). Five patients had a VL >5000 copies/mL. Of these patients, three attended clinic and one was switched to second-line ART. Of the remaining 55 patients awaiting results, the median (IQR) waiting time at the 8-week follow-up point was 72 days (67-80). At 8 weeks post-discharge, 8 patients (33%) had died. Our findings demonstrate challenges with targeted VL testing at QECH. Only two-thirds of patients with clinical ART failure were identified as eligible for targeted VL testing, and of these less than one-sixth had VL results available after 8 weeks. Interventions such as point-of-care targeted VL testing could result in faster turnaround times. In the interim, we suggest further evaluation of the possibility of switching patients with clinical ART failure and a low CD4 count to second-line ART while awaiting VL results.

  17. KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians.

    Directory of Open Access Journals (Sweden)

    Louis-Marie Yindom

    Full Text Available Hepatocellular carcinoma (HCC causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV and C (HCV viruses. Natural Killer (NK cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR. Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation. HBV is highly prevalent in The Gambia and the commonest cause of liver disease. The Gambia Liver Cancer Study was a matched case-control study conducted between September 1997 and January 2001 where cases with liver disease were identified in three tertiary referral hospitals and matched with out-patient controls with no clinical evidence of liver disease.We typed 15 KIR genes using the polymerase chain reaction with sequence specific primers (PCR-SSP in 279 adult Gambians, 136 with liver disease (HCC or Cirrhosis and 143 matched controls. We investigated effects of KIR genotypes and haplotypes on HBV infection and associations with cirrhosis and HCC.Homozygosity for KIR group A gene-content haplotype was associated with HBsAg carriage (OR 3.7, 95% CI 1.4-10.0 whilst telomeric A genotype (t-AA was associated with reduced risk of e antigenaemia (OR 0.2, 95% CI 0.0-0.6 and lower viral loads (mean log viral load 5.2 vs. 6.9, pc = 0.022. One novel telomeric B genotype (t-ABx2 containing KIR3DS1 (which is rare in West Africa was also linked to e antigenaemia (OR 8.8, 95% CI 1.3-60.5. There were no associations with cirrhosis or HCC.Certain KIR profiles may promote clearance of hepatitis B surface antigen whilst others predispose to e antigen carriage and high viral load. Larger studies are necessary to quantify the effects of individual KIR genes, haplotypes and KIR/HLA combinations on long

  18. KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians.

    Science.gov (United States)

    Yindom, Louis-Marie; Mendy, Maimuna; Bodimeade, Christopher; Chambion, Caroline; Aka, Peter; Whittle, Hilton C; Rowland-Jones, Sarah L; Walton, Robert

    2017-01-01

    Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation. HBV is highly prevalent in The Gambia and the commonest cause of liver disease. The Gambia Liver Cancer Study was a matched case-control study conducted between September 1997 and January 2001 where cases with liver disease were identified in three tertiary referral hospitals and matched with out-patient controls with no clinical evidence of liver disease. We typed 15 KIR genes using the polymerase chain reaction with sequence specific primers (PCR-SSP) in 279 adult Gambians, 136 with liver disease (HCC or Cirrhosis) and 143 matched controls. We investigated effects of KIR genotypes and haplotypes on HBV infection and associations with cirrhosis and HCC. Homozygosity for KIR group A gene-content haplotype was associated with HBsAg carriage (OR 3.7, 95% CI 1.4-10.0) whilst telomeric A genotype (t-AA) was associated with reduced risk of e antigenaemia (OR 0.2, 95% CI 0.0-0.6) and lower viral loads (mean log viral load 5.2 vs. 6.9, pc = 0.022). One novel telomeric B genotype (t-ABx2) containing KIR3DS1 (which is rare in West Africa) was also linked to e antigenaemia (OR 8.8, 95% CI 1.3-60.5). There were no associations with cirrhosis or HCC. Certain KIR profiles may promote clearance of hepatitis B surface antigen whilst others predispose to e antigen carriage and high viral load. Larger studies are necessary to quantify the effects of individual KIR genes, haplotypes and KIR/HLA combinations on long

  19. High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

    Science.gov (United States)

    Farquhar, Carey; Nduati, Ruth; Haigwood, Nancy; Sutton, William; Mbori-Ngacha, Dorothy; Richardson, Barbra; John-Stewart, Grace

    2012-01-01

    Background Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. Methods To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Results Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). Conclusions This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants. PMID:16280707

  20. Accuracy of self-report of HIV viral load among people with HIV on antiretroviral treatment.

    Science.gov (United States)

    Sewell, J; Daskalopoulou, M; Nakagawa, F; Lampe, F C; Edwards, S; Perry, N; Wilkins, E; O'Connell, R; Jones, M; Collins, S; Speakman, A; Phillips, A N; Rodger, A J

    2017-08-01

    The aim of the study was to assess, among people living with HIV, knowledge of their latest HIV viral load (VL) and CD4 count. Agreement between self-report and clinic record was assessed among 2771 HIV-diagnosed individuals on antiretroviral treatment (ART) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes Study (2011-2012). A confidential self-completed questionnaire collected information on demographic, socioeconomic, HIV-related and health-related factors. Participants were asked to self-report their latest VL [undetectable (≤ 50 copies/mL), detectable (> 50 copies/mL) or "don't know"] and CD4 count ( 500 cells/μL, or "don't know"). Latest clinic-recorded VL and CD4 count were documented. Of 2678 participants on ART, 434 (16.2%) did not accurately report whether their VL was undetectable. Of 2334 participants with clinic-recorded VL ≤ 50 copies/mL, 2061 (88.3%) correctly reported undetectable VL; 49 (2.1%) reported detectable VL; 224 (9.6%) did not know their VL. Of 344 participants with clinic-recorded VL > 50 copies/mL, 183 (53.2%) correctly reported detectable VL; 76 (22.1%) reported undetectable VL; 85 (24.7%) did not know their VL. Of 2137 participants who reported undetectable VL, clinic-recorded VL was ≤ 50 copies/mL for 2061 (96.4%) and self-report of VL (including "don't know") included socioeconomic disadvantage [prevalence ratio (95% CI) for "not" vs. "always" having enough money for basic needs: 2.4 (1.9, 3.1)], poor English fluency [3.5 (2.4, 5.1) vs. UK born], nondisclosure of HIV status [1.7 (1.3, 2.1)], ART nonadherence [2.1 (1.7, 2.7) for three or more missed doses vs. none in the past 2 weeks] and depressive symptoms (PHQ-9 score ≥ 10) [1.9 (1.6, 2.2)]. Overall, 612 (22.9%) of 2667 participants on ART did not accurately self-report whether or not their CD4 count was ≤ 350 cells/μL. There is a high level of accuracy of a self-report of undetectable VL in people on ART in the UK. Overall, accurate knowledge of

  1. Wireless power charging using point of load controlled high frequency power converters

    Science.gov (United States)

    Miller, John M.; Campbell, Steven L.; Chambon, Paul H.; Seiber, Larry E.; White, Clifford P.

    2015-10-13

    An apparatus for wirelessly charging a battery of an electric vehicle is provided with a point of load control. The apparatus includes a base unit for generating a direct current (DC) voltage. The base unit is regulated by a power level controller. One or more point of load converters can be connected to the base unit by a conductor, with each point of load converter comprising a control signal generator that transmits a signal to the power level controller. The output power level of the DC voltage provided by the base unit is controlled by power level controller such that the power level is sufficient to power all active load converters when commanded to do so by any of the active controllers, without generating excessive power that may be otherwise wasted.

  2. Maternal plasma viral load and neutralizing/enhancing antibodies in vertical transmission of HIV: A non-randomized prospective study

    Directory of Open Access Journals (Sweden)

    Weiss Heidi

    2005-02-01

    Full Text Available Abstract Background We examined the association and interaction between maternal viral load and antibodies in vertical transmission of HIV in a non-randomized prospective study of 43 HIV-1 infected pregnant women who attended the San Juan City Hospital, Puerto Rico, and their 45 newborn infants. The women and infants received antiretroviral therapy. Methods A nested PCR assay of the HIV-1 envelope V3 region and infant PBMC culture were performed to determine HIV status of the infants. Maternal and infant plasma were tested for HIV neutralization or enhancement in monocyte-derived macrophages. Results Twelve (26.7% infants were positive by the HIV V3 PCR assay and 3 of the 12 were also positive by culture. There was a trend of agreement between high maternal viral load and HIV transmission by multivariate analysis (OR = 2.5, CI = 0.92, p = 0.0681. Both maternal and infant plasma significantly (p = 0.001 for both reduced HIV replication at 10-1 dilution compared with HIV negative plasma. Infant plasma neutralized HIV (p = 0.001 at 10-2 dilution but maternal plasma lost neutralizing effect at this dilution. At 10-3 dilution both maternal and infant plasma increased virus replication above that obtained with HIV negative plasma but only the increase by maternal plasma was statistically significant (p = 0.005. There were good agreements in enhancing activity in plasma between mother-infant pairs, but there was no significant association between HIV enhancement by maternal plasma and vertical transmission. Conclusion Although not statistically significant, the trend of association between maternal viral load and maternal-infant transmission of HIV supports the finding that viral load is a predictor of maternal-infant transmission. Both maternal and infant plasma neutralized HIV at low dilution and enhanced virus replication at high dilution. The antiretroviral treatments that the women received and the small sample size may have contributed to the

  3. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus.

    Science.gov (United States)

    Mealey, Robert H; Zhang, Baoshan; Leib, Steven R; Littke, Matt H; McGuire, Travis C

    2003-09-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined.

  4. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2003-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  5. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    Science.gov (United States)

    Mealey, Robert H.; Zhang, Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2012-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined. PMID:12954220

  6. Method of nuclear reactor control using a variable temperature load dependent set point

    International Nuclear Information System (INIS)

    Kelly, J.J.; Rambo, G.E.

    1982-01-01

    A method and apparatus for controlling a nuclear reactor in response to a variable average reactor coolant temperature set point is disclosed. The set point is dependent upon percent of full power load demand. A manually-actuated ''droop mode'' of control is provided whereby the reactor coolant temperature is allowed to drop below the set point temperature a predetermined amount wherein the control is switched from reactor control rods exclusively to feedwater flow

  7. Innovative technologies for point-of-care testing of viral hepatitis in low-resource and decentralized settings.

    Science.gov (United States)

    Duchesne, L; Lacombe, K

    2018-02-01

    According to the Global Burden of Diseases, chronic viral hepatitis B and C are one of the most challenging global health conditions that rank among the first causes of morbidity and mortality worldwide. Low- and middle-income countries are particularly affected by the health burden associated with HBV or HCV infection. One major gap in efficiently addressing the issue of viral hepatitis is universal screening. However, the costs and chronic lack of human resources for using traditional screening strategies based on serology and molecular biology preclude any scaling-up. Point-of-care tests have been deemed a powerful potential solution to fill the current diagnostics gap in low-resource and decentralized settings. Despite high interest resulting from their development in recent years, very few point-of-care devices have reached the market. Scaling down and automating all testing steps in 1 single device (eg, sample preparation, detection and readout) is indeed challenging. But innovations in multiple disciplines such as nanotechnologies, microfluidics, biosensors and synthetic biology have led to the creation of chip-sized laboratory systems called "lab-on-a-chip" devices. This review aims to explain how these innovations can overcome technological barriers that usually arise for each testing step while developing integrated point-of-care tests. Point-of-care test prototypes rarely meet the requirements for mass production, which also hinders their large-scale production. In addition to logistical hurdles, legal and economic constraints specific to the commercialization of in vitro diagnostics, which have also participated in the low transfer of innovative point-of-care tests to the field, are discussed. © 2017 John Wiley & Sons Ltd.

  8. A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots.

    Science.gov (United States)

    Makadzange, A Tariro; Boyd, F Kathryn; Chimukangara, Benjamin; Masimirembwa, Collen; Katzenstein, David; Ndhlovu, Chiratidzo E

    2017-07-01

    Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system. Copyright © 2017 Makadzange et al.

  9. Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus

    Science.gov (United States)

    Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.

    2012-01-01

    Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

  10. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD.

    Science.gov (United States)

    Contoli, Marco; Pauletti, Alessia; Rossi, Maria Rita; Spanevello, Antonio; Casolari, Paolo; Marcellini, Andrea; Forini, Giacomo; Gnesini, Giulia; Marku, Brunilda; Barnes, Neil; Rizzi, Andrea; Curradi, Giacomo; Caramori, Gaetano; Morelli, Paolo; Papi, Alberto

    2017-10-01

    Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections . The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load. Copyright ©ERS 2017.

  11. [Effects of traditional Chinese medicine on CD4 + T cell counts and HIV viral loads during structured treatment interruption in highly active antiretroviral therapy].

    Science.gov (United States)

    Zhao, Hong-xin; Zhang, Fu-jie; Han, Ning; Lan, Meng-dong; Yao, Jun; Liu, Zhi-ying; Lu, Lian-he; Wei, Hong-shan

    2006-10-01

    To explore the impacts of traditional Chinese medicine (TCM) on CD4 + T cell counts and human immunodeficiency virus (HIV) viral loads during the course of structured treatment interruption (STI) in highly active antiretroviral therapy (HAART). Nineteen HIV/ADIS patients were treated for 14 months as follows: initiated with zidovudine/lamivudine + efavirdine for 6 months, then discontinued the therapy and treated with TCM instead for 2 months. HAART was then reinitiated for another 3 months, and then discontinued and replaced with TCM for another 3 months. The changes of CD4 + T cell counts and HIV viral loads were measured. During the first STI of HAART, 43.8% of patients had no viral rebounds one month later, and 62.6% had stable or increased immune functions; 18.8% had no viral rebounds two months later, and 43.8% had stable or increased immune functions. Changes of viral loads were not significantly different between these two months (P = 0.097), while CD4 + T cell counts significantly decreased two months later compared with one month later (P = 0.043). During the second STI of HAART, 33.3% of patients had no viral rebounds one month later, and 64.3% had stable or increased immune functions; 13.3% had no viral rebounds 3 months later and 46.6% had stable or increased immune functions. Changes of viral loads had significant difference (P = 0. 017), while CD4 + T cell counts at month 12 elevated significantly compared with the baseline (P = 0.014). TCM can suppress the viral rebounds during STI-HAART, maintain immune functions. However, this effect may decrease along with the prolongation of STI-HAART.

  12. Point mutation flanking a CTL epitope ablates in vitro and in vivo recognition of a full-length viral protein.

    Science.gov (United States)

    Yellen-Shaw, A J; Wherry, E J; Dubois, G C; Eisenlohr, L C

    1997-04-01

    CD8+ T cells (T(CD8+)) recognize viral Ags as short peptides (epitopes) displayed at the cell surface by MHC class I molecules. Using a panel of recombinant vaccinia viruses, we show that single-point mutations flanking either side of an H-2Kd-restricted epitope, residues 147-155, within full-length influenza nucleoprotein (NP) can impact, even ablate, presentation of that epitope, while having no effect on presentation of distal epitopes. The most severe blocking mutation (Ala to Pro at position 146) did not inhibit NP(147-155) presentation in the context of a truncated minigene, implying that this peptide is not a functional processing intermediate. An amino-terminal proline replacement also significantly reduced presentation of NP(50-57) (H-2Kk restricted), while the same mutation did not affect a third NP epitope. Thus, while trends in processing specificity may exist, the epitope itself contributes to flanking sequence effects. These findings were paralleled by in vivo priming experiments in which, depending on viral dose, subtle in vitro blocking effects were absolute. Proteasome/synthetic peptide coincubation studies support a role for enhanced epitope destruction in preventing presentation, as did the effect of the peptide aldehyde, LLnL, which restored presentation of NP(147-155) from the mutated constructs. This reagent did not inhibit epitope presentation, even from wild-type NP, suggesting that its production may be proteasome independent. These results support the notion that point mutation of epitope flanking sequence can serve as a mechanism for viral immune evasion, shed light on the mechanisms involved, and suggest that in vitro assays may not be sensitive indicators of flanking sequence effects.

  13. Experimental and Theoretical Deflections of Hybrid Composite Sandwich Panel under Four-point Bending Load

    Directory of Open Access Journals (Sweden)

    Jauhar Fajrin

    2017-03-01

    Full Text Available This paper presents a comparison of theoretical and experimental deflection of a hybrid sandwich panel under four-point bending load. The paper initially presents few basic equations developed under three-point load, followed by development of model under four-point bending load and a comparative analysis between theoretical and experimental results. It was found that the proposed model for predicting the deflection of hybrid sandwich panels provided fair agreement with the experimental values. Most of the sandwich panels showed theoretical deflection values higher than the experimental values, which is desirable in the design. It was also noticed that the introduction of intermediate layer does not contribute much to reduce the deflection of sandwich panel as the main contributor for the total deflection was the shear deformation of the core that mostly determined by the geometric of the samples and the thickness of the core.

  14. Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C.

    Science.gov (United States)

    Fernandes-Cardoso, Juliana; Süffert, Theodoro Armando; Correa, Maria da Gloria; Jobim, Luiz Fernando Job; Jobim, Mariana; Salim, Patricia Hartstein; Arruda, Monica Barcelos; Boullosa, Lidia Theodoro; Tanuri, Amilcar; Porto, Luis Cristóvão; Ferreira, Orlando C

    2016-10-01

    There is a great variety of HIV-1 subtypes circulating in Brazil, including subtype C, whose prevalence is on the rise, particularly in the southern region. Many host and viral genetic factors may be involved in this trend. We evaluated the influence of human leukocyte antigen (HLA) class I alleles and killer-cell immunoglobulin-like receptor (KIR) genotypes on viral set point and T-CD4(+) parameters in 84 treatment-naïve HIV-1-positive individuals. Frequency data in the infected group were compared to data of 548 healthy control subjects. Individuals with the KIR AA genotype had a higher viral load (VL) than individuals with the KIR Bx genotype. The HIV-1 group was subdivided into three subgroups according to HLA-B allele presence: those with protection to disease alleles (HLA-B(+)), accelerated disease progression alleles (HLA-B(-)), or neither (HLA-B(o)) were grouped. We observed a significant effect of the HLA-B allele presence on VL. The HLA-B(+) group had significantly lower VL than the HLA-B(-) group and trended toward a lower VL than the HLA-B(o) group. There were significant differences between groups expressing extreme VL values: KIR-AA+HLA-B(-) vs. KIR Bx+HLA-B(+) and KIR-AA+HLA-B(o)vs. KIR Bx+HLA-B(+). The relationship of KIR/HLA host genetics with slow HIV disease progression in southern Brazil may be useful for vaccine developers, epidemiologists, and clinicians. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Evaluating adherence to highly active antiretroviral therapy with use of pill counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique.

    Science.gov (United States)

    San Lio, Massimo Magnano; Carbini, Riccardo; Germano, Paola; Guidotti, Giovanni; Mancinelli, Sandro; Magid, Noorjehan Abdul; Narciso, Pasquale; Palombi, Leonardo; Renzi, Elsa; Zimba, Ines; Marazzi, Maria Cristina

    2008-05-15

    Maintaining treatment adherence among the growing number of patients receiving antiretroviral treatment in Africa is a dramatic challenge. The objective of our study was to explore the results of a computerized pill count method and to test the validity, sensitivity, and specificity of this method with respect to viral load measurement in an African setting. We performed a prospective, observational study involving patients who received first-line highly active antiretroviral therapy in Mozambique from 1 April 2005 through 31 March 2006. Enrolled patients had received treatment for at least 3 months before the study. For defining treatment adherence levels, pill counts were used, and the results were analyzed with viral load measurements at the end of the observation period. The study involved 531 participants. During the 12 months of observation, 137 patients left the program or discontinued first-line therapy. Of the remaining 394 patients, 284 (72.1%) had >95% treatment adherence; of those 284 patients, 274 (96.5%) had a final viral load 95% treatment adherence and the final viral load was closer than that between >90% treatment adherence and viral load. Treatment adherence >95% maximizes the results of the nonnucleoside reverse-transcriptase inhibitor-based regimen. The pill count method appears to be a reliable and economic tool for monitoring treatment adherence in resource-limited settings.

  16. [Study of the correlation between the plasma viral load and protective immunity induced by the equine infectious anemia attenuated vaccine and its parental virulent strain].

    Science.gov (United States)

    Cao, Xue-Zhi; Lin, Yue-Zhi; Li, Li; Jiang, Cheng-Gang; Zhao, Li-Ping; Lv, Xiao-Ling; Zhou, Jian-Hua

    2010-03-01

    The threshold hypothesis of attenuated lentiviral vaccine considers that the type of host response to infections of lentiviruses depends on the viral load. To evaluate the correlation between viral loads of the attenuated vaccine strain of equine infectious anemia virus (EIAV) and their effects to induce protective immunity, longitudinal plasma viral loads in groups of horses inoculated with either an attenuated EIAV vaccine strain (EIAV(DLV125)) or sub-lethal dose of an EIAV virulent strain (EIAV(LN40)) were compared. Similar levels of plasma viral loads ranging from 10(3)-10(5) copies/mL were detected from samples of these two groups of animals (P > 0.05) during 23 weeks post the inoculation. However, different responses to the challenge performed thereafter with lethal dose of the EIAV virulent strain were observed from the groups of horses inoculated with either EIAV(DLV125) or sub-lethal dose of EIAV(LN40). The protective efficiency was 67% (3 of 4 cases) and 0 (none of 2 cases), respectively. Our results implicate that the viral load of EIAV attenuated vaccine is not the primary factor, or at least not the solo primary factor, to determine the establishment of immune protection.

  17. HIV infection is influenced by dynamin at 3 independent points in the viral life cycle.

    Science.gov (United States)

    Aggarwal, Anupriya; Hitchen, Tina L; Ootes, Lars; McAllery, Samantha; Wong, Andrew; Nguyen, Khanh; McCluskey, Adam; Robinson, Phillip J; Turville, Stuart G

    2017-06-01

    CD4 T cells are important cellular targets for HIV-1, yet the primary site of HIV fusion remains unresolved. Candidate fusion sites are either the plasma membrane or from within endosomes. One area of investigation compounding the controversy of this field, is the role of the protein dynamin in the HIV life cycle. To understand the role of dynamin in primary CD4 T cells we combined dynamin inhibition with a series of complementary assays based on single particle tracking, HIV fusion, detection of HIV DNA products and active viral transcription. We identify 3 levels of dynamin influence on the HIV life cycle. Firstly, dynamin influences productive infection by preventing cell cycle progression. Secondly, dynamin influences endocytosis rates and increases the probability of endosomal fusion. Finally, we provide evidence in resting CD4 T cells that dynamin directly regulates the HIV fusion reaction at the plasma membrane. We confirm this latter observation using 2 divergent dynamin modulating compounds, one that enhances dynamin conformations associated with dynamin ring formation (ryngo-1-23) and the other that preferentially targets dynamin conformations that appear in helices (dyngo-4a). This in-depth understanding of dynamin's roles in HIV infection clarifies recent controversies and furthermore provides evidence for dynamin regulation specifically in the HIV fusion reaction. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A dynamic point-load test for quantifying rock dynamic strength parameters

    Science.gov (United States)

    Yu, Changyi; Yao, Wei; Xu, Ying; Xia, Kaiwen

    2017-11-01

    The point-load test (PLT) has been widely used in the field and in the laboratory to estimate the strength of rock materials. The PLT is easy and quick to perform and it is suitable for samples with irregular shapes and therefore has found wide applications. The measured point-load strength (PLS) is considered as a strength index and it has been correlated to the rock compressive strength. To address the engineering applications where the loading is dynamic, the PLT is extended to its dynamic version in this study. The dynamic loading is exerted to the rock specimen using a split Hopkinson pressure bar system. Two conical steel platens are attached to the incident bar and transmitted bar, respectively, to apply the point load to the disc specimen. To enable quasi-static analysis, the pulse shaper technique is utilized to achieve the dynamic force balance. The flexibility of the dynamic PLT method is demonstrated by the application to a well-studied granitic rock—Laurentian granite. The correlation between the dynamic PLS and the dynamic strength of the same rock is established.

  19. A stress and coping model of medication adherence and viral load in HIV-positive men and women on highly active antiretroviral therapy (HAART).

    Science.gov (United States)

    Weaver, Kathryn E; Llabre, María M; Durán, Ron E; Antoni, Michael H; Ironson, Gail; Penedo, Frank J; Schneiderman, Neil

    2005-07-01

    The authors tested a structural model that incorporated age, time since diagnosis, social support, coping, and negative mood as predictors of medication adherence and HIV viral load on 188 men and 134 women on highly active antiretroviral therapy (HAART). The authors used psychosocial latent factors formed from baseline measures to predict latent factors of adherence, as assessed by electronic monitoring and self-report, and viral load defined by indicators assessed over a 15-month period. Results from the model indicate that greater negative mood and lower social support are related to greater use of avoidance-oriented coping strategies. Use of these coping strategies by patients on HAART is related to poorer medication adherence and, subsequently, higher viral load. This model advances researchers' understanding of the contribution of psychosocial variables in predicting treatment adherence and disease progression in HIV-positive men and women.

  20. Factors associated with short-term changes in HIV viral load and CD4(+) cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Obel, Niels; Kirk, Ole

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...... collaboration study. METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations...... (95% CI) CD4(+) cell count change was -78.0 (-80.1 to -76.0) cell/μl per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4(+) cell count declined by an additional 37.6 cells/μl per year (P

  1. Melittin-loaded immunoliposomes against viral surface proteins, a new approach to antiviral therapy

    NARCIS (Netherlands)

    Falco Gracia, J.A.; Barrajon-Catalan, E.; Menendez-Gutierrez, M.P.; Coll, J.; Micol, V.; Estepa, A.

    2013-01-01

    In this study, melittin, a well-characterized pore-forming lytic amphiphilic peptide susceptible to be vehiculized in lipid membranes, has been utilized to study their antiviral properties. For this purpose, an assay based on melittin loaded-immunoliposomes previously described by our group was

  2. Research on stratified evolution of composite materials under four-point bending loading

    Science.gov (United States)

    Hao, M. J.; You, Q. J.; Zheng, J. C.; Yue, Z.; Xie, Z. P.

    2017-12-01

    In order to explore the effect of stratified evolution and delamination on the load capacity and service life of the composite materials under the four-point bending loading, the artificial tectonic defects of the different positions were set up. The four-point bending test was carried out, and the whole process was recorded by acoustic emission, and the damage degree of the composite layer was judged by the impact accumulation of the specimen - time-amplitude history chart, load-time-relative energy history chart, acoustic emission impact signal positioning map. The results show that the stratified defects near the surface of the specimen accelerate the process of material failure and expansion. The location of the delamination defects changes the bending performance of the composites to a great extent. The closer the stratification defects are to the surface of the specimen, the greater the damage, the worse the service capacity of the specimen.

  3. SEE Transient Response of Crane Interpoint Single Output Point of Load DC-DC Converters

    Science.gov (United States)

    Sanders, Anthony B.; Chen, Dakai; Kim, Hak S.; Phan, Anthony M.

    2011-01-01

    This study was undertaken to determine the single event effect and transient susceptibility of the Crane Interpoint Maximum Flexible Power (MFP) Single Output Point of Load DC/DC Converters for transient interruptions in the output signal and for destructive and non destructive events induced by exposing it to a heavy ion beam..

  4. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey.

    Science.gov (United States)

    Nguyen, Quyen Le Thi; Nguyen, Long Hoang; Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W B; Ho, Roger C M

    2017-01-01

    Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients' health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients' WTP for CD4 cell count and viral load testing. HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6-8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3-20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients.

  5. The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques

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    Rui-Rui Wang

    2015-01-01

    Full Text Available Ribosome inactivating proteins (RIPs inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV activity. Maize ribosome inactivating protein (RIP has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.

  6. Association between Vitamin D Status, Oxidative Stress Biomarkers and Viral Load in Human Immunodeficiency Virus Type 1 Infection.

    Science.gov (United States)

    Flauzino, Tamires; Simao, Andrea N C; de Almeida, Elaine R D; Morimoto, Helena K; Oliveira, Sayonara R; Alfieri, Daniela F; Ueda, Luiz T; Dichi, Isaias; Reiche, Edna M V

    2017-11-23

    The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values ≥30 ng/mL defined a vitamin D sufficient (VDS) status, and D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (pp=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (pp=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D ≥30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy.

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    Xavier Ferraretto

    Full Text Available It was demonstrated that combination antiretroviral therapy (cART reduces the HIV-1 viral load (VL in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129 or one sample (n = 48. All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5% from 17 patients (19.3%. This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129. Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

  8. High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

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    Grinsztejn Beatriz

    2010-12-01

    Full Text Available Abstract Background Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL and tegumentary leishmaniasis (ATL have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3. Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

  9. Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy.

    Science.gov (United States)

    Ferraretto, Xavier; Estellat, Candice; Damond, Florence; Longuet, Pascale; Epelboin, Sylvie; Demailly, Pauline; Yazbeck, Chadi; Llabador, Marie-Astrid; Pasquet, Blandine; Yazdanpanah, Yazdan; Matheron, Sophie; Patrat, Catherine

    2014-01-01

    It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

  10. Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Rybicki Ed

    2009-08-01

    Full Text Available Abstract Background Cervical cancer and infection with human immunodeficiency virus (HIV are both important public health problems in South Africa (SA. The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs, high-risk human papillomavirus (HR-HPV, HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2 test was used to detect HR-HPV. Relative light units (RLU were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene, the median HPV viral load was 181.1 RLU (HC2 positive samples only and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL. The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7 for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load, and 33.8 (95% CI 6.4 – 178.9 for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need

  11. Short-Term Power Load Point Prediction Based on the Sharp Degree and Chaotic RBF Neural Network

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    Dongxiao Niu

    2015-01-01

    Full Text Available In order to realize the predicting and positioning of short-term load inflection point, this paper made reference to related research in the field of computer image recognition. It got a load sharp degree sequence by the transformation of the original load sequence based on the algorithm of sharp degree. Then this paper designed a forecasting model based on the chaos theory and RBF neural network. It predicted the load sharp degree sequence based on the forecasting model to realize the positioning of short-term load inflection point. Finally, in the empirical example analysis, this paper predicted the daily load point of a region using the actual load data of the certain region to verify the effectiveness and applicability of this method. Prediction results showed that most of the test sample load points could be accurately predicted.

  12. Canine viral vaccines at a turning point--a personal perspective.

    Science.gov (United States)

    Carmichael, L E

    1999-01-01

    The most important canine viral infections are distemper and CPV-2. Problems of variable CD vaccine safety and efficacy persist, but CD vaccines have greatly reduced the prevalence of disease and cases in vaccinated dogs are now rare. Canine hepatitis (ICH, CAV-1 infection) also has been controlled well by vaccines for more than 35 years and it is now rare; the sporadic cases seen in the 1990s have usually occurred in unvaccinated dogs. CAV-2 vaccines should, therefore, continue to be given since they have proved to be safe and effective, and prevent hepatitis as well as adenoviral tracheobronchitis. Failure to vaccinate would likely result in increase in cases of ICH, a serious disease, but never as significant as distemper and CPV infection. "Are we vaccinating too often?" The question is complex, but the dominant opinion is "yes" (Smith, 1995). The question cannot be responded to unequivocally, however, since manufacturers employ different strains that vary in their immunizing capacity and, probably, duration of immunity. This question was frequent with distemper in the 1960s. At that time, many veterinarians tested batches of the vaccine they used by providing pre- and postvaccinal sera to competent diagnostic laboratories. That practice appeared to benefit veterinarians and dogs, as well as the quality of vaccines. Unfortunately, many owners and some veterinarians seem to hold the view that infectious diseases such as parvovirus infection can be controlled by frequent vaccination alone. The common practice of dog breeders of vaccinating their animals several times each year is senseless. Revaccination for distemper and parvovirus infection is suggested at 1 year of age, but recommendations regarding the frequency of most vaccinations given after that time are unclear. Since most distemper and CPV-2 vaccines probably provide immunity that endures several years, vaccination at 3- to 5-year intervals, after the first year, seems a reasonable practice until more

  13. Optimal timing of viral load monitoring during pregnancy to predict viraemia at delivery in HIV-infected women initiating ART in South Africa: a simulation study.

    Science.gov (United States)

    Lesosky, Maia; Glass, Tracy; Mukonda, Elton; Hsiao, Nei-Yuan; Abrams, Elaine J; Myer, Landon

    2017-11-01

    HIV viral load (VL) monitoring is a central tool to evaluate ART effectiveness and transmission risk. There is a global movement to expand VL monitoring following recent recommendations from the World Health Organization (WHO), but there has been little research into VL monitoring in pregnant women. We investigated one important question in this area: when and how frequently VL should be monitored in women initiating ART during pregnancy to predict VL at the time of delivery in a simulated South African population. We developed a mathematical model simulating VL from conception through delivery using VL data from the Maternal and Child Health - Antiretroviral Therapy (MCH-ART) cohort. VL was modelled based on three major compartments: pre-ART VL, viral decay immediately after ART initiation and viral maintenance (including viral suppression and viraemic episodes). Using this simulation, we examined the performance of various VL monitoring schema in predicting elevated VL at delivery. If WHO guidelines for non-pregnant adults were used, the majority of HIV-infected pregnant women (69%) would not receive a VL test during pregnancy. Most models that based VL monitoring in pregnancy on the time elapsed since ART initiation (regardless of gestation) performed poorly (sensitivity ART) appeared to perform better overall (sensitivity >60%). Across all permutations, inclusion of pre-ART VL values had a negligible impact on predictive performance (improving test sensitivity and specificity Performance of VL monitoring in predicting VL at delivery generally improved at later gestations, with the best performing option a single VL measure at 36 weeks' gestation. Development and evaluation of a novel simulation model suggests that strategies to measure VL relative to gestational age may be more useful than strategies relative to duration on ART, in women initiating ART during pregnancy, supporting better integration of maternal and HIV health services. Testing turnaround times

  14. Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses

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    Chuchottaworn Charoen

    2010-04-01

    Full Text Available Abstract Background Nasopharyngeal aspirate (NPA, nasal swab (NS, and throat swab (TS are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number. Results Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus, NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed. Conclusion Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS.

  15. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

    Science.gov (United States)

    Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

    2015-02-14

    To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real

  16. Patient Use of Electronic Prescription Refill and Secure Messaging and Its Association With Undetectable HIV Viral Load: A Retrospective Cohort Study.

    Science.gov (United States)

    McInnes, D Keith; Shimada, Stephanie L; Midboe, Amanda M; Nazi, Kim M; Zhao, Shibei; Wu, Justina; Garvey, Casey M; Houston, Thomas K

    2017-02-15

    Electronic personal health records (PHRs) can support patient self-management of chronic conditions. Managing human immunodeficiency virus (HIV) viral load, through taking antiretroviral therapy (ART) is crucial to long term survival of persons with HIV. Many persons with HIV have difficulty adhering to their ART over long periods of time. PHRs contribute to chronic disease self-care and may help persons with HIV remain adherent to ART. Proportionally veterans with HIV are among the most active users of the US Department of Veterans Affairs (VA) PHR, called My HealtheVet. Little is known about whether the use of the PHR is associated with improved HIV outcomes in this population. The objective of this study was to investigate whether there are associations between the use of PHR tools (electronic prescription refill and secure messaging [SM] with providers) and HIV viral load in US veterans. We conducted a retrospective cohort study using data from the VA's electronic health record (EHR) and the PHR. We identified veterans in VA care from 2009-2012 who had HIV and who used the PHR. We examined which ones had achieved the positive outcome of suppressed HIV viral load, and whether achievement of this outcome was associated with electronic prescription refill or SM. From 18,913 veterans with HIV, there were 3374 who both had a detectable viral load in 2009 and who had had a follow-up viral load test in 2012. To assess relationships between electronic prescription refill and viral control, and SM and viral control, we fit a series of multivariable generalized estimating equation models, accounting for clustering in VA facilities. We adjusted for patient demographic and clinical characteristics associated with portal use. In the initial models, the predictor variables were included in dichotomous format. Subsequently, to evaluate a potential dose-effect, the predictor variables were included as ordinal variables. Among our sample of 3374 veterans with HIV who received

  17. The quantification of hepatitis C viral load using an In-House Real-Time PCR assay in HCV infected patients in Khorramabad city

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    kiyana Shahzamani

    2016-05-01

    Full Text Available Background : Molecular diagnostic methods are among major tools in management of hepatitis C virus (HCV in infected patients. Many studies have shown that viral load is associated with stage of infection and response to treatment. Therefore, the evaluation and quantification of viral load is very important. The goal of this study is implementation of inexpensive, yet accurate method for quantitative assessment of viral load in plasma samples of infected patients. Materials and Methods: After development and validation of the assay, quantification of HCV RNA on 200 chronic patients the start of therapy was performed using an In-House Real-time PCR assay. Measuring the concentration of viral RNA was performed using an external standard curve. It should be noted that the validation and standardization of all procedures in this study were performed using RNA standard panel. The results of this method were compared with results obtained from Artus commercial kit. Results: Detection limit of the assay was 50 IU/ml. The mean viral load measured on a logarithmic scale (5/81± 0/22, p<0/05. Parallel analysis of samples with commercial kit showed that there is a good correlation between these two methods (R2 = 0.988 p< 0.05. Conclusion: Viral load detection of HCV was reported for the first time in Khorramabad city.  According to the results, this method has a good sensitivity and specificity for HCV quantification in large-scale. It can be a good replacement for commercial kits especially for clinical evaluation of therapy.

  18. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening.

    Science.gov (United States)

    Kawada, Jun-ichi; Torii, Yuka; Kawano, Yoshihiko; Suzuki, Michio; Kamiya, Yasuko; Kotani, Tomomi; Kikkawa, Fumitaka; Kimura, Hiroshi; Ito, Yoshinori

    2015-04-01

    Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children.

    Science.gov (United States)

    Bingler, M A; Feingold, B; Miller, S A; Quivers, E; Michaels, M G; Green, M; Wadowsky, R M; Rowe, D T; Webber, S A

    2008-02-01

    Increased use of serial EBV-PCR monitoring after pediatric transplantation has led to the identification of asymptomatic patients who carry very high viral loads over prolonged periods. The significance of this high-load state is unknown. We speculated that this state may identify patients at high risk for development of late PTLD/lymphoma. We reviewed data on 71 pediatric heart recipients who had serial viral load monitoring since 1997. Chronic high-load state was defined as the presence of >16,000 genome copies/mL whole blood on > or =50% of samples over at least 6 months. Among 20 high-load carriers (eight following prior PTLD, seven with prior symptomatic EBV infection, five without previous EBV disease), 9 (45%) developed late-onset PTLD 2.5-8.4 years posttransplant (including with four Burkitt's lymphoma). Among 51 controls with low (n = 39) or absent (n = 12) loads, only 2 (4%; p < 0.001 absent/low vs. high load) developed late PTLD/lymphoma. By multivariable analysis, high-load carrier state (OR = 12.4, 95% CI 2.1-74.4) and prior history of PTLD (OR = 10.7, 95% CI 1.9-60.6) independently predicted late PTLD. A chronic high EBV-load state is not benign and is a predictor of de novo or recurrent PTLD.

  20. Evaluation of the maximum loadability point of power systems considering the effect of static load models

    International Nuclear Information System (INIS)

    Amjady, Nima; Velayati, Mohammad Hossein

    2009-01-01

    Power system stability is an important problem for power system operation. Determination of different stability margins can result in the optimum utilization of power system with minimum risk. Voltage stability is an important subset of power system stability. To correctly analyze the voltage stability of a power system, suitable dynamic models are usually required. However, static analysis tools can give us useful information about long term voltage stability. Especially, maximum loadability point (MLP) of a power system can be effectively estimated by modal analysis of load flow Jacobians. MLP is one of the important boundaries of voltage stability feasible region that loading beyond which is of little practical meaning. In this paper, MLP boundary of power system is analyzed by means of static analysis tools and its differences with the other boundaries of voltage stability, like saddle node bifurcation, are discussed. Effect of reactive power limits of generators and different static load models on the MLP border is also evaluated.

  1. Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impacts viral set point

    Science.gov (United States)

    Ndhlovu, Zaza; Kamya, Philomena; Mewalal, Nikoshia; Kløverpris, Henrik N.; Nkosi, Thandeka; Pretorius, Karyn; Laher, Faatima; Ogunshola, Funsho; Chopera, Denis; Shekhar, Karthik; Ghebremichael, Musie; Ismail, Nasreen; Moodley, Amber; Malik, Amna; Leslie, Alasdair; Goulder, Philip J.R; Buus, Søren; Chakraborty, Arup; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.

    2015-01-01

    Summary CD8+ T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified twelve hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8+ T cell response, with limited bystander activation of non-HIV memory CD8+ T cells. HIV-specific CD8+ T cells secreted little interferon-γ, underwent rapid apoptosis and failed to upregulate the interleukin 7 receptor, known to be important for T cell survival. The rapidity to peak CD8+ T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8+ T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. PMID:26362266

  2. Physical state and viral load as predictive biomarkersfor persistence and progression of HPV16-positive cervical lesions: results from a population based long-term prospective cohort study.

    Science.gov (United States)

    Manawapat, Anna; Stubenrauch, Frank; Russ, Rainer; Munk, Christian; Kjaer, Susanne Kruger; Iftner, Thomas

    2012-01-01

    Persistent infection with a high risk (hr) human papillomavirus (HPV) has been established as the main cause of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN3). Because most infections are transient, testing for hrHPV lacks specificity and has a low positive predictive value. It has been suggested that additional parameters like viral load and physical status of the viral genome could improve the effectiveness of HPV-based screening. We investigated the association between HPV16 viral load and physical state with viral persistence or risk of incident CIN3 or worse in a population-based prospective cohort study comprising 8656 women (20-29 years). All participants had two gynecological examinations two years apart and were followed through the nationwide Danish Pathology Data Bank (median follow-up: 12.9 yrs). Seventynine cervical swabs from women with a persistent HPV16 infection were available for analysis. For comparison we selected a random age-matched sample of transiently HPV16 infected women (N=91). Persistently infected women with incident CIN3 or cancer (CIN3+; N=31) were compared to women with normal cytology during follow up (non-progressors; N=39). Quantitative real-time PCR for HPV16E6, E2 and IFNb1 was done to determine the HPV16 viral load and the E2/E6 ratio was used as a surrogate marker for integration. Women with normal cytology who became persistently HPV16 infected had a significantly lower HPV16 load at baseline than women who cleared the infection (median 4.72 copies/cell versus median 20.0 copies/cell, respectively; p=0.0003). There was no difference in viral load at enrollment between women who progressed to CIN3+ and women who stayed cytologically normal (p=0.85). At the second examination viral load tended to be higher in women who progressed, but the difference was not statistically significant (p=0.39). The E2/E6 ratio was shown to be lower in the persistently infected group (pload and integration of the viral

  3. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women

    NARCIS (Netherlands)

    Ondoa, Pascale; Gautam, Raju; Rusine, John; Lutter, Rene; Jurriaans, Suzanne; Kootstra, Neeltje; Karita, Etienne; van de Wijgert, Janneke

    2015-01-01

    Genital viral load (GVL) is the main determinant of sexual transmission of human immune-deficiency virus (HIV). The effect of antiretroviral therapy (ART) on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL,

  4. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 yea...

  5. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial

    NARCIS (Netherlands)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B.; Kuiken, Sjoerd D.; Weijer, Sebastiaan; van Nieuwkerk, Carin M. J.; Zaaijer, Hans L.; Molenkamp, Richard; Takkenberg, R. Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W.

    2017-01-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen

  6. A measurement model of medication adherence to highly active antiretroviral therapy and its relation to viral load in HIV-positive adults.

    Science.gov (United States)

    Llabre, Maria M; Weaver, Kathryn E; Durán, Ron E; Antoni, Michael H; McPherson-Baker, Shvawn; Schneiderman, Neil

    2006-10-01

    This study compared a multiple method measurement model of highly active antiretroviral therapy (HAART) adherence with single-method models to determine optimal validity in predicting HIV viral load. Repeated measures of antiretroviral adherence were collected over a 15-month period using three different measurement methods: a self-report questionnaire, an adherence interview item, and electronic medication monitoring. The participants included HIV-positive men and women (n = 323) who were currently prescribed HAART. Single-factor models composed of multiple measurements over time were developed for each adherence method and HIV viral load. The three adherence methods were then combined in a second order factor measurement model. Structural equation modeling was used to test the models. Mean adherence, defined as percent of doses taken, was 92%, 90%, and 57% by self-report, interview, and electronic monitoring, respectively. Reliability of individual measurements of adherence was low. Four or seven assessments were needed to attain acceptable stability, depending on the method. The second-order factor model of adherence fit the data and explained 45% of the variability in HIV viral load. Models including only one method of assessing adherence explained between 20% and 24% of the variability. Models that included both self-report and electronic monitoring optimized predictive validity. Using at least two different methods of adherence measurement, each assessed at multiple times is recommended to derive reliable and valid measurement of medication adherence, which is predictive of biological outcomes such as HIV viral load.

  7. Frequency of FOXP3+ Regulatory T-cells in the Blood of Chronic Hepatitis C Patients with Immune Mediated Skin Manifestations; Relationship to Hepatic Condition and Viral Load.

    Science.gov (United States)

    Farid, Carmen; Sheikh, Wafaa El; Swelem, Rania; El-Ghitany, Engy

    2016-12-01

    Chronic hepatitis C (CHC) infection causes a wide range of immune mediated hepatic and extrahepatic manifestations. Cutaneous manifestations constitute a major portion of the latter group. Host immune response to the virus - particularly regulatory T lymphocytes - is important in determining the outcome of the infection and the possibility of extrahepatic manifestations. The present study aims to investigate the relationship between immune-mediated cutaneous manifestations of CHC infection and the frequency of CD4+CD25 high FOXP3+ T regulatory lymphocytes. We also investigated the relationships to viral load and hepatic conditions. A total of 58 CHC patients (30 had cutaneous manifestations and 28 did not) and 30 healthy HCV free subjects were enrolled in this study. The frequency of CD4+CD25 high FOXP3+ Treg cells was measured in the peripheral blood of all participants. Additionally, serum ALT, RNA viral load, and hepatic ultrasonographic studies were performed for all patients. Skin manifestations were dominated by small vessel vasculitis and to a lesser extent lichen planus. Treg cell frequency was significantly lower in CHC patients with skin manifestations compared to those without. Chronic hepatic insult was significantly more common among patients with skin manifestations, although serum ALT levels were significantly lower in this group. Treg frequencies did not correlate to either ALT level or viral load. HCV-associated skin lesions are associated with low frequency of Treg cells. They are not related to liver enzymes or viral load; however, they are associated with a more advanced gross liver insult.

  8. Comparative study of cytomegalovirus antibody and viral load in schizophrenia and bipolar patients

    Directory of Open Access Journals (Sweden)

    Farid Suleimani Mohammadi

    2017-02-01

    Full Text Available Background: Schizophrenia (SC and bipolar disorder (BD are two chronic psychiatric illnesses with worldwide distribution. People could be involved at any age, particularly in early adolescence. Main symptoms of SC are non- affective symptoms such as auditory hallucination and illogical thinking. In contrast, BD represents affective symptoms such as depression and mania. Although the main cause of these mood disorders has been remained elusive, there are some potential contributing factors that could be considered in the pathogenesis of mentioned illnesses including, genetic and environmental factors. Cytomegalovirus (CMV is one of the probable contributing factors in SC and BD. CMV is a prototype of herpesviridae family which may infect different cell types such as endothelial and differentiated hematopoietic cells. CMV infections in immunocompromised patients as well as congenitally infected children represent CNS complication such as microcephaly and hearing loss. This virus has capability to impair the limbic structures in brain. Methods: This descriptive study was designed to evaluate the role of CMV in these illnesses. We investigated the level of serum IgG antibody and the presence of CMV DNA in serum and peripheral blood mononuclear cells (PBMCs samples of 46 SC and BD patients admitted to Iran Psychiatry Hospital Tehran, Iran from 2014 to 2015 as well as 46 healthy control groups at Tehran University of Medical Sciences.  First, the level of CMV IgG antibody was evaluated in serum samples, by enzyme-linked immunosorbent assay (ELISA. Then, DNA extraction conducted by using the high pure viral nucleic acid kit (Roche, Germany. Serologically positive sera along with PBMC samples were tested by Real-time PCR, to investigate the presence of CMV DNA. Results: Results indicated higher levels of CMV IgG antibody in psychiatric patients, compared with a healthy control group. Afterward, we did not observe the presence of CMV DNA in either case

  9. High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa.

    Science.gov (United States)

    Etta, Elizabeth M; Mavhandu, Lufuno; Manhaeve, Cecile; McGonigle, Keanan; Jackson, Patrick; Rekosh, David; Hammarskjold, Marie-Louise; Bessong, Pascal O; Tebit, Denis M

    2017-07-27

    Combination antiretroviral therapy (cART) has significantly reduced HIV morbidity and mortality in both developed and developing countries. However, the sustainability of cART may be compromised by the emergence of viral drug resistance mutations (DRM) and the cellular persistence of proviruses carrying these DRM. This is potentially a more serious problem in resource limited settings. DRM were evaluated in individuals with unsuppressed viral loads after first or multiple lines of cART at two sites in rural Limpopo, South Africa. Seventy-two patients with viral loads of >1000 copies/ml were recruited between March 2014 and December 2015. Complete protease (PR) and partial Reverse Transcriptase (RT) sequences were amplified from both plasma RNA and paired proviral DNA from 35 of these subjects. Amplicons were directly sequenced to determine subtype and DRM using the Stanford HIV Drug Resistance Interpretation algorithm. Among the 72 samples, 69 could be PCR amplified from RNA and 35 from both RNA and DNA. Sixty-five (94.2%) viruses were subtype C, while one was subtype B (1.4%), one recombinant K/C, one recombinant C/B and one unclassified. Fifty-eight (84%) sequences carried at least one DRM, while 11 (15.9%) displayed no DRM. DRM prevalence according to drug class was: NRTI 60.8% NNRTI 65.2%, and PI 5.8%. The most common DRMs were; M184V (51.7%), K103N (50%), V106M (20.6%), D67N (13.3%), K65R (12%). The frequency of the DRM tracked well with the frequency of use of medications to which the mutations were predicted to confer resistance. Interestingly, a significant number of subjects showed predicted resistance to the newer NNRTIs, etravirine (33%) and rilpivirine (42%), both of which are not yet available in this setting. The proportion of DRM in RNA and DNA were mostly similar with the exception of the thymidine analogue mutations (TAMs) D67N, K70R, K219QE; and K103N which were slightly more prevalent in DNA than RNA. Subjects who had received cART for at least

  10. Large deflection analysis of cantilever beam under end point and distributed load

    DEFF Research Database (Denmark)

    Kimiaeifar, Amin; Tolou, N; Barari, Amin

    2014-01-01

    distributed loads. Direct nonlinear solution by use of homotopy analysis method was implemented to drive the semi-exact solution of trajectory position of any point along the beam length. For the purpose of comparison, the deflections were calculated and compared to those of finite element method which...... requires numerical solution of simultaneous equations which is a significant drawback for optimization or reliability analysis. This paper is motivated to overcome these shortcomings by presenting an analytical solution for the large deflection analysis of a cantilever beam under free end point and uniform...

  11. TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

    Science.gov (United States)

    Petta, S; Di Marco, V; Di Stefano, R; Cabibi, D; Cammà, C; Marchesini, G; Craxì, A

    2011-07-01

    The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load. © 2011 Blackwell Publishing Ltd.

  12. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

    Science.gov (United States)

    Soulie, Cathia; Grudé, Maxime; Descamps, Diane; Amiel, Corinne; Morand-Joubert, Laurence; Raymond, Stéphanie; Pallier, Coralie; Bellecave, Pantxika; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Montes, Brigitte; Barin, Francis; Ferré, Virginie; Jeulin, Hélène; Alloui, Chakib; Yerly, Sabine; Signori-Schmuck, Anne; Guigon, Aurélie; Fafi-Kremer, Samira; Haïm-Boukobza, Stéphanie; Mirand, Audrey; Maillard, Anne; Vallet, Sophie; Roussel, Catherine; Assoumou, Lambert; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Geneviève

    2017-08-01

    HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Chronic hepatitis C virus infection and subsequent HIV viral load among women with HIV initiating antiretroviral therapy.

    Science.gov (United States)

    Willis, Sarah J; Cole, Stephen R; Westreich, Daniel; Edmonds, Andrew; Hurt, Christopher B; Albrecht, Svenja; Anastos, Kathryn; Augenbraun, Michael; Fischl, Margaret; French, Audrey L; Kalapila, Aley G; Karim, Roksana; Peters, Marion G; Plankey, Michael; Seaberg, Eric C; Tien, Phyllis C; Adimora, Adaora A

    2018-03-13

    One in four persons living with HIV is coinfected with hepatitis C virus (HCV). Biological and behavioral mechanisms may increase HIV viral load among coinfected persons. Therefore, we estimated the longitudinal effect of chronic HCV on HIV suppression after ART initiation among women with HIV (WWH). HIV RNA was measured every 6 months among 441 WWH in the Women's Interagency HIV Study who initiated ART from 2000 to 2015. Log-binomial regression models were used to compare the proportion of study visits with detectable HIV RNA between women with and without chronic HCV. Robust sandwich variance estimators accounted for within-person correlation induced by repeated HIV RNA measurements during follow-up. We controlled for confounding and selection bias (because of loss to follow-up and death) using inverse probability-of-exposure-and-censoring weights. One hundred and fourteen women (25%) had chronic HCV before ART initiation. Overall, the proportion of visits with detectable HIV RNA was similar among women with and without chronic HCV [relative risk (RR) 1.19 (95% CI 0.72, 1.95)]. Six months after ART initiation, the proportion of visits with detectable HIV RNA among women with chronic HCV was 1.88 (95% CI 1.41-2.51) times that among women without HCV, at 2 years, the ratio was 1.60 (95% CI 1.17-2.19), and by 6 years there was no difference (1.03; 95% CI 0.60-1.79). Chronic HCV may negatively impact early HIV viral response to ART. These findings reaffirm the need to test persons with HIV for HCV infection, and increase engagement in HIV care and access to HCV treatment among persons with HIV/HCV coinfection.

  14. Continuous 'Passive' Registration of Non-Point Contaminant Loads Via Agricultural Subsurface Drain Tubes

    Science.gov (United States)

    Rozemeijer, J.; Jansen, S.; de Jonge, H.; Lindblad Vendelboe, A.

    2014-12-01

    Considering their crucial role in water and solute transport, enhanced monitoring and modeling of agricultural subsurface tube drain systems is important for adequate water quality management. For example, previous work in lowland agricultural catchments has shown that subsurface tube drain effluent contributed up to 80% of the annual discharge and 90-92% of the annual NO3 loads from agricultural fields towards the surface water. However, existing monitoring techniques for flow and contaminant loads from tube drains are expensive and labor-intensive. Therefore, despite the unambiguous relevance of this transport route, tube drain monitoring data are scarce. The presented study aimed developing a cheap, simple, and robust method to monitor loads from tube drains. We are now ready to introduce the Flowcap that can be attached to the outlet of tube drains and is capable of registering total flow, contaminant loads, and flow-averaged concentrations. The Flowcap builds on the existing SorbiCells, a modern passive sampling technique that measures average concentrations over longer periods of time (days to months) for various substances. By mounting SorbiCells in our Flowcap, a flow-proportional part of the drain effluent is sampled from the main stream. Laboratory testing yielded good linear relations (R-squared of 0.98) between drainage flow rates and sampling rates. The Flowcap was tested in practice for measuring NO3 loads from two agricultural fields and one glasshouse in the Netherlands. The Flowcap registers contaminant loads from tube drains without any need for housing, electricity, or maintenance. This enables large-scale monitoring of non-point contaminant loads via tube drains, which would facilitate the improvement of contaminant transport models and would yield valuable information for the selection and evaluation of mitigation options to improve water quality.

  15. Chronic hepatitis C virus infection and increases in viral load in a prospective cohort of young, HIV-uninfected injection drug users.

    Science.gov (United States)

    Boodram, Basmattee; Hershow, Ronald C; Cotler, Scott J; Ouellet, Lawrence J

    2011-12-15

    Chronic hepatitis C (HCV) infection, defined as persistent RNA (viral load) for at least 6 months, accounts for up to 50% of all cirrhosis, end-stage liver disease and liver cancer cases. Moreover, elevated HCV viral load is consistently associated with high infectivity and poor therapy response. This study aims to identify modifiable behavioral correlates both chronic HCV infection and increases in viral load over time among injection drug users (IDUs). Cross-sectional and longitudinal analyses were performed using self-interview and serological data from a prospective cohort study (2002-2006) among young (age 18-35), HIV-negative, HCV therapy-naïve IDUs (n=113) from metropolitan Chicago, Illinois, USA. After adjustment for age, gender and race/ethnicity, using drugs measured or mixed in someone else's syringe (odds ratio=2.7, 95% confidence interval: 1.1, 6.7) was associated with chronic (n=75, 66%) versus resolved (n=38, 34%) HCV infection status. Among chronically-infected IDUs, injecting with a new, sterile syringe infrequently (<1/2 half the time when injecting) compared to frequently (1/2 the time or more when injecting) was associated with increases in viral load over time after adjusting for age, gender, race/ethnicity and time effects. Reductions in risky injection-related practices among young IDUs may ameliorate both the burden of chronic HCV infection-related liver disease and elevated viral load-related poor treatment response. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+T lymphocyte count and detection of EBV, CMV and HSV

    OpenAIRE

    Grando,Liliane Janete; Machado,Denise Cantarelli; Spitzer,Silvia; Nachman,Sharon; Ferguson,Fred; Berentsen,Bárbara; Yurgel,Liliane Soares

    2005-01-01

    Viral coinfection in the oral cavity associated to HIV infection was evaluated in 180 children from birth to 13 years of age of both sexes. The oral examinations were performed at the Pediatric AIDS Outpatient Clinic, São Lucas Hospital and Clinic Hospital, both in Porto Alegre, Brazil and at the School of Dental Medicine, University Hospital Center, State University of New York at Stony Brook, USA. The aim of this study was to identify the presence of viral infections in the oral cavity. PCR...

  17. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

    Directory of Open Access Journals (Sweden)

    Papa Saliou Mbaye

    Full Text Available BACKGROUND AND AIMS: Despite the high prevalence of chronic hepatitis B (CHB in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM and two biochemical scores (FibroTest®, Fibrometer® to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10 IU/mL and normal alanine aminotransferase (ALT values. METHODS: LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB. Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. RESULTS: 225 patients were evaluated (84% male and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT, and Fibrometer® (FM using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. CONCLUSION: In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.

  18. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

    Energy Technology Data Exchange (ETDEWEB)

    Hood, Iris V.; Berger, James M.

    2016-05-31

    Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of theStaphylococcus aureusreplicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.

  19. Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients.

    Science.gov (United States)

    Jones, D C; Peacock, S; Hughes, D; Traherne, J A; Allen, R L; Barnardo, M C N M; Friend, P; Taylor, C J; Fuggle, S; Trowsdale, J; Young, N T

    2014-12-01

    Killer cell immunoglobulin-like receptors (KIR) are highly polymorphic members of the immunoglobulin superfamily, which influence the response of natural killer cells and some T-lymphocyte subsets. Analysis of a cohort of previously human cytomegalovirus (HCMV)-negative patients, who developed primary HCMV infection following HCMV-positive renal transplant (n=76), revealed an increase in the frequency of KIR genes located on the telomeric region of B haplotypes (Tel B). The presence of Tel B in combination with the KIR ligand HLA-C2 was significantly more frequent in this subgroup. These genetic factors were associated with resistance to HCMV infection in a second cohort (n=65), where the Tel B genes KIR2DL5, -2DS1, 2DS5 and -3DS1 were all significantly associated with high viral loads. Furthermore, the KIR haplotype Tel A when in combination with the KIR ligand HLA-C1 was significantly protective against the development of severe infection. Our results suggest that KIR are a significant factor in the control of primary HCMV infection, and that determination of KIR gene repertoire may help in detection of renal transplant patients who were most at risk.

  20. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Directory of Open Access Journals (Sweden)

    Juan Pablo Rodriguez-Auad

    2015-01-01

    Full Text Available Monitoring antiretroviral therapy using measurements of viral load (VL and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6% of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

  1. Evaluation of the cobas® GT hepatitis C virus genotyping assay in G1-6 viruses including low viral loads and LiPA failures.

    Science.gov (United States)

    Némoz, Benjamin; Roger, Léa; Leroy, Vincent; Poveda, Jean-Dominique; Morand, Patrice; Larrat, Sylvie

    2018-01-01

    Direct-acting antiviral (DAA) drug performances depend on the viral genotype. So international recommendations give typing of the virus a prerequisite for treatment choice and patient management. Commercially available HCV genotyping kits are scarce and this analysis is often in-house using tedious PCRs and Sanger sequencing, leading to a lack of standardization. A newly commercialized HCV genotyping assay based on real-time PCR has been developed by Roche Diagnostics (Mannheim, Germany). We compared this new assay with our in-house PCRs -sequencing technique on 101 regular samples and 81 LiPA failures or low viral load samples. No genotype or 1a/1b subtype mismatch was observed. Two samples were misidentified at the subtype level without clinical impact. Three genotype 1b and two genotype 1a samples with low viral load could not be subtyped. Nevertheless, 13 (13%) samples from the regular panel and 35 (43%) from the more difficult-to-type panels failed to give results on first pass with the Roche kit. Failures were mostly associated with genotype 3 subtype a, with genotype 4 subtype non-a, or with viral loads <200 IU/mL (p = 0.0061). The workflow allowed a non-specialized technician to obtain results in less than 4 hours whereas 2 to 3 days and experienced staff were required with the in-house assay. In conclusion, the Roche cobas® HCV GT kit is easy and rapid to use and provides reliable results. The high rate of uninterpretable results particularly for low viral load samples and less frequent genotypes, and the absence of subtyping for non-genotype 1 could require sending complex samples to a specialized laboratory.

  2. Differences in circulating MMP-9 levels with regard to viral load and AST:ALT ratio between chronic hepatitis B and C patients.

    Science.gov (United States)

    Helaly, G F

    2011-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the two major causes of chronic liver inflammation, fibrosis and cirrhosis. They have the ability to cause persistent infection in susceptible hosts and severely damage liver function. Matrix metalloproteinase-9 (MMP-9) is one of the gelatinases that may be important in liver fibrosis. This study aims to evaluate whether or not MMP-9 in relation to viral load is involved in the development of liver dysfunction in HBV and HCV Blood samples from 20 patients chronically infected with HBV and 30 with HCV, along with 15 healthy individuals as controls, were investigated. Viral load was assessed by real-time polymerase chain reaction (PCR). Serum MMP-9 levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Alanine transaminase and aspartate aminotransferase (ALT and AST) activities were measured spectrophotometrically. Levels of MMP-9 were significantly higher in HCV than in HBV patients (P < 0.01), and positively correlated with HBV viral load (r = 0.842, P < 0.01) and AST:ALT ratio (r = 0.614, P < 0.05). Conversely, MMP-9 levels did not correlate with HCV viral load but did correlate with AST:ALT ratio (r = 0.652, P < 0.01). Therefore, MMP-9 levels could reflect progressive liver damage in HBV and HCV infection. However, a distinction between the pathological mechanism of HCV and HBV is suggested, as HCV probably promotes hepatocyte damage and fibrosis through mechanisms other than replication. Continuous expression of the HBV genome through replication and secretion of viral antigens may contribute to the transcriptional regulation of MMP-9, thus promoting liver damage and fibrosis.

  3. Simplified Probabilistic Analysis of Settlement of Cyclically Loaded Soil Stratum by Point Estimate Method

    Science.gov (United States)

    Przewłócki, Jarosław; Górski, Jarosław; Świdziński, Waldemar

    2016-12-01

    The paper deals with the probabilistic analysis of the settlement of a non-cohesive soil layer subjected to cyclic loading. Originally, the settlement assessment is based on a deterministic compaction model, which requires integration of a set of differential equations. However, with the use of the Bessel functions, the settlement of a soil stratum can be calculated by a simplified algorithm. The compaction model parameters were determined for soil samples taken from subsoil near the Izmit Bay, Turkey. The computations were performed for various sets of random variables. The point estimate method was applied, and the results were verified by the Monte Carlo method. The outcome leads to a conclusion that can be useful in the prediction of soil settlement under seismic loading.

  4. Planetary Load Sharing in Three-Point- Mounted Wind Turbine Gearboxes: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yi [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Keller, Jonathan A [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-15

    Wind turbine gearboxes do not achieve their expected design life. The cost of gearbox replacements and rebuilds and the downtime associated with these failures increase the cost of wind energy. In 2007, the U.S. Department of Energy established the National Renewable Energy Laboratory (NREL) Gearbox Reliability Collaborative (GRC). Its goals are to understand the root causes of premature gearbox failures and improve their reliability. To date, the GRC has focused on a 750-kW drivetrain with a three-stage, three-point-mounted gearbox. A nonproprietary version of the gearbox containing CRBs with C3 clearances in the planetary stage was customized. Two of these gearboxes, GB1 and GB2, were manufactured and then tested in the National Wind Technology Center's 2.5-MW dynamometer and in the field. Major GRC findings include the detrimental effect of rotor moments on planetary load sharing and predicted fatigue, and the risk of bearing sliding in low-torque conditions for three-point configuration drivetrains. Based on the knowledge gained from testing and analysis of the original design, the GRC gearbox was redesigned to improve its load-sharing characteristics and predicted fatigue. This new gearbox is named GB3. As shown in Figure 1, its key improvement is the incorporation of preloaded TRBs that support the planet carrier and planets. Roller loads can be optimized and bearing life maximized with a small preload [4]. These preloaded bearings, along with interference-fitted planet pins, improve alignments and load-sharing characteristics. A semi-integrated planet bearing design also increases capacity and eliminates outer race fretting. Romax Technology, with Powertrain Engineers and the Timken Company (Timken), completed the redesign. Timken manufactured and instrumented the planet gears and bearings. Brad Foote Gearing manufactured the other gearing and assembled the gearbox.

  5. Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer.

    Science.gov (United States)

    Depuydt, Christophe E; Thys, Sofie; Beert, Johan; Jonckheere, Jef; Salembier, Geert; Bogers, Johannes J

    2016-11-01

    Persistent high-risk human papillomavirus (HPV) infection is strongly associated with development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type-specific viral-load measurements predict the natural history of the infection. In infections with multiple HPV-types, the individual type-specific viral-load profile could distinguish progressing HPV-infections from regressing infections. A case-cohort natural history study was established using samples from untreated women with multiple HPV-infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real-time qPCR-assay (18 HPV-types). Using serial type-specific viral-load measurements (≥3) we calculated HPV-specific slopes and coefficient of determination (R(2) ) by linear regression. For each woman slopes and R(2) were used to calculate which HPV-induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV-types, each single HPV-type generated similar increasing (0.27copies/cell/day) and decreasing (-0.27copies/cell/day) viral-load slopes. In CIN3+, at least one of the HPV-types had a clonal progressive course (R(2)  ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type-specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion-producing infections the RNA-staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly-formed virions. RNA-hybridization patterns matched the calculated ongoing processes measured by R(2) and slope in serial type-specific viral-load measurements preceding the biopsy. In women with multiple HPV-types, serial type-specific viral-load measurements predict the natural history of the

  6. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey.

    Directory of Open Access Journals (Sweden)

    Quyen Le Thi Nguyen

    Full Text Available Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes.A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART in Hanoi and Nam Dinh. Patients' health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients' WTP for CD4 cell count and viral load testing.HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI and had the overall the poorest quality of life. Most patients (90.9% were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6-8.8 US$ per test. Most patients (87.3% were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3-20.9 US$ per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP.These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients.

  7. Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses.

    Science.gov (United States)

    Ederveen, Thomas H A; Ferwerda, Gerben; Ahout, Inge M; Vissers, Marloes; de Groot, Ronald; Boekhorst, Jos; Timmerman, Harro M; Huynen, Martijn A; van Hijum, Sacha A F T; de Jonge, Marien I

    2018-01-11

    While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA. Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels. The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.

  8. Comparison of point-source pollutant loadings to soil and groundwater for 72 chemical substances.

    Science.gov (United States)

    Yu, Soonyoung; Hwang, Sang-Il; Yun, Seong-Taek; Chae, Gitak; Lee, Dongsu; Kim, Ki-Eun

    2017-11-01

    Fate and transport of 72 chemicals in soil and groundwater were assessed by using a multiphase compositional model (CompFlow Bio) because some of the chemicals are non-aqueous phase liquids or solids in the original form. One metric ton of chemicals were assumed to leak in a stylized facility. Scenarios of both surface spills and subsurface leaks were considered. Simulation results showed that the fate and transport of chemicals above the water table affected the fate and transport of chemicals below the water table, and vice versa. Surface spill scenarios caused much less concentrations than subsurface leak scenarios because leaching amounts into the subsurface environment were small (at most 6% of the 1 t spill for methylamine). Then, simulation results were applied to assess point-source pollutant loadings to soil and groundwater above and below the water table, respectively, by multiplying concentrations, impact areas, and durations. These three components correspond to the intensity of contamination, mobility, and persistency in the assessment of pollutant loading, respectively. Assessment results showed that the pollutant loadings in soil and groundwater were linearly related (r 2  = 0.64). The pollutant loadings were negatively related with zero-order and first-order decay rates in both soil (r = - 0.5 and - 0.6, respectively) and groundwater (- 1.0 and - 0.8, respectively). In addition, this study scientifically defended that the soil partitioning coefficient (K d ) significantly affected the pollutant loadings in soil (r = 0.6) and the maximum masses in groundwater (r = - 0.9). However, K d was not a representative factor for chemical transportability unlike the expectation in chemical ranking systems of soil and groundwater pollutants. The pollutant loadings estimated using a physics-based hydrogeological model provided a more rational ranking for exposure assessment, compared to the summation of persistency and transportability scores in

  9. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial.

    Directory of Open Access Journals (Sweden)

    Takeshi Nishijima

    Full Text Available BACKGROUND: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL plus ritonavir-boosted Darunavir (DRV/r in patients with suppressed viral load. METHODS: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r plus tenofovir/emtricitabine (TVD, who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR at 48 weeks calculated with Cockcroft-Gault equation. RESULTS: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD. Greater than 10% improvement in eGFR was noted in 6 (25% out of 24 with RAL+DRV/r and 3 (11% of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354. Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026. Per protocol analysis showed that the HIV-RNA was 10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load. TRIAL REGISTRATION: ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J.

  10. Experiment and simulation study on unidirectional carbon fiber composite component under dynamic 3 point bending loading

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Guowei; Sun, Qingping; Zeng, Danielle; Li, Dayong; Su, Xuming

    2018-04-10

    In current work, unidirectional (UD) carbon fiber composite hatsection component with two different layups are studied under dynamic 3 point bending loading. The experiments are performed at various impact velocities, and the effects of impactor velocity and layup on acceleration histories are compared. A macro model is established with LS-Dyna for more detailed study. The simulation results show that the delamination plays an important role during dynamic 3 point bending test. Based on the analysis with high speed camera, the sidewall of hatsection shows significant buckling rather than failure. Without considering the delamination, current material model cannot capture the post failure phenomenon correctly. The sidewall delamination is modeled by assumption of larger failure strain together with slim parameters, and the simulation results of different impact velocities and layups match the experimental results reasonable well.

  11. HIV Viral Load

    Science.gov (United States)

    ... Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed January 2016. (May 1, 2014) Guidelines for ...

  12. Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

    Science.gov (United States)

    Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

    2014-05-01

    Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P < 0.0001), but no significant correlation existed between EBV DNA levels in whole blood and enriched B-cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios. © 2013 Wiley Periodicals, Inc.

  13. Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

    Science.gov (United States)

    Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J

    2010-02-01

    The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

  14. The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients.

    Science.gov (United States)

    Haq, I-U; Dalla Pria, A; Papanastasopoulos, P; Stegmann, K; Bradshaw, D; Nelson, M; Bower, M

    2016-01-01

    The aim of the study was to evaluate the role of plasma Kaposi sarcoma herpesvirus (KSHV) as a diagnostic and prognostic biomarker in people living with HIV (PLWH) and diagnosed with KSHV-associated diseases. Using quantitative nested polymerase chain reaction (PCR) targeting the open reading frame-26 gene of KSHV, plasma levels of KSHV were measured in consecutive PLWH with KSHV-associated diseases or as part of the investigation of lymphadenopathy. Plasma KSHV assays were performed on samples from 684 PLWH and 20 HIV-seronegative people with KSHV-associated malignancies. In PLWH, plasma KSHV was detected in 39% of those with KS, 99% of those with multicentric Castleman disease (MCD), 9% of those with non-Hodgkin lymphoma (NHL), 2% of those with non-AIDS-defining malignancies and 0% of those with nonmalignant lymphadenopathy. There was no significant difference in plasma KSHV viral load among those with KS, MCD and KSHV-associated NHL. The 5-year overall survival rate from KS diagnosis of 335 PLWH was 95.2% (95% confidence interval 92.6-97.8%). Plasma KSHV viraemia did not predict overall survival in those with KS (P = 0.73), nor when those with T0 stage KS (P = 0.52) or T1 stage KS (P = 0.62) were analysed separately. Measuring the plasma levels of KSHV as a biomarker in KSHV-associated disease has a very limited value in either diagnosis or prognostication. The only potential role of clinical value is the suggestion that an undetectable plasma KSHV excludes a diagnosis of MCD in PLWH. © 2015 British HIV Association.

  15. An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study.

    Science.gov (United States)

    Damond, F; Benard, A; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente; Wainberg, Mark; Taieb, Audrey; Matheron, Sophie; Chene, Genevieve; Brun-Vezinet, Francoise

    2011-10-01

    Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.

  16. Association between pharmacy medication refill-based adherence rates and cd4 count and viral-load responses: A retrospective analysis in treatment-experienced adults with HIV.

    Science.gov (United States)

    Townsend, Mary L; Jackson, George L; Smith, Rose; Wilson, Kenneth H

    2007-04-01

    Current guidelines and most contemporary statements in the literature indicate that, like other medical conditions, HIV infection requires exceptionally high adherence to highly active antiretroviral therapy (HAART) for successful treatment. This study was conducted to determine the association between pharmacy medication refill rates-a surrogate marker for adherence to HAART- and CD4-count/viral-load responses in patients with HIV METHODS: This retrospective study was conducted at the HIV Clinic, Veterans Affairs Medical Center, Durham, North Carolina. Male and female patients aged >/=18 years with a history of HIV who attended clinic appointments on 3 consecutive clinic days were enrolled. Pharmacy medication refill-based adherence rates over the 6 months before the study were determined by examining electronic pharmacy records. The most recent viral load and the change (Delta) in CD4 count over the past year-surrogate measures of outcome-were also collected from each patient's electronic medical record and compared with refill adherence rates. The incidence of AIDS-related events and past antiretroviral experience were also compared with the DeltaCD4 count and adherence rates. Data from 58 patients were included in the study. Thirty-nine patients were black men; the mean age was 51.5 years. There was a nonsignificant correlation between 6-month pharmacy medication refillbased adherence rates and viral loads (r = 0.10). The relationship between DeltaCD4 count and adherence was complex. With adherence rates >70%, the DeltaCD4 count ranged from +414 to -238, with no indication that increasing adherence led to a greater CD4 count increase. The DeltaCD4 count progressively declined with adherence rates 70%, there was no significant correlation between adherence rates and DeltaCD4 counts or viral-load responses.

  17. Comparison of HCV viral load and its genotype distributions in HCV mono- and HIV/HCV co-infected illicit drug users

    OpenAIRE

    Jamalidoust, Marzieh; Namayandeh, Mandana; Moghadami, Mohsen; Ziyaeyan, Mazyar

    2017-01-01

    Background Because of shared modes of transmission, patients with hepatitis C virus (HCV) infection are often co-infected with other types of hepatitis viruses and/or HIV. We studied HCV viral load and its genotype patterns among HCV mono- and HCV/HIV co-infected Illicit Drug Users in Fars province-Iran. Methods Totally, 580 HCV seropositive IDUs referred to Prof. Alborzi Clinical Microbiology Research Center, Shiraz, Iran, without receiving any anti-HCV treatment, were enrolled. After their ...

  18. Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

    Science.gov (United States)

    2011-05-20

    CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV -1-infected individuals. Nat Med 14: 413–420. 12. Tan R...Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV -Infected Subjects Influence CD4 Recovery and AIDS Vincent C...Landrum2,4, Matthew J. Dolan9, Sunil K. Ahuja10,11,12, Brian Agan2, Hemant Kulkarni10,11*, the Infectious Disease Clinical Research Program (IDCRP) HIV

  19. Variation in Fetal Outcome, Viral Load and ORF5 Sequence Mutations in a Large Scale Study of Phenotypic Responses to Late Gestation Exposure to Type 2 Porcine Reproductive and Respiratory Syndrome Virus

    Science.gov (United States)

    Ladinig, Andrea; Wilkinson, Jamie; Ashley, Carolyn; Detmer, Susan E.; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

    2014-01-01

    In spite of extensive research, the mechanisms of reproductive disease associated with Porcine Reproductive and Respiratory Syndrome virus (PRRSv) are still poorly understood. The objectives of this large scale study were to evaluate associations between viral load and fetal preservation, determine the impact of type 2 PRRSv on fetal weights, and investigate changes in ORF5 PRRSv genome in dams and fetuses during a 21-day period following challenge. At gestation day 85 (±1), 114 gilts were experimentally infected with type 2 PRRSv, while 19 gilts served as reference controls. At necropsy, fetuses were categorized according to their preservation status and tissue samples were collected. PRRSv RNA concentrations were measured in gilt serum collected on days 0, 2, 6, and 21 post-infection, as well as in gilt and fetal tissues collected at termination. Fetal mortality was 41±22.8% in PRRS infected litters. Dead fetuses appeared to cluster in some litters but appeared solitary or random in others. Nine percent of surviving piglets were meconium-stained. PRRSv RNA concentration in fetal thymus, fetal serum and endometrium differed significantly across preservation category and was greatest in tissues of meconium-stained fetuses. This, together with the virtual absence of meconium staining in non-infected litters indicates it is an early pathological condition of reproductive PRRS. Viral load in fetal thymus and in fetal serum was positively associated with viral load in endometrium, suggesting the virus exploits dynamic linkages between individual maternal-fetal compartments. Point mutations in ORF5 sequences from gilts and fetuses were randomly located in 20 positions in ORF5, but neither nucleotide nor amino acid substitutions were associated with fetal preservation. PRRSv infection decreased the weights of viable fetuses by approximately 17%. The considerable variation in gilt and fetal outcomes provides tremendous opportunity for more detailed investigations of

  20. A European multicentre study on the comparison of HCV viral loads between VERIS HCV assay and COBAS® TaqMan® HCV Test and RealTime HCV Assay.

    Science.gov (United States)

    Braun, Patrick; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Micheli, Valeria; Sauné, Karine; Trimoulet, Pascale; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-05-01

    Beckman Coulter has developed the VERIS HCV Assay for use on the new fully automated DxN VERIS Molecular Diagnostic System ¥ for HCV viral load monitoring. Evaluate the clinical performance of the new quantitative VERIS HCV Assay. Comparison was performed on 279 plasma specimens from HCV infected patients tested with the VERIS HCV Assay and COBAS ® Ampliprep/COBAS ® Taqman ® HCV Test and 369 specimens tested with the VERIS HCV Assay and RealTime HCV Assay. Patient monitoring sample results from four time points were also compared. The average bias between the VERIS HCV Assay and the COBAS ® Ampliprep/COBAS ® Taqman ® HCV Test was 0.04 log 10 IU/mL, while between the VERIS HCV Assay and the RealTime HCV Assay average bias was 0.21 log 10 IU/mL. Bias, however, was not consistent across the measuring range. Analysis at the lower end of quantification levels 50, 100, and 1000IU/mL showed a predicted bias for VERIS HCV Assay versus COBAS ® Ampliprep/COBAS ® Taqman ® HCV Test between -0.42 and -0.22 log 10 IU/mL and for VERIS HCV Assay versus RealTime HCV Assay between 0.00 and 0.13 log 10 IU/mL. Patient monitoring of HCV viral load over time demonstrated similar levels between VERIS HCV Assay results and COBAS ® Ampliprep/COBAS ® Taqman ® HCV Test (52 samples from 13 patients) and RealTime HCV Assay (112 samples from 28 patients). VERIS HCV Assay for use on the DxN VERIS Molecular Diagnostic System represents a reliable new tool for easy sample to result HCV RNA viral load monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Association between human papillomavirus (HPV) 16, HPV18, and other HR-HPV viral load and the histological classification of cervical lesions: Results from a large-scale cross-sectional study.

    Science.gov (United States)

    Wu, Zeni; Qin, Yu; Yu, Lulu; Lin, Chunqing; Wang, Hong; Cui, Jianfeng; Liu, Bin; Liao, Yiqun; Warren, De'Andre; Zhang, Xun; Chen, Wen

    2017-03-01

    The relationship between HPV viral load and histological grades in the development of cervical cancer is in argument. It is helpful to better understand the association by quantitatively detecting viral load of HPV16, 18, and a pool of 12 other high-risk HPV type (OT) independently on the samples of precancer and cancer. A cross-sectional study was performed in five medical centers of China. Histological diagnosis made by local pathologists was adjudicated via a pathology expert panel. A fully automated real-time PCR test was used for the measurement of HPV16, 18, OT, and human β-globin gene. A total of 2,513 women [1,341 normal, 209 low grade intraepithelial lesion (LSIL), 392 high grade intraepithelial lesion (HSIL), 520 squamous cell carcinoma (SCC), and 51 adenocarcinoma (ADC)] were included. There is a linear increase in the total 14 HPV viral load with histological grade from normal to SCC. This trend was not observed in HPV18 infection but HPV16. The viral load for OT was low in normal, peaked in LSIL and HSIL, and declined in SCC and ADC. In the co-infection of HPV16 and HPV18, HPV16 viral load was significantly higher than HPV18 in LSIL and HSIL. In co-infection of HPV16 and OT, higher HPV16 viral load was also seen in SCC and ADC. Viral load of HPV16 increases with cervical lesion grade and is predominant in cervical cancer. HPV18 viral load is low in precancer, but going up in cancer. OT viral load shows inverse trend of HPV18. J. Med. Virol. 89:535-541, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Comparison of HCV viral load and its genotype distributions in HCV mono- and HIV/HCV co-infected illicit drug users.

    Science.gov (United States)

    Jamalidoust, Marzieh; Namayandeh, Mandana; Moghadami, Mohsen; Ziyaeyan, Mazyar

    2017-07-11

    Because of shared modes of transmission, patients with hepatitis C virus (HCV) infection are often co-infected with other types of hepatitis viruses and/or HIV. We studied HCV viral load and its genotype patterns among HCV mono- and HCV/HIV co-infected Illicit Drug Users in Fars province-Iran. Totally, 580 HCV seropositive IDUs referred to Prof. Alborzi Clinical Microbiology Research Center, Shiraz, Iran, without receiving any anti-HCV treatment, were enrolled. After their HCV infections were reconfirmed by one step rapid diagnostic test, HCV RNA level and HCV genotypes were determined by Taq-man real-time PCR assays. Their HIV serostatus was determined and seropositive patients were excluded from the group. In addition, 104 HIV/HCV co-infected IDUs referred from Shiraz Behavioral Diseases Consultation Center (SBDC) were assessed for HCV RNA level and HCV genotype patterns, as well. The overall estimated HIV prevalence was 6.7% (39/580) among HCV seropositive IDUs. Genotype 1, the most prevalent genotype in both groups, was detected in 69% and 49% of co- and mono-infected IDUs, respectively. Median HCV viral load was significantly higher in HIV/HCV co-infected patients, compared with that among HCV mono-infected counterparts. Given the higher baseline HCV viral load and GT1 attributed to poorer treatments response, HCV treatment must be more considered among HCV/HIV co-infected IDUs, compared to those mono-infected with HCV.

  3. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Theys Kristof

    2012-10-01

    Full Text Available Abstract Background The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. Conclusions These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this

  4. Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico Seroprevalencia de hepatitis C y correlación entre la carga viral y el genotipo viral en asistentes al nivel primario de atención enMéxico

    Directory of Open Access Journals (Sweden)

    Ana I Burguete-Garcia

    2011-01-01

    Full Text Available OBJECTIVE: To measure hepatitis C virus (HCV sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 % (C.I. 95% l.3-l.7, from seropositive individuals 60.9 % reported previous blood transfusion, 28.3% declared to have relatives with cirrhosis, 25.2% had tattoos or piercings, and 6.9% referred to have used drugs. Male gender and transfusion (pOBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC, la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 % (C.I. 95% l.3-l.7, 60.9% reportaron transfusion sanguinea previa, 28.3% dijo tener familiares cercanos con cirrosis, 25.2% tenian tatuajes o piercing y 6.9% refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l, fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3%. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33%; subtipo lB, 21.4% seguido por el genotipo 2 (subtipo 2A, 8.50%. Se observó una correlación positiva de 51% con la carga viral más alta y el genotipo viral 1A

  5. Assessing the impact of non-point loading on river systems: A joint German-Canada study

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, P.A.; Culp, J.M.; Wrona, F.J. [National Hydrology Research Inst., Saskatoon, Saskatchewan (Canada); Dreyer, U.; Rupp, H.; Meissner, R.; Guhr, H.

    1995-12-31

    Understanding the ecological effects of non-point sources of nutrient and contaminant loadings has become increasingly important in the management of riverine ecosystems, particularly since successes in controlling effluent emissions have resulted in the reduction of point-source loadings to rivers in industrialized nations. The federal governments of Canada and Germany recognize the need to evaluate the impact of non-point loading, particularly agricultural, on river systems since nutrients and agricultural contaminants can directly affect ecosystem structure and processes. Moreover, in Germany, the government`s target of achieving equal environmental conditions throughout its unified territory by the year 2000 has provided impetus to develop cost-effective methods for determining the effect of agricultural activity on aquatic ecosystems. The objective of this study is to combine biological, chemical and hydrological approaches for assessing non-point source loadings to rivers in Canada and the former German Democratic Republic, and to make recommendations for the design of future monitoring programs. Studies were recently initiated on small tributaries of the Elbe River, Germany, and the Athabasca River, Canada, to quantify non-point nutrient loading, identify reaches of nitrogen or phosphorus limitation, and evaluate changes in benthic algal and invertebrate communities in relation to land-use practices. Once methods have been established and validated, the project will be scaled up to large river catchment areas. This study also assesses several rapid bioassessment techniques for monitoring riverine ecosystems impacted by non-point loadings.

  6. Short-term garlic supplementation and highly active antiretroviral treatment adherence, CD4+ cell counts, and human immunodeficiency virus viral load.

    Science.gov (United States)

    Liu, Chenglong; Wang, Cuiwei; Robison, Esther; Levine, Alexandra M; Gandhi, Monica; Schwartz, Rebecca; Weber, Kathleen M; Merenstein, Daniel

    2012-01-01

    Human immunodeficiency virus (HIV)-infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic's association with antiretroviral therapies, however, even though that association is very relevant clinically. To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. The research team carried out a self-controlled, longitudinal study nested within the Women's Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the studies visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. Participants were persons using garlic supplementation who already were participants in the WIHS. The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research teams selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic

  7. Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

    Science.gov (United States)

    Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S.; Valentine, Fred

    2009-01-01

    Background A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. Methodology/Principal Findings We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log10 copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of ≥400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. Conclusion The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure. PMID:19714253

  8. A central swivel point in the RFC clamp loader controls PCNA opening and loading on DNA.

    Science.gov (United States)

    Sakato, Miho; O'Donnell, Mike; Hingorani, Manju M

    2012-02-17

    Replication factor C (RFC) is a five-subunit complex that loads proliferating cell nuclear antigen (PCNA) clamps onto primer-template DNA (ptDNA) during replication. RFC subunits belong to the AAA(+) superfamily, and their ATPase activity drives interactions between the clamp loader, the clamp, and the ptDNA, leading to topologically linked PCNA·ptDNA. We report the kinetics of transient events in Saccharomyces cerevisiae RFC-catalyzed PCNA loading, including ATP-induced RFC activation, PCNA opening, ptDNA binding, ATP hydrolysis, PCNA closing, and PCNA·ptDNA release. This detailed perspective enables assessment of individual RFC-A, RFC-B, RFC-C, RFC-D, and RFC-E subunit functions in the reaction mechanism. Functions have been ascribed to RFC subunits previously based on a steady-state analysis of 'arginine-finger' ATPase mutants; however, pre-steady-state analysis provides a different view. The central subunit RFC-C serves as a critical swivel point in the clamp loader. ATP binding to this subunit initiates RFC activation, and the clamp loader adopts a spiral conformation that stabilizes PCNA in a corresponding open spiral. The importance of RFC subunit response to ATP binding decreases as RFC-C>RFC-D>RFC-B, with RFC-A being unnecessary. RFC-C-dependent activation of RFC also enables ptDNA binding, leading to the formation of the RFC·ATP·PCNA(open)·ptDNA complex. Subsequent ATP hydrolysis leads to complex dissociation, with RFC-D activity contributing the most to rapid ptDNA release. The pivotal role of the RFC-B/C/D subunit ATPase core in clamp loading is consistent with the similar central location of all three ATPase active subunits of the Escherichia coli clamp loader. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Digitally Controlled Point of Load Converter with Very Fast Transient Response

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2007-01-01

    voltage mode control and very fast transient response. The DiSOM modulator is combined with a digital PID compensator algorithm is implemented in a hybrid CPLD/FPGA and is used to control a synchronous Buck converter, which is used in typical Point of Load applications. The computational time is only...... and comparator the DiSOM modulator allows the sampling frequency of the output voltage control loop to be higher than the switching frequency of the power converter, typically a DC/DC converter. The features of the DiSOM modulator makes it possible to design a digitally controlled DC/DC converter with linear...... three clock cycles from the time the A/D converter result is read by the control algorithm to the time the duty cycle command is updated. A typical POL converter has been built and the experimental results show that the transient response of the converter is very fast. The output voltage overshoot...

  10. Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles.

    Science.gov (United States)

    Lee, Jong-Hwan; Seo, Hyuk Seong; Kwon, Jung-Hyuk; Kim, Hee-Tae; Kwon, Koo Chul; Sim, Sang Jun; Cha, Young Joo; Lee, Jeewon

    2015-07-15

    Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Loss of correlation between HIV viral load and CD4+ T-cell counts in HIV/HTLV-1 co-infection in treatment naive Mozambican patients.

    Science.gov (United States)

    Bhatt, N B; Gudo, E S; Semá, C; Bila, D; Di Mattei, P; Augusto, O; Garsia, R; Jani, I V

    2009-12-01

    Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction.

  12. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.

    Science.gov (United States)

    Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles

    2015-01-01

    Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

  13. Some points of the X-ray pattern of acute viral primary pneumonia caused by acute respiratory disease viruses

    International Nuclear Information System (INIS)

    Stoyanov, V.

    1991-01-01

    An analysis is made of the results of the X-ray studies as well as of the virological and serological tests in 225 out-patients consulted in the first days of their complaints. A predominance of the viral (70.2%) over the viral-bacterial primary pneumonia is established. The acute viral primary pneumonia are caused mostly by single influenza viruses and more rarely - by single respiratory viruses; in the cases of combined influenza viruses influenza-influenza viruses prevail over the influenza-respiratory ones. The morphological changes in pneumonia due to isolated single influenza viruses involve mostly the interstitium and are projected on X-ray as patchy and stripped densities. The inflamatory changes in pneumonia caused by combined influenza viruses affect both ihe interstitium and the broncho-alveolar substrate of the lungs; they are manifested in two roentgenologic forms: creeping (migrating) and fusing (confluent). In viral-bacterial pneumonia the changes affect mostly the lobe. The right lung and the lower parts of the both lungs are affected in most cases. 5 figs., 21 refs

  14. Vacinação contra influenza em crianças infectadas pelo HIV: alterações imunológicas e na carga viral Influenza vaccination in HIV infected children: immunologic and viral load changes

    Directory of Open Access Journals (Sweden)

    Aroldo P. de Carvalho

    2003-02-01

    ças com condição clínica e imunológica não estável, principalmente se essas não estiverem sob terapêutica anti-retroviral eficaz.Objective: to identify whether influenza immunization in HIV infected children could increase HIV viral load and decrease CD4+ lymphocytes count as a consequence of the response induced by a T cell-dependent antigen. Methods: prospective, descriptive study, with 51 HIV infected children, vaccinated against influenza in 1999, in Florianópolis, Brazil. Blood samples were collected at three different moments: on the immunization day; between 14 and 20 days later; between 60 and 90 days later. Plasma levels of HIV viral load and CD4+ lymphocytes count were determined. Friedman ANOVA test, Student t-test for dependent samples, Bonferroni correction, and Wilcoxon matched test were performed for statistic analysis. Results: children's mean age was 6.08 years (1 to 12.9 years. The medians of CD4+ lymphocyte count on vaccination day and at the other two moments were 789, 645 and 768 cells/mm³, respectively. A significant reduction was observed in the CD4+ lymphocyte count between the first and the second analyses, but the same did not happen between the first and the third analyses. There was no significant difference of CD4+ lymphocyte percentage between the first and the second analyses. The median of HIV viral load values in log10 copies/ml was 4.38, 4.30 and 4.25, at the three moments respectively. Eight out of 44 patients (18.2% showed increase > 0.5 log10 copies/ml in HIV viral load between the first and the second analyses and among these, four returned to levels close to their base levels in the third analysis. Conclusion: there was no significant change in the CD4+ lymphocyte percentage, in spite of a transitory increase in HIV viral load after influenza vaccination. Caution should be used when administering vaccine against flu to children with no stable clinical and immunological conditions, mainly if they are not under effective anti

  15. The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Médecins Sans Frontières (MSF) Ebola Case Management Centre (CMC), Kailahun, Sierra Leone, June -October, 2014.

    LENUS (Irish Health Repository)

    Fitzpatrick, Gabriel

    2015-05-22

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270\\/525). Ebola viral load (whole blood sample) data was available on 76% (397\\/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  16. Isolation of dengue virus serotype 4 genotype II from a patient with high viral load and a mixed Th1/Th17 inflammatory cytokine profile in South Brazil.

    Science.gov (United States)

    Kuczera, Diogo; Bavia, Lorena; Mosimann, Ana Luiza Pamplona; Koishi, Andrea Cristine; Mazzarotto, Giovanny Augusto Camacho Antevere; Aoki, Mateus Nóbrega; Mansano, Ana Maria Ferrari; Tomeleri, Ediléia Inês; Costa Junior, Wilson Liuti; Miranda, Milena Menegazzo; Lo Sarzi, Maria; Pavanelli, Wander Rogério; Conchon-Costa, Ivete; Duarte Dos Santos, Claudia Nunes; Bordignon, Juliano

    2016-06-06

    We report the isolation and characterization of dengue virus (DENV) serotype 4 from a resident of Santa Fé, state of Paraná, South Brazil, in March 2013. This patient presented with hemorrhagic manifestations, high viral load and, interestingly, a mixed Th1/Th17 cytokine profile. The patient presented with classical dengue symptoms, such as fever, rash, myalgia, arthralgia, and hemorrhagic manifestations including petechiae, gum bleeding and a positive tourniquet test result. A serum sample obtained 1 day after the initial appearance of clinical symptoms was positive for NS1 viral antigen, but this sample was negative for both IgM and IgG against DENV. Dengue virus infection was confirmed by isolation of the virus from C6/36 cells, and dengue virus serotyping was performed via one-step RT-PCR. The infection was confirmed to be caused by a serotype 4 dengue virus. Additionally, based on multiple alignment and phylogeny analyses of its complete genome sequence, the viral strain was classified as genotype II (termed LRV13/422). Moreover, a mixed Th1/Th17 cytokine profile was detected in the patient's serum, and this result demonstrated significant inflammation. Biological characterization of the virus via in vitro assays comparing LRV13/422 with a laboratory-adapted reference strain of dengue virus serotype 4 (TVP/360) showed that LRV13/422 infects both vertebrate and invertebrate cell lines more efficiently than TVP/360. However, LRV13/422 was unable to inhibit type I interferon responses, as suggested by the results obtained for other dengue virus strains. Furthermore, LRV13/422 is the first completely sequenced serotype 4 dengue virus isolated in South Brazil. The high viral load and mixed Th1/Th17 cytokine profile observed in the patient's serum could have implications for the development of the hemorrhagic signs observed, and these potential relationships can now be further studied using suitable animal models and/or in vitro systems.

  17. Modeling hydrology, groundwater recharge and non-point nitrate loadings in the Himalayan Upper Yamuna basin.

    Science.gov (United States)

    Narula, Kapil K; Gosain, A K

    2013-12-01

    The mountainous Himalayan watersheds are important hydrologic systems responsible for much of the water supply in the Indian sub-continent. These watersheds are increasingly facing anthropogenic and climate-related pressures that impact spatial and temporal distribution of water availability. This study evaluates temporal and spatial distribution of water availability including groundwater recharge and quality (non-point nitrate loadings) for a Himalayan watershed, namely, the Upper Yamuna watershed (part of the Ganga River basin). The watershed has an area of 11,600 km(2) with elevation ranging from 6300 to 600 m above mean sea level. Soil and Water Assessment Tool (SWAT), a physically-based, time-continuous model, has been used to simulate the land phase of the hydrological cycle, to obtain streamflows, groundwater recharge, and nitrate (NO3) load distributions in various components of runoff. The hydrological SWAT model is integrated with the MODular finite difference groundwater FLOW model (MODFLOW), and Modular 3-Dimensional Multi-Species Transport model (MT3DMS), to obtain groundwater flow and NO3 transport. Validation of various modules of this integrated model has been done for sub-basins of the Upper Yamuna watershed. Results on surface runoff and groundwater levels obtained as outputs from simulation show a good comparison with the observed streamflows and groundwater levels (Nash-Sutcliffe and R(2) correlations greater than +0.7). Nitrate loading obtained after nitrification, denitrification, and NO3 removal from unsaturated and shallow aquifer zones is combined with groundwater recharge. Results for nitrate modeling in groundwater aquifers are compared with observed NO3 concentration and are found to be in good agreement. The study further evaluates the sensitivity of water availability to climate change. Simulations have been made with the weather inputs of climate change scenarios of A2, B2, and A1B for end of the century. Water yield estimates under

  18. Modeling hydrology, groundwater recharge and non-point nitrate loadings in the Himalayan Upper Yamuna basin

    International Nuclear Information System (INIS)

    Narula, Kapil K.; Gosain, A.K.

    2013-01-01

    The mountainous Himalayan watersheds are important hydrologic systems responsible for much of the water supply in the Indian sub-continent. These watersheds are increasingly facing anthropogenic and climate-related pressures that impact spatial and temporal distribution of water availability. This study evaluates temporal and spatial distribution of water availability including groundwater recharge and quality (non-point nitrate loadings) for a Himalayan watershed, namely, the Upper Yamuna watershed (part of the Ganga River basin). The watershed has an area of 11 600 km 2 with elevation ranging from 6300 to 600 m above mean sea level. Soil and Water Assessment Tool (SWAT), a physically-based, time-continuous model, has been used to simulate the land phase of the hydrological cycle, to obtain streamflows, groundwater recharge, and nitrate (NO 3 ) load distributions in various components of runoff. The hydrological SWAT model is integrated with the MODular finite difference groundwater FLOW model (MODFLOW), and Modular 3-Dimensional Multi-Species Transport model (MT3DMS), to obtain groundwater flow and NO 3 transport. Validation of various modules of this integrated model has been done for sub-basins of the Upper Yamuna watershed. Results on surface runoff and groundwater levels obtained as outputs from simulation show a good comparison with the observed streamflows and groundwater levels (Nash–Sutcliffe and R 2 correlations greater than + 0.7). Nitrate loading obtained after nitrification, denitrification, and NO 3 removal from unsaturated and shallow aquifer zones is combined with groundwater recharge. Results for nitrate modeling in groundwater aquifers are compared with observed NO 3 concentration and are found to be in good agreement. The study further evaluates the sensitivity of water availability to climate change. Simulations have been made with the weather inputs of climate change scenarios of A2, B2, and A1B for end of the century. Water yield estimates

  19. Comparison of Auditory Brainstem Response in HIV-1 exposed and unexposed newborns and their correlation with the maternal viral load and CD4 cell counts

    Science.gov (United States)

    FASUNLA, Ayotunde James; OGUNBOSI, Babatunde Oluwatosin; ODAIBO, Georgina Njideka; NWAORGU, Onyekwere George Benjamin; TAIWO, Babafemi; OLALEYE, David Olufemi; OSINUSI, Kikelomo; MURPHY, Robert Leo; ADEWOLE, Isaac Folorunso; AKINYINKA, Olusegun Olusina

    2014-01-01

    Objective The effects of maternal HIV infection and antiretroviral therapy on hearing of HIV-exposed newborns in sub-Saharan Africa have not been investigated. We determined the prevalence of sensorineural hearing loss among HIV-exposed newborns and the association between the hearing threshold and maternal & newborn parameters. Design A cohort audiometric study of newborns between October 2012 and April 2013. Settings Secondary and tertiary hospital based study. Participants Consecutive 126 HIV-exposed and 121 HIV-unexposed newborns. Intervention Hearing screening of the newborns were done with Auditory Brainstem Response and compared with maternal HAART, CD4 cell counts, RNA viral loads and newborn CD4 percent. Main outcome measure Hearing threshold levels of both groups were measured and analyzed. Results 11.1% of HIV-exposed and 6.6% of unexposed newborns had hearing impairment (p=0.2214). 6.4% of HIV-exposed and 2.5% HIV-unexposed newborns had hearing threshold >20dBHL (p = 0.1578). There was no significant association between the hearing thresholds of HIV-exposed newborns and maternal CD4 cell counts (p = 0.059) but there was with maternal viral load (p=0.034). There was significant difference between the hearing thresholds of HIV-exposed newborns with CD4 % of ≤25 and >25. This study showed significant difference in the hearing of the 119 HAART-exposed newborns and 7 unexposed newborns (p=0.002; RR=0.13 [0.05–0.32]). Conclusion There was a trend towards more hearing loss in HIV-exposed newborns. However, hearing thresholds increase with increasing mothers’ viral load. This background information supports the need for further studies on the role of in-utero exposure to HIV and HAART in newborn hearing loss. PMID:25313584

  20. Reflecting the real value of health care resources in modelling and cost-effectiveness studies-The example of viral load informed differentiated care.

    Science.gov (United States)

    Revill, Paul; Walker, Simon; Cambiano, Valentina; Phillips, Andrew; Sculpher, Mark J

    2018-01-01

    The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter's value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest gains in population health. The findings have

  1. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia

    NARCIS (Netherlands)

    de Jong, Menno D.; Simmons, Cameron P.; Thanh, Tran Tan; Hien, Vo Minh; Smith, Gavin J. D.; Chau, Tran Nguyen Bich; Hoang, Dang Minh; Chau, Nguyen Van Vinh; Khanh, Truong Huu; Dong, Vo Cong; Qui, Phan Tu; Cam, Bach Van; Ha, Do Quang; Guan, Yi; Peiris, J. S. Malik; Chinh, Nguyen Tran; Hien, Tran Tinh; Farrar, Jeremy

    2006-01-01

    Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine

  2. Experimental and theoretical analyses of package-on-package structure under three-point bending loading

    International Nuclear Information System (INIS)

    Jia Su; Wang Xi-Shu; Ren Huai-Hui

    2012-01-01

    High density packaging is developing toward miniaturization and integration, which causes many difficulties in designing, manufacturing, and reliability testing. Package-on-Package (PoP) is a promising three-dimensional high-density packaging method that integrates a chip scale package (CSP) in the top package and a fine-pitch ball grid array (FBGA) in the bottom package. In this paper, in-situ scanning electron microscopy (SEM) observation is carried out to detect the deformation and damage of the PoP structure under three-point bending loading. The results indicate that the cracks occur in the die of the top package, then cause the crack deflection and bridging in the die attaching layer. Furthermore, the mechanical principles are used to analyse the cracking process of the PoP structure based on the multi-layer laminating hypothesis and the theoretical analysis results are found to be in good agreement with the experimental results. (condensed matter: structural, mechanical, and thermal properties)

  3. Investigation on the Performance of UPQC-Q for Voltage Sag Mitigation and PQ Improvement at a Critical Load Point

    OpenAIRE

    Basu, Malabika; Das, S. P.; Dubey, Gopal

    2008-01-01

    The unified power quality conditioner (UPQC) is one of the major custom power solutions, which is capable of mitigating the effect of supply voltage sag at the load end or at the point of common coupling (PCC) in a distributed network. It also prevents the propagation of the load current harmonics to the utility and improves the input power factor of the load. The control of series compensator (SERC) of the UPQC is such that it injects voltage in quadrature advance to the supply current. Thus...

  4. Estimation of non-point source pollution loads by improvising export coefficient model in watershed with a modified planting pattern

    Science.gov (United States)

    Dong, F.; Liu, X. B.; Peng, W. Q.; Wang, L.

    2017-08-01

    Export coefficient model was improved to calculate and compare non-point source pollution loads in an agricultural watershed before and after implanting new cropping pattern. The modification was done by introducing the reduction coefficient in consumption amount and loss load as well as the proportion of bioactive ingredients of fertilizer and pesticide to the export coefficient model developed by Johnes in 1996. The modified export coefficient model was then applied to estimate non-point source pollution load in Gaoxi community, Yunnan Province, China where a water-saving and emission reduction technology was implemented by changing cropping pattern. Study results showed that the improved export coefficient model had a favorable flexibility in calculating the non-point source pollution loads and well applicable to the watersheds where various input data is in short. Moreover, the findings will provide scientific basis to understand the variability of non-point source pollutants in agricultural watersheds and their load estimation in order to optimize the efficiency of pollutants reduction plan implemented through agricultural adjustment.

  5. Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment Comparação longitudinal entre cargas virais seminais e plasmáticas do HIV-1 durante terapia anti-retroviral

    Directory of Open Access Journals (Sweden)

    Lauro Ferreira da Silva Pinto Neto

    2003-12-01

    Full Text Available This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21. Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma and 3.2 log10 copies/ml (semen. At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.Este estudo foi desenhado para investigar o impacto do tratamento com anti-retrovirais na evolução das cargas virais plasmáticas e seminais do HIV-1. A carga viral do HIV-1 e a contagem de linfócitos T CD4+ e CD8+ foi determinada em amostras pareadas de sangue e sêmen de 36 pacientes virgem de tratamento nos dias 0, 45, 90 e 180 após o início da terapia. As curvas de declínio das cargas virais plasmática e seminal foram semelhantes (p= 0.21. As medianas da carga viral plasmática e seminal no pré-tratamento (dia 0 foram 4.95 e 4.48 log10 cópias/ml, respectivamente. Seis meses após o início da terapia, a mediana da carga viral plasmática era 3.15 log10 cópias/ml e a seminal 3.2 log10 cópias/ml. Neste mesmo periodo, 22 pacientes apresentavam carga viral abaixo de 400 cópias/ml no plasma e/ou sêmen, enquanto apenas 9 pacientes apresentavam carga viral abaixo do limite de detecção nos dois compartimentos.

  6. Planetary Load Sharing in Three-Point Mounted Wind Turbine Gearboxes: A Design and Test Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Jonathan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Guo, Yi [National Renewable Energy Lab. (NREL), Golden, CO (United States); Zhang, Zhiwei [Romax InSight, Nottingham, (United Kingdom); Lucas, Doug [The Timken Company, Jackson Township, OH (United States)

    2017-04-06

    This work compares the planetary load-sharing characteristics of wind turbine gearboxes supported by cylindrical roller bearings (CRBs) and preloaded tapered roller bearings (TRBs) when subjected to rotor moments. Planetary bearing loads were measured in field-representative dynamometer tests and compared to loads predicted by finite-element models. Preloaded TRBs significantly improved load sharing. In pure torque conditions, the upwind planet bearing load in the gearbox with preloaded TRBs was only 14% more than the assumed load compared to 47% more for the gearbox with CRBs. Consequently, the predicted fatigue life of the complete set of planetary bearings for the gearbox with preloaded TRBs is 3.5 times greater than that of the gearbox with CRBs.

  7. Modeling hydrology, groundwater recharge and non-point nitrate loadings in the Himalayan Upper Yamuna basin

    Energy Technology Data Exchange (ETDEWEB)

    Narula, Kapil K., E-mail: kkn2104@columbia.edu [Columbia Water Center (India Office), Columbia University, New Delhi 110 016 (India); Gosain, A.K. [Department of Civil Engineering, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110 016 (India)

    2013-12-01

    The mountainous Himalayan watersheds are important hydrologic systems responsible for much of the water supply in the Indian sub-continent. These watersheds are increasingly facing anthropogenic and climate-related pressures that impact spatial and temporal distribution of water availability. This study evaluates temporal and spatial distribution of water availability including groundwater recharge and quality (non-point nitrate loadings) for a Himalayan watershed, namely, the Upper Yamuna watershed (part of the Ganga River basin). The watershed has an area of 11 600 km{sup 2} with elevation ranging from 6300 to 600 m above mean sea level. Soil and Water Assessment Tool (SWAT), a physically-based, time-continuous model, has been used to simulate the land phase of the hydrological cycle, to obtain streamflows, groundwater recharge, and nitrate (NO{sub 3}) load distributions in various components of runoff. The hydrological SWAT model is integrated with the MODular finite difference groundwater FLOW model (MODFLOW), and Modular 3-Dimensional Multi-Species Transport model (MT3DMS), to obtain groundwater flow and NO{sub 3} transport. Validation of various modules of this integrated model has been done for sub-basins of the Upper Yamuna watershed. Results on surface runoff and groundwater levels obtained as outputs from simulation show a good comparison with the observed streamflows and groundwater levels (Nash–Sutcliffe and R{sup 2} correlations greater than + 0.7). Nitrate loading obtained after nitrification, denitrification, and NO{sub 3} removal from unsaturated and shallow aquifer zones is combined with groundwater recharge. Results for nitrate modeling in groundwater aquifers are compared with observed NO{sub 3} concentration and are found to be in good agreement. The study further evaluates the sensitivity of water availability to climate change. Simulations have been made with the weather inputs of climate change scenarios of A2, B2, and A1B for end of the

  8. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Hsuen-Wen Chang

    Full Text Available Hand-foot-mouth diseases (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16 as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype. This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  9. Increase in transaminase levels following the use of raltegravir in a woman with a high HIV viral load at 35 weeks of pregnancy.

    Science.gov (United States)

    Renet, Sophie; Closon, Aurélie; Brochet, Marie-Sophie; Bussières, Jean-François; Boucher, Marc

    2013-01-01

    Despite the efficacy of raltegravir in reducing viral load in HIV-infected patients, evidence for its safety in late pregnancy is lacking. A high rate of placental transfer was recently demonstrated. A treatment-naïve 34-year-old HIV-1-positive woman of African origin began treatment with zidovudine/lamivudine, lopinavir/ritonavir, and raltegravir at 35 weeks of pregnancy. After 11 days of treatment with raltegravir, a substantial reduction in viral load was achieved. Concurrently, she had a 23-fold increase in serum alanine aminotransferase and a 10-fold increase in serum aspartate aminotransferase, both of which returned to normal when raltegravir treatment was discontinued. A healthy boy was delivered at term. The infant's tests for HIV were negative at five months, and he had no health problems at eight months. This is the first case report, to our knowledge, of increased maternal serum transaminase levels following the use of raltegravir in a woman at a late stage of pregnancy.

  10. Prevalence of Howell-Jolly body-like inclusions in HIV patients and their correlation with CD4 counts and HIV RNA viral load.

    Science.gov (United States)

    Chang, Brian; Huang, Richard Sheng Poe; Dasgupta, Amitava; Nguyen, Nghia; Wahed, Amer

    2015-01-01

    Previous reports have described the rare occurrence of detached nuclear fragments resembling Howell-Jolly bodies within neutrophils from HIV patients, organ-transplant recipients, and patients on immunosuppressive drugs. To date, their potential clinical significance is unknown, and pathologists tend to disregard their presence. Our study sought to find a correlation between these inclusions and the overall disease state, specifically within the HIV patient population. Eighty-three peripheral smears, all from different patients, were examined for the presence of inclusions and compared with recent CD4 counts and HIV RNA viral loads. Six cases contained inclusions, yielding a prevalence of 7.2%. These six patients had a mean CD4 count of 546±305 cells/μL compared to 247±242 cells/μL in those lacking inclusions (pHowell-Jolly body-like inclusions may be viewed as a potential biomarker indicative of a low risk for disease progression and/or good response to therapy based upon higher CD4 counts and relatively favorable viral loads. © 2015 by the Association of Clinical Scientists, Inc.

  11. Molecular dissection of a viral quasispecies under mutagenic treatment: positive correlation between fitness loss and mutational load.

    Science.gov (United States)

    Arias, Armando; Isabel de Ávila, Ana; Sanz-Ramos, Marta; Agudo, Rubén; Escarmís, Cristina; Domingo, Esteban

    2013-04-01

    Low fidelity replication and the absence of error-repair activities in RNA viruses result in complex and adaptable ensembles of related genomes in the viral population, termed quasispecies, with important implications for natural infections. Theoretical predictions suggested that elevated replication error rates in RNA viruses might be near to a maximum compatible with viral viability. This fact encouraged the use of mutagenic nucleosides as a new antiviral strategy to induce viral extinction through increased replication error rates. Despite extensive evidence of lethal mutagenesis of RNA viruses by different mutagenic compounds, a detailed picture of the infectivity of individual genomes and its relationship with the mutations accumulated is lacking. Here, we report a molecular analysis of a foot-and-mouth disease virus population previously subjected to heavy mutagenesis to determine whether a correlation between increased mutagenesis and decreased fitness existed. Plaque-purified viruses isolated from a ribavirin-treated quasispecies presented decreases of up to 200-fold in infectivity relative to clones in the reference population, associated with an overall eightfold increase in the mutation frequency. This observation suggests that individual infectious genomes of a quasispecies subjected to increased mutagenesis lose infectivity by their continuous mutagenic 'poisoning'. These results support the lethal defection model of virus extinction and the practical use of chemical mutagens as antiviral treatment. Even when extinction is not achieved, mutagenesis can decrease the infectivity of surviving virus, and facilitate their clearance by host immune responses or complementing antiviral approaches.

  12. The dual CCR5 and CCR2 inhibitor cenicriviroc does not redistribute HIV into extracellular space: implications for plasma viral load and intracellular DNA decline.

    Science.gov (United States)

    Kramer, Victor G; Hassounah, Said; Colby-Germinario, Susan P; Oliveira, Maureen; Lefebvre, Eric; Mesplède, Thibault; Wainberg, Mark A

    2015-03-01

    Cenicriviroc is a potent antagonist of the chemokine coreceptors 5 and 2 (CCR5/CCR2) and blocks HIV-1 entry. The CCR5 inhibitor maraviroc has been shown in tissue culture to be able to repel cell-free virions from the cell surface into extracellular space. We hypothesized that cenicriviroc might exhibit a similar effect, and tested this using clinical samples from the Phase IIb study 652-2-202, by measuring rates of intracellular DNA decline. We also monitored viral RNA levels in culture fluids. We infected PM-1 cells with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of cenicriviroc (20 nM) or maraviroc (50 nM) or controls. Viral load levels and p24 were measured by ELISA, quantitative PCR and quantitative real-time reverse transcription PCR at 4 h post-infection. Frozen PBMC DNA samples from 30 patients with virological success in the Phase IIb study were studied, as were early and late reverse transcript levels. Docking studies compared binding between cenicriviroc/CCR5 and maraviroc/CCR5. Unlike maraviroc, cenicriviroc did not cause an increase in the amount of virus present in culture fluids at 4 h compared with baseline. The use of cenicriviroc did, however, result in lower levels of intracellular viral DNA after 4 h. Structural modelling indicates that cenicriviroc binds more deeply than maraviroc to the hydrophobic pocket of CCR5, providing an explanation for the absence of viral rebound with cenicriviroc. In contrast to maraviroc, cenicriviroc does not repel virus back into extracellular space. Differences in results may be due to superior binding of cenicriviroc to CCR5 compared with maraviroc. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    International Nuclear Information System (INIS)

    Zhang, Donghong; Zhang, Qingying; Zhou, Li; Huo, Leijun; Zhang, Yi; Shen, Zhongying; Zhu, Yi

    2010-01-01

    Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC

  14. Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients.

    Science.gov (United States)

    Vidales-Braz, Beatris Maria; da Silva, Naylê Maria Oliveira; Lobato, Rubens; Germano, Fabiana Nunes; da Mota, Luiza Dias; Barros, Elvino J G; de Martinez, Ana Maria Barral

    2015-02-03

    Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world's population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the dialyzer membrane.

  15. [Estimation of urban non-point source pollution loading and its factor analysis in the Pearl River Delta].

    Science.gov (United States)

    Liao, Yi-Shan; Zhuo, Mu-Ning; Li, Ding-Qiang; Guo, Tai-Long

    2013-08-01

    In the Pearl Delta region, urban rivers have been seriously polluted, and the input of non-point source pollution materials, such as chemical oxygen demand (COD), into rivers cannot be neglected. During 2009-2010, the water qualities at eight different catchments in the Fenjiang River of Foshan city were monitored, and the COD loads for eight rivulet sewages were calculated in respect of different rainfall conditions. Interesting results were concluded in our paper. The rainfall and landuse type played important roles in the COD loading, with greater influence of rainfall than landuse type. Consequently, a COD loading formula was constructed that was defined as a function of runoff and landuse type that were derived SCS model and land use map. Loading of COD could be evaluated and predicted with the constructed formula. The mean simulation accuracy for single rainfall event was 75.51%. Long-term simulation accuracy was better than that of single rainfall. In 2009, the estimated COD loading and its loading intensity were 8 053 t and 339 kg x (hm2 x a)(-1), and the industrial land was regarded as the main source of COD pollution area. The severe non-point source pollution such as COD in Fenjiang River must be paid more attention in the future.

  16. On the multiplicity effect of an m-fold moving point load on the ...

    African Journals Online (AJOL)

    In this work the response of an elastic beam supported by viscoelastic foundation (Winkler Model) to an external excitation (force) is investigated with particular attention to the efect of the excitation by a multipple cyclic moving load. The effect of the multiplicity of the cyclic - moving load with respect to the amplitude of ...

  17. Operation and thermal loading of three-level Neutral-Point-Clamped wind power converter under various grid faults

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede; Liserre, Marco

    2012-01-01

    Ride Through (LVRT) operation under grid faults, may compromise the reliability of the system and consequently further increase its cost. In this paper, the impact of various grid faults on a three-level Neutral-Point-Clamped (3L-NPC) grid-converter in terms of thermal loading of power semiconductor...

  18. Planetary Load Sharing in Three-Point-Mounted Wind Turbine Gearboxes: A Design and Test Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yi; Keller, Jonathan; Zhang, Zhiwei; Lucas, Doug

    2017-03-08

    The planetary load sharing characteristics of wind turbine gearboxes supported by cylindrical roller bearings (CRBs) and preloaded tapered roller bearings (TRBs) when subjected to rotor moments are compared in this work. Planetary bearing loads were measured in field-representative dynamometer tests and compared to loads predicted by finite-element models. Load sharing was significantly improved with preloaded TRBs. In pure torque conditions, the upwind planet bearing loads in the gearbox with preloaded TRBs were a maximum of 1.14 compared to 1.47 in the gearbox with CRBs. Consequently, the predicted fatigue life of the complete set of planetary bearings for the gearbox with preloaded TRBs is 3.5 times greater than that of the gearbox with CRBs.

  19. Application of dual-cloud point extraction for the trace levels of copper in serum of different viral hepatitis patients by flame atomic absorption spectrometry: a multivariate study.

    Science.gov (United States)

    Arain, Salma Aslam; Kazi, Tasneem G; Afridi, Hassan Imran; Abbasi, Abdul Rasool; Panhwar, Abdul Haleem; Naeemullah; Shanker, Bhawani; Arain, Mohammad Balal

    2014-12-10

    An efficient, innovative preconcentration method, dual-cloud point extraction (d-CPE) has been developed for the extraction and preconcentration of copper (Cu(2+)) in serum samples of different viral hepatitis patients prior to couple with flame atomic absorption spectrometry (FAAS). The d-CPE procedure was based on forming complexes of elemental ions with complexing reagent 1-(2-pyridylazo)-2-naphthol (PAN), and subsequent entrapping the complexes in nonionic surfactant (Triton X-114). Then the surfactant rich phase containing the metal complexes was treated with aqueous nitric acid solution, and metal ions were back extracted into the aqueous phase, as second cloud point extraction stage, and finally determined by flame atomic absorption spectrometry using conventional nebulization. The multivariate strategy was applied to estimate the optimum values of experimental variables for the recovery of Cu(2+) using d-CPE. In optimum experimental conditions, the limit of detection and the enrichment factor were 0.046μgL(-1) and 78, respectively. The validity and accuracy of proposed method were checked by analysis of Cu(2+) in certified sample of serum (CRM) by d-CPE and conventional CPE procedure on same CRM. The proposed method was successfully applied to the determination of Cu(2+) in serum samples of different viral hepatitis patients and healthy controls. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Retrospective results of implants for partially edentulous posterior jaws according to time points of early loading.

    Science.gov (United States)

    Kim, Jong-Hwa; Yang, Jin-Yong; Kim, Young-Kyun; Heo, Young-Ku; Yeo, In-Sung

    2013-01-01

    This study evaluated the survival and success rates and marginal bone loss conditions of early loaded implants in the posterior maxilla and mandible of partially edentulous patients. Implants (n = 299) were placed in 105 patients at two research centers. Provisional fixed dental prostheses were provided to the patients between 1 week and 2 months after implant placement. The implants were classified into four groups according to the loading time (1 to 2, 2 to 4, 4 to 6, and 6 to 8 weeks). Periapical radiographs were taken via a parallel imaging technique, and the peri-implant marginal bone level was measured on the radiographic images. Most implants were lost within 1 month, and one implant was removed at 36 days after loading. The cumulative survival rate of the implants was 97.0%. Implants loaded in the maxilla at 1 to 2 weeks after prosthesis insertion had significantly lower survival rates than any other group (P = .013). There were no significant differences in marginal bone levels among the implant groups classified according to loading time. Early loading is a safe and predictable procedure for implant-supported restoration of posterior partial edentulism. However, care must be taken in early loading within 2 weeks after maxillary implant insertion.

  1. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Science.gov (United States)

    Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D

    2018-01-01

    HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  2. High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy in pregnancy in the Mma Bana study, Botswana.

    Science.gov (United States)

    Powis, Kathleen M; McElrath, Thomas F; Hughes, Michael D; Ogwu, Anthony; Souda, Sajini; Datwyler, Saul A; von Widenfelt, Erik; Moyo, Sikhulile; Nádas, Marisa; Makhema, Joseph; Machakaire, Esther; Lockman, Shahin; Essex, Max; Shapiro, Roger L

    2013-04-15

    Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after highly active antiretroviral therapy (HAART) initiation have not been studied. The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts ≥ 200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression. Plasma samples drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1). Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia (odds ratio: 5.8, 95% confidence interval: 1.8 to 19.4, P = 0.004). Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not (130 vs 992 pg/mL, P = 0.001; 17.5 vs 9.4 pg/mL, P = 0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women. Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment.

  3. Synthetic antibodies and peptides recognizing progressive multifocal leukoencephalopathy-specific point mutations in polyomavirus JC capsid viral protein 1.

    Science.gov (United States)

    Chen, Gang; Gorelik, Leonid; Simon, Kenneth J; Pavlenco, Alevtina; Cheung, Anne; Brickelmaier, Margot; Chen, Ling Ling; Jin, Ping; Weinreb, Paul H; Sidhu, Sachdev S

    2015-01-01

    Polyomavirus JC (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal brain disease that afflicts a small fraction of the immune-compromised population, including those affected by AIDS and transplantation recipients on immunosuppressive drug therapy. Currently there is no specific therapy for PML. The major capsid viral protein 1 (VP1) involved in binding to sialic acid cell receptors is believed to be a key player in pathogenesis. PML-specific mutations in JCV VP1 sequences present at the binding pocket of sialic acid cell receptors, such as L55F and S269F, abolish sialic acid recognition and might favor PML onset. Early diagnosis of these PML-specific mutations may help identify patients at high risk of PML, thus reducing the risks associated with immunosuppressive therapy. As a first step in the development of such early diagnostic tools, we report identification and characterization of affinity reagents that specifically recognize PML-specific mutations in VP1 variants using phage display technology. We first identified 2 peptides targeting wild type VP1 with moderate specificity. Fine-tuning via selection of biased libraries designed based on 2 parental peptides yielded peptides with different, yet still moderate, bindinspecificities. In contrast, we had great success in identifying synthetic antibodies that recognize one of the PML-specific mutations (L55F) with high specificity from the phage-displayed libraries. These peptides and synthetic antibodies represent potential candidates for developing tailored immune-based assays for PML risk stratification in addition to complementing affinity reagents currently available for the study of PML and JCV.

  4. A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa.

    Science.gov (United States)

    Huerga, Helena; Shiferie, Fisseha; Grebe, Eduard; Giuliani, Ruggero; Farhat, Jihane Ben; Van-Cutsem, Gilles; Cohen, Karen

    2017-09-29

    Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods. Cross-sectional population-based survey in KwaZulu-Natal, South Africa. Individuals 15-59 years were eligible. Interviews included questions about ARV use. Rapid HIV testing was performed at the participants' home. Blood specimens were collected for ARV detection, LAg-Avidity HIV incidence testing and viral load quantification in HIV-positive individuals. Multivariate logistic regression models were used to identify socio-demographic covariates associated with discordance between self-reported ART and ARV detection. Of the 5649 individuals surveyed, 1423 were HIV-positive. Median age was 34 years and 76.3% were women. ART coverage was estimated at 51.4% (95%CI:48.5-54.3), 53.1% (95%CI:50.2-55.9) and 56.1% (95%CI:53.5-58.8) using self-reported ART, ARV detection and both methods combined (classified as ART exposed if ARV detected and/or ART reported) respectively. ART coverage estimates using the 3 methods were fairly similar within sex and age categories except in individuals aged 15-19 years: 33.3% (95%CI:23.3-45.2), 33.8% (95%CI:23.9-45.4%) and 44.3% (95%CI:39.3-46.7) using self-reported ART, ARV detection and both methods combined. Viral suppression below 1000cp/mL in individuals on ART was estimated at 89.8% (95%CI:87.3-91.9), 93.1% (95%CI:91.0-94.8) and 88.7% (95%CI:86.2-90.7) using self-reported ART, ARV detection and both methods combined respectively. HIV incidence was estimated at 1.4 (95%CI:0.8-2.0) new cases/100 person-years when employing no measure of ARV use, 1.1/100PY (95%CI:0

  5. Reduced-complexity adaptive multi-channel assignment for shared access points in over-loaded small-cell networks

    KAUST Repository

    Radaydeh, Redha Mahmoud

    2013-06-01

    This paper proposes a reduced-complexity downlink multi-channel assignment scheme when feedback links are capacity-limited. The system model treats the case when multiple access points are allocated to serve scheduled users in over-loaded (i.e. dense) pico/femtocell networks. It assumes that the deployed access points can be shared simultaneously and employ isotropic antenna arrays of arbitrary sizes. Moreover, they transmit their data on a common physical channel and can not coordinate their transmissions. On the other hand, each scheduled user can be served by single transmit channel from each active access point at a time, and it lacks coordination with concurrent active users. The scheme operates according to the occupancy of available transmit channels, wherein extensively occupied access points are avoided adaptively, while reducing the load of processing. The operation is linked to a target performance via controlling the observed aggregate interference from the projected set of serving points. Through the analysis, results for the scheduled user outage performance, and the average number of active access points are presented. Numerical and simulations studies clarify the gains of the proposed scheme for different operating conditions. © 2013 IEEE.

  6. Asociación de LT-CD4 y carga viral con candidiasis bucal en pacientes VIH/SIDA en Talca, Chile Association between LT-CD4 and the viral load with oral candidiasis in HIV/AIDS patients in Talca, Chile

    Directory of Open Access Journals (Sweden)

    Pedro Brevis Azocar

    2009-12-01

    Full Text Available La candidiasis bucal aparece con frecuencia en las personas infectadas por el virus de la inmunodeficiencia humana (VIH y puede causar diversas manifestaciones clínicas y complicaciones. En los pacientes VIH la carga viral es considerada uno de los principales predictores en la progresión de la enfermedad. Se realizó un estudio en 29 pacientes adultos VIH-positivos para evaluar los niveles de linfocitos T-CD4 y carga viral; se estableció una relación con las manifestaciones de la candidiasis bucal. El análisis estadístico mostró que hubo relación entre la manifestación de la candidiasis bucal y la carga viral, pues en pacientes con cargas virales superiores a 10 000 copias/mL, las lesiones fueron más frecuentes.Oral candidiasis is frequently appearing in persons infected by human immunodeficiency virus (HIV and may to cause many clinical and complications manifestations. In HIV patients the viral load is considered one of the main predictors in disease progression. A study was conducted in 29 HIV-positive adult patients to assess the T-CD4 lymphocyte levels and the viral load establishing a relationship with oral candidiasis manifestations. The statistical analysis showed that there was a relationship between the oral candidiasis manifestation and the viral load since in patients with viral load higher than 10 000 copies/mL, lesions were more frequent.

  7. Relationship of Human Immunodeficiency Virus Viral Load in Cerebrospinal Fluid and Plasma in Patients Co-infected With Cryptococcal Meningitis.

    Science.gov (United States)

    Chang, Christina C; Kangethe, Richard; Omarjee, Saleha; Hiramen, Keshni; Gosnell, Bernadett; Sojane, Katlego; Moosa, Mohamed-Yunus S; Lewin, Sharon R; French, Martyn A; Ndung'u, Thumbi

    2017-01-01

    We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma samples in a prospective study of 91 HIV-infected, antiretroviral therapy-naive patients with cryptococcal meningitis. Cerebrospinal fluid HIV RNA was lower than in plasma (median 4.7 vs 5.2 log 10 copies/mL, P < .0001) and positively correlated with plasma HIV RNA, peripheral CD4 + T-cell percentage, and CSF CXCL10. Plasma/CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. Cerebrospinal fluid quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.

  8. Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle

    Science.gov (United States)

    Clausznitzer, Diana; Schulze, Manuel; Hüber, Christian M.; Lenz, Simon M.; Schlöder, Johannes P.; Trippler, Martin; Bartenschlager, Ralf; Lohmann, Volker; Kaderali, Lars

    2013-01-01

    Hepatitis C virus (HCV) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular HCV RNA replication. We therefore quantitatively measured viral RNA and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly validated the model using additional, independent experiments. Model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. A protective replication compartment proved to be essential for sustained RNA replication, balancing translation versus replication and thus effectively limiting RNA amplification. The model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to HCV replication. In gene expression profiling, we identified several key processes potentially determining cellular HCV replication efficiency. PMID:23990783

  9. Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.

    Directory of Open Access Journals (Sweden)

    Marco Binder

    Full Text Available Hepatitis C virus (HCV infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular HCV RNA replication. We therefore quantitatively measured viral RNA and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly validated the model using additional, independent experiments. Model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. A protective replication compartment proved to be essential for sustained RNA replication, balancing translation versus replication and thus effectively limiting RNA amplification. The model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to HCV replication. In gene expression profiling, we identified several key processes potentially determining cellular HCV replication efficiency.

  10. A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease.

    Science.gov (United States)

    Dahari, Harel; Layden-Almer, Jennifer E; Kallwitz, Eric; Ribeiro, Ruy M; Cotler, Scott J; Layden, Thomas J; Perelson, Alan S

    2009-04-01

    Patients with baseline hepatitis C virus-RNA levels (bHCV-RNA)>6 log IU/mL or cirrhosis have a reduced probability of a sustained-virologic response (SVR). We examined the relation between bHCV-RNA, cirrhosis, and SVR with a mathematical model that includes the critical-drug efficacy (epsilonc; the efficacy required for a drug to clear HCV), the infection-rate constant (beta), and the percentage of HCV-infected hepatocytes (pi). The relation between baseline factors and SVR was evaluated in 1000 in silico HCV-infected patients, generated by random assignment of realistic host and viral kinetic parameters. Model predictions were compared with clinical data from 170 noncirrhotic and 75 cirrhotic patients. The ranges chosen for beta and the viral production rate (p) resulted in bHCV-RNA levels that were in agreement with the distribution observed in US patients. With these beta and p values, higher bHCV-RNA levels led to higher epsilonc, resulting in lower SVR rates. However, higher beta values resulted in lower bHCV-RNA levels but higher pi and (epsilonc), predicting lower rates of SVR. Cirrhotic patients had lower bHCV-RNA levels than noncirrhotic patients (P=.013), and more had bHCV-RNA levels<6 log IU/mL (P<.001). Even cirrhotic patients with lower bHCV-RNA levels had lower SVR rates. An increase in beta could explain the results observed in cirrhotic patients. Our model predicts that higher bHCV-RNA levels lead to higher epsilonc, reducing the chance of achieving SVR; cirrhotic patients have lower SVR rates because of large pi values, caused by increased rates of hepatocyte infection.

  11. CCR5 Expression Is Reduced in Lymph Nodes of HIV Type 1–Infected Women, Compared With Men, But Does Not Mediate Sex-Based Differences in Viral Loads

    Science.gov (United States)

    Meditz, Amie L.; Folkvord, Joy M.; Lyle, Ngan H.; Searls, Kristina; Lie, Yolanda S.; Coakley, Eoin P.; McCarter, Martin; MaWhinney, Samantha; Connick, Elizabeth

    2014-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1)–infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences. Methods. CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1–infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA–producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used. Results. The percentage of CCR5+CD3+CD4+ cells was lower in women (mean, 12%) than men (mean, 16%; P = .034). Neither the percentage of CCR5+CD3+CD4+ cells nor the CCR5 density predicted viral load or HIV-1 RNA–producing lymph node cells (P ≥ .24), after adjusting for CD4+ T-cell count, race, and age. Women had marginally fewer HIV-1 RNA–producing cells (mean, 0.21 cells/mm2) than men (mean, 0.44 cells/mm2; P = .046). After adjusting for the frequency of HIV-1 RNA–producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P = .018). Conclusions. Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA–producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA–producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus. PMID:24179109

  12. Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

    Directory of Open Access Journals (Sweden)

    Brunna M. Alves

    2017-12-01

    Full Text Available Increased access to highly active antiretroviral therapy (HAART by human immunodeficiency virus postive (HIV+ individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23. Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

  13. Start point to savings - Better load demand analysis in commercial buildings

    Energy Technology Data Exchange (ETDEWEB)

    Abaravicius, Juozas; Pyrko, Jurek [Lund Univ., Dept of Energy Sciences (Sweden)

    2007-07-01

    Existing installations and energy systems in most commercial buildings could be used in a more efficient way to provide savings - both in terms of energy and load demand. The key for effective operation is a thorough and detailed analysis of energy use patterns that creates essential baseline for energy savings and the development of demand response (DR) strategies. The knowledge of energy demand variations is still very limited and the use of methods to analyse the load demand is rare. Many utilities have recently installed interval (hourly) metering even for smaller commercial users and households. This is a big step forward; however, experience shows that the data is being used only to a limited extent, mostly for billing purposes only. This paper reports about a study conducted with the objective of developing a detailed load demand analysis for commercial buildings. The study results should provide essential information for the formation and evaluation of future DR and energy efficiency strategies. This study was performed in collaboration with IKEA and E.ON and contributes to an ongoing IKEA energy efficiency programme. Two sample department stores in Sweden were selected and analysed within this project. The demand data analysis covers almost 3 years period, 2004-2006.This study contributes to new knowledge of energy use patterns (load demand) in commercial buildings. It proposes solutions of load-related problems, evaluates energy and load savings potential, identifies and analyses the needs, motives and barriers for participation in DR programmes. The study provides recommendations for ongoing and future efficiency and DR strategies and discusses the potential economic benefits from the DR measures.

  14. A Central Swivel Point in the RFC Clamp Loader Controls PCNA Opening and Loading on DNA

    OpenAIRE

    Sakato, Miho; O’Donnell, Mike; Hingorani, Manju M.

    2011-01-01

    Replication Factor C (RFC) is a 5-subunit complex that loads PCNA clamps onto primer-template DNA (ptDNA) during replication. RFC subunits belong to the AAA+ superfamily, and their ATPase activity drives interactions between the clamp loader, clamp, and ptDNA, leading to topologically linked PCNA•ptDNA. We report the kinetics of transient events in S. cerevisiae RFC catalyzed PCNA loading, including ATP-induced RFC activation, PCNA opening, ptDNA binding, ATP hydrolysis, PCNA closing and PCNA...

  15. Determination of HPV DNA viral load by hybrid capture assay and its association with cytological findings Determinação da carga viral de DNA de HPV pelo ensaio de captura híbrida e sua associação com achados citológicos

    Directory of Open Access Journals (Sweden)

    Inês Aparecida Tozetti

    2006-12-01

    Full Text Available OBJECTIVE: To compare the relation between HPV viral load by hybrid capture II test (HCII and cytological findings. METHODS: Three hundred sixty-two reagent samples to HPV DNA by HCII had their viral loads classified in four categories and correlated to cytological results. RESULTS: Twenty-two samples (6.1% were reagent only to low-risk oncogenic types (group A and 340 (93.9% were reagent to high-risk oncogenic types (group B. The correlation between viral load for the reagent samples to group A and cytological results showed low-grade squamous intraepithelial lesion (LSIL predominance (50%. Most of this group samples had viral load between 1 to OBJETIVO: Comparar a relação entre a carga viral do HPV por captura híbrida II (HCII e os achados citológicos. METODOS: Trezentas e sessenta e duas amostras reagentes para DNA de HPV por HCII tiveram suas cargas virais classificadas em quatro categorias e correlacionadas aos resultados citológicos. RESULTADOS: Vinte e duas amostras (6,1% foram reagentes somente para os tipos de baixo risco oncogênico (grupo A e 340 (93,9% foram reagentes para os tipos de alto risco oncogênico (grupo B. A correlação entre carga viral das amostras reagentes para o grupo A e resultados citológicos mostrou predominância (50% de lesão escamosa intraepitelial de baixo grau (LSIL. A maioria das amostras desse grupo teve carga viral entre 1 e < 10RLU/PCA. Nos pacientes reagentes para o grupo B observamos que 52,1% tiveram citologia LSIL e 38,2% tiveram citologia negativa para lesão intraepitelial e malignidade (NILM. Os pacientes com LSIL tiveram a carga viral bem distribuída, com ligeira predominância da categoria de 100 a < 1.000RLU/PCB. As amostras com carga viral entre 1 e < 10RLU/PCB mostraram predominância de citologia NILM (48.1%. Lesões escamosas de alto grau (3,4% foram presentes nas amostras com carga viral entre 100 e < 1.000RLU/PCB (p = 0,023. Houve correlação entre a mediana da carga viral para o

  16. Operating and Loading Conditions of a Three-Level Neutral-Point-Clamped Wind Power Converter Under Various Grid Faults

    DEFF Research Database (Denmark)

    Ma, Ke; Liserre, Marco; Blaabjerg, Frede

    2014-01-01

    In order to fulfill the growing demands from the grid side, full-scale power converters are becoming popular in the wind turbine system. The low-voltage ride-through (LVRT) requirements may not only cause control problems but also result in overstressed components for the power converter. However...... are analytically solved and simulated. It has been found that the operating and loading conditions of the converter under LVRT strongly depend on the types/severity values of grid voltage dips and also the chosen control algorithms. The thermal distribution among the three phases of the converter may be quite......, the thermal loading of the wind power converter under various grid faults is still not yet clarified, particularly at megawatt power level. In this paper, the impacts by three types of grid faults to a three-level neutral-point-clamped (3L-NPC) wind power converter in terms of operating and loading conditions...

  17. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

    Directory of Open Access Journals (Sweden)

    Pascale Ondoa

    Full Text Available Genital viral load (GVL is the main determinant of sexual transmission of human immune-deficiency virus (HIV. The effect of antiretroviral therapy (ART on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.All participants were evaluated for GVL, plasma viral load (PVL, CD4 count, various sexually-transmitted infections (STIs at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15 and at month 12 with MIP-1β (95% CI 0.96-21.32 after controlling for baseline GVL, PVL and month 12 IL-8.Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

  18. Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent Enhancement in Dengue-Primed Zika Virus-Infected Patients.

    Science.gov (United States)

    Terzian, Ana Carolina Bernardes; Schanoski, Alessandra Soares; Mota, Mânlio Tasso de Oliveira; da Silva, Rafael Alves; Estofolete, Cássia Fernanda; Colombo, Tatiana Elias; Rahal, Paula; Hanley, Kathryn A; Vasilakis, Nikos; Kalil, Jorge; Nogueira, Maurício Lacerda

    2017-10-15

    The pathogenesis of severe dengue disease involves immune components as biomarkers. The mechanism by which some dengue virus (DENV)-infected individuals progress to severe disease is poorly understood. Most studies on the pathogenesis of severe dengue disease focus on the process of antibody-dependent enhancement (ADE) as a primary risk factor. With the circulation of Zika virus (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to DENV. The influence of such exposure on Zika disease outcomes remains unknown. We investigated whether patients previously exposed to DENV exhibited higher viremia when exposed to a subsequent, heterologous dengue or Zika infection than those patients not previously exposed to dengue. We measured viral loads and cytokine profile during patients' acute infections. Neither dengue nor Zika viremia was higher in patients with prior DENV infection, although the power to detect such a difference was only adequate in the ZIKV analysis. Of the 10 cytokines measured, only 1 significant difference was detected: Levels of interleukin 1β (IL-1β) were lower in dengue-infected patients who had experienced a previous dengue infection than patients infected with dengue for the first time. However, power to detect differences between groups was low. In Zika-infected patients, levels of IL-1β showed a significant, positive correlation with viral load. No signs of ADE were observed in vivo in patients with acute ZIKV infection who had prior exposure to DENV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Novel use of surveillance data to detect HIV-infected persons with sustained high viral load and durable virologic suppression in New York City.

    Directory of Open Access Journals (Sweden)

    Arpi S Terzian

    Full Text Available Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL.Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average.Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.

  20. Effects of antioxidants on CD4 and viral load in HIV-infected women in sub-Saharan Africa - dietary supplements vs. local diet.

    Science.gov (United States)

    Nkengfack, Germaine N; Torimiro, Judith N; Englert, Heike

    2012-02-01

    In sub-Sahara Africa, micronutrient deficiency, especially of antioxidant micronutrients including vitamins A, C, and E, beta-carotene, selenium, zinc, and polyphenols is very common in HIV-positive patients. Amongst adults, women are the most vulnerable. Antioxidants are known to play a vital role in the immune system, reducing oxidative stress. Oxidative stress is induced by excess production of reactive oxygen species (ROS), due to the HIV infection. Such damage may be prevented or moderated through adequate oral intake of antioxidants, scavenging ROS, as well as protecting cells and tissues against oxidative stress. Antioxidants can be provided to the body through locally available antioxidant rich-diets such as fruit-and-vegetable-based diets and/or dietary supplements. Provision of antioxidants through local diets or dietary supplements exercise beneficial effects on biological markers of the immune system (CD4 and viral load). However, while dietary supplements represent a costly and short-term strategy to limiting antioxidant deficiency, local diets, combined with adequate nutritional education, can provide a low-cost and long-term strategy to reduce oxidative stress, prevent micronutrient deficiency, and slow down HIV disease progression. The former can be applicable in countries around the West, Central, and South coast of Africa, which are rich in natural food resources. In contrast with significant evidence that dietary supplements confer benefits in HIV patients, fewer data are available relating to the benefits of local diets. Thus the need to do more research in this area arises. This review compares available data on effects of antioxidants on CD4 and viral load in HIV-positive women noneligible for antiretroviral therapy. Intake of antioxidants though dietary supplements and local diet, associated with nutritional education, is compared. Studies conducted in sub-Sahara Africa are considered.

  1. [Quality of life of people living with HIV/AIDS and its relationship with CD4+ lymphocytes, viral load and time of diagnosis].

    Science.gov (United States)

    Ferreira, Brunno Elias; Oliveira, Isabele Mendes; Paniago, Anamaria Mello Miranda

    2012-03-01

    Quality of life (QOL) has accompanied the treatment of AIDS patients, along with pharmacological innovations that have allowed patients to live longer and maintain their well-being. The present study aimed at evaluating the QOL of these patients and correlate it with clinical and laboratory data. The study included 205 patients with HIV/AIDS, who answered the WHOQOL-120-HIV; and whose socio-demographic data, clinical and laboratory findings were collected. The average age was 40.59 ± 11.81 years; CD4+ lymphocyte count, 397.9 ± 232.84 mm³; and years of diagnosis of HIV, 5.23 ± 3.94. Viral load was relationships (13.7 ± 2.2), physical (12.7 ± 3.5), independence (12.6 ± 2.5), personal beliefs (12.4 ± 2.4), and environment (12.4 ± 1.8). The best scores on pain, pleasure, social support, physical environment, and personal belief facets were observed for those with higher CD4 levels (p finance, leisure, concerns about the future, overall QOL, and perceived health facets were observed for patients with viral load <50 (p < 0.05). The highest rates for energy, fatigue, sexual activity, information, transportation, symptoms, care, and concerns about the future facets were seen in patients with less time of diagnosis (p < 0.05). HIV/AIDS patients in the study had an intermediate QOL correlating to CD4 levels, VL, and time of diagnosis.

  2. Prevalence and risk factors associated to chronic kidney disease in HIV-infected patients on HAART and undetectable viral load in Brazil.

    Directory of Open Access Journals (Sweden)

    Andréia M Menezes

    Full Text Available BACKGROUND: To determine the prevalence and associated factors with chronic kidney disease (CKD in a cohort of HIV-positive individuals with undetectable viral load on HAART. METHODS: From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm(3, and CD4 ≥ 200 cells/mm(3, were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m(2, for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD. RESULTS: CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84-8.16, time on HAART (RR = 1.15, 95%CI,1.03-1.27 and tenofovir exposure (RR = 2.25, 95%CI, 1.04-4.95. Higher weight (RR = 0.88 95%CI, 0.82-0.96 was associated to normal function. CONCLUSIONS: CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.

  3. Design of sampling locations for river water quality monitoring considering seasonal variation of point and diffuse pollution loads.

    Science.gov (United States)

    Varekar, Vikas; Karmakar, Subhankar; Jha, Ramakar; Ghosh, N C

    2015-06-01

    The design of a water quality monitoring network (WQMN) is a complicated decision-making process because each sampling involves high installation, operational, and maintenance costs. Therefore, data with the highest information content should be collected. The effect of seasonal variation in point and diffuse pollution loadings on river water quality may have a significant impact on the optimal selection of sampling locations, but this possible effect has never been addressed in the evaluation and design of monitoring networks. The present study proposes a systematic approach for siting an optimal number and location of river water quality sampling stations based on seasonal or monsoonal variations in both point and diffuse pollution loadings. The proposed approach conceptualizes water quality monitoring as a two-stage process; the first stage of which is to consider all potential water quality sampling sites, selected based on the existing guidelines or frameworks, and the locations of both point and diffuse pollution sources. The monitoring at all sampling sites thus identified should be continued for an adequate period of time to account for the effect of the monsoon season. In the second stage, the monitoring network is then designed separately for monsoon and non-monsoon periods by optimizing the number and locations of sampling sites, using a modified Sanders approach. The impacts of human interventions on the design of the sampling net are quantified geospatially by estimating diffuse pollution loads and verified with land use map. To demonstrate the proposed methodology, the Kali River basin in the western Uttar Pradesh state of India was selected as a study area. The final design suggests consequential pre- and post-monsoonal changes in the location and priority of water quality monitoring stations based on the seasonal variation of point and diffuse pollution loadings.

  4. Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

    Science.gov (United States)

    Galizzi, Nadia; Galli, Laura; Poli, Andrea; Gianotti, Nicola; Carini, Elisabetta; Bigoloni, Alba; Tambussi, Giuseppe; Nozza, Silvia; Lazzarin, Adriano; Castagna, Antonella; Mancusi, Daniela; Termini, Roberta

    2018-01-01

    A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNAplus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters. In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other

  5. HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype

    Directory of Open Access Journals (Sweden)

    Tuane Carolina Ferreira Moura

    2017-01-01

    Full Text Available The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A, rs1800451 (MBL ⁎C, G>A, and rs5030737 (MBL ⁎D, C>T polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n=65, hepatitis C virus (HCV; n=92, and a noninfected control group (n=300 were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

  6. Determinants of spontaneous surface antigen loss in hepatitis B e antigen-negative patients with a low viral load.

    Science.gov (United States)

    Tseng, Tai-Chung; Liu, Chun-Jen; Yang, Hung-Chih; Su, Tung-Hung; Wang, Chia-Chi; Chen, Chi-Ling; Kuo, Stephanie Fang-Tzu; Liu, Chen-Hua; Chen, Pei-Jer; Chen, Ding-Shinn; Kao, Jia-Horng

    2012-01-01

    Loss of hepatitis B surface antigen (HBsAg) usually indicates the cure of hepatitis B virus (HBV) infection. In spontaneous hepatitis B e antigen (HBeAg) seroconverters, lower serum HBsAg and HBV DNA levels have been shown to be associated with HBsAg loss over time. However, little is known about their impacts on HBsAg loss in HBeAg-negative patients with limited viral replication. A total of 688 HBeAg-negative patients with baseline serum HBV DNA levels loss were investigated. In a mean follow-up of 11.6 years, the average annual rate of HBsAg loss was 1.6%. Baseline HBsAg and HBV DNA levels were inversely associated with subsequent HBsAg loss. When compared to patients who had HBsAg levels >1000 IU/mL, the rates of HBsAg loss were significantly higher in patients with HBsAg levels of 100-999, 10-99, and loss was 13.2 (95% CI, 7.8-22.1) for HBsAg level loss. In HBeAg-negative patients with HBV genotype B or C infection who have HBV DNA level loss. Copyright © 2011 American Association for the Study of Liver Diseases.

  7. Interleukin-28B polymorphisms are associated with hepatitis C virus clearance and viral load in a HIV-1-infected cohort

    DEFF Research Database (Denmark)

    Clausen, L N; Weis, N; Astvad, K

    2011-01-01

    Summary. Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP) of the i......Summary. Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP......) of the interferon-¿3 coding interleukin (IL)-28B gene to study the relationship between IL28B SNPs and outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed chronic infection. The exonic rs8103142 CT...... higher median HCV RNA levels than individuals with unfavourable haplotype blocks (P = 0.05). Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence...

  8. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Astvad, Karen; Ladelund, Steen

    2012-01-01

    risk [adjusted mortality rate ratio (aMRR): 1.30 (1.10,1.54)] when adjusted for sex, age, HIV exposure group, CD4 cell count, HIV RNA, HCV genotype and interleukin (IL)-28B genotype. Further, HCV genotype 3 vs. 1 [aMRR: 1.83 (1.12, 2.98)] and HIV RNA [aMRR: 3.14 (1.37,7.17) for undetectable vs. just......OBJECTIVE: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis......) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have...

  9. In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine.

    Science.gov (United States)

    Ma, Jian; Jiang, Chenggang; Lin, Yuezhi; Wang, Xuefeng; Zhao, Liping; Xiang, Wenhua; Shao, Yiming; Shen, Rongxian; Kong, Xiangang; Zhou, Jianhua

    2009-01-01

    To study the in vivo evolution of the attenuated Chinese equine infectious anemia virus (EIAV) vaccine, viral gp90 gene variation and virus replication in immunosuppressed hosts were investigated. The results showed that after vaccination, the gp90 gene followed an evolutionary trend of declining diversity. The trend coincided with the maturation of immunity to EIAV, and eventually, the gp90 gene became highly homologous. The sequences of these predominant quasispecies were consistently detected up to 18 months after vaccination. Furthermore, after transient immune suppression with dexamethasone, the plasma viral RNA copy number of the vaccine strain in three vaccinated ponies remained consistently below the "pathogenic threshold" level, while the viral load increased by 25,000-fold in the positive control of an inapparent carrier of the parental virulent strain. This study is the first to provide evidence for the safety of an attenuated lentiviral vaccine with decreased genomic diversity and consistently low viral replication under suppressed immunity.

  10. Variation in the location of the shoe sole flexion point influences plantar loading patterns during gait

    NARCIS (Netherlands)

    van der Zwaard, B.C.; Vanwanseele, B.; Holtkamp, F.; van der Horst, H.E.; Elders, P.J.M.; Menz, H.B.

    2014-01-01

    Background: Several footwear design characteristics are known to have detrimental effects on the foot. However, one characteristic that has received relatively little attention is the point where the sole flexes in the sagittal plane. Several footwear assessment forms assume that this should ideally

  11. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens.

    Science.gov (United States)

    Susta, Leonardo; Diel, Diego G; Courtney, Sean; Cardenas-Garcia, Stivalis; Sundick, Roy S; Miller, Patti J; Brown, Corrie C; Afonso, Claudio L

    2015-08-08

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (NK), cytotoxic T lymphocytes and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such it might have the potential to affect replication and pathogenesis of Newcastle disease virus (NDV). To assess the effect of IL-2 during NDV infection in chickens, we produced a recombinant virulent NDV strain expressing chicken IL-2 (rZJ1-IL2). The effects of IL-2 expression were investigated in vivo using the intracerebral pathogenicity index (ICPI) in day-old chicks and pathogenesis experiments in 4-week-old chickens. In these studies, rZJ1-IL2 was compared to a control virus expressing the green fluorescent protein (rZJ1-GFP). Assessed parameters included survival curves, detailed histological and immunohistochemical grading of lesions in multiple organs, and virus isolation in blood, spleen and mucosal secretions of infected birds. At the site of infection (eyelid), expression of IL-2 was demonstrated in areas of rZJ-IL2 replication, confirming IL-2 production in vivo. Compared to rZJ1-GFP strain, rZJ1-IL2 caused milder lesions and displayed decreased viral load in blood, spleen and mucosal secretions of infected birds. In the rZJ1-IL2-infected group, virus level in the blood peaked at day 4 post-infection (pi) (10(3.46) EID50 /0.1 ml) and drastically decreased at day 5 pi (10(0.9) EID50/0.1 ml), while in the rZJ1-GFP-infected group virus levels in the blood reached 10(5.35) EID50/0.1 ml at day 5. However, rZJ1-IL2-infected groups presented survival curves similar to control birds infected with rZJ1-GFP, with comparable clinical signs and 100 % mortality. Further, expression of IL-2 did not significantly affect the ICPI scores, compared to rZJ1-GFP strain. Increased

  12. Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa.

    Science.gov (United States)

    Joseph Davey, D; Abrahams, Z; Feinberg, M; Prins, M; Serrao, C; Medeossi, B; Darkoh, E

    2018-05-01

    Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.

  13. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial.

    Science.gov (United States)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W

    2017-08-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4

  14. Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4+ Level

    Science.gov (United States)

    de Freitas, Vera Lúcia Teixeira; da Silva, Sheila Cristina Vicente; Sartori, Ana Marli; Bezerra, Rita Cristina; Westphalen, Elizabeth Visone Nunes; Molina, Tatiane Decaris; Teixeira, Antonio R. L.; Ibrahim, Karim Yaqub; Shikanai-Yasuda, Maria Aparecida

    2011-01-01

    Background Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4+ cells or the CD4+/CD8+ ratio. Conclusions qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4+ cells/mm3 and the CD4+/CD8+ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy. PMID

  15. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  16. Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard.

    Science.gov (United States)

    Semenova, Touyana; Lupo, Julien; Alain, Sophie; Perrin-Confort, Gwladys; Grossi, Laurence; Dimier, Julie; Epaulard, Olivier; Morand, Patrice; Germi, Raphaële

    2016-07-01

    The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Dynamic Interaction of Interfacial Point Source Loading and Cylinder in an Elastic Quarter with Anti-plane Shear

    Science.gov (United States)

    Chun, Gao; Hui, Qi; Nan, Pan Xiang; Bo, Zhao Yuan

    2017-07-01

    Theoretical steady state solution of a semi-circular cylinder impacted by an anti-plane point loading in a vertical bound of an elastic quarter is formulated in this paper through using image method and wave function expansion series. The elastic quarter is extended as a half space, and the semi-circular interfacial cylinder is extended as a circular cylinder. Displacement field is constructed as series of Fourier-Hankel and Fourier-Bessel wave functions. At last, circular boundary is expanded as Fourier series to determine coefficients of wave function. Numerical results show that material parameters have two widely divergent effects on the radial and circumferential dynamic stress distribution.

  18. [Spatial discharge characteristics and total load control of non-point source pollutants based on the catchment scale].

    Science.gov (United States)

    Wang, Xia-Hui; Lu, Jun; Zhang, Qing-Zhong; Wang, Bo; Yao, Rui-Hua; Zhang, Hui-Yuan; Huang, Feng

    2011-09-01

    Agricultural non-point source pollution is one of the major causes of water quality deterioration. Based on the analysis of the spatial discharge characteristics and intensity of major pollutants from the agricultural pollution source, the establishment of spatial management subzones for controlling agricultural non-point pollution and a design of a plan for total load control of pollutants from each subzone is an important way to improve the efficiency of control measures. In this paper the Four Lake basin in Hubei Province is adopted as the research case region and a systematic research of the control countermeasures of agricultural non-point pollution based on the catchment scale is carried out. The results shows that in the Four Lake basin, the COD, total nitrogen, total phosphorus and ammonia nitrogen load of the water environment are mainly caused by agricultural non-point pollution. These four kinds of non-point source pollutants respectively account for 67.6%, 82.2%, 84.7% and 50.9% of the total pollutant discharge amount in the basin. The analysis of the spatial discharge characteristics of non-point source pollutants in the Four Lake basin shows that the major contributor source regions of non-point source pollutant in the basin are the four counties, including Honghu, Jianli, Qianjiang and Shayang where the aquatic and livestock production are relatively developed. According to the spatial discharge characteristics of the pollutants and the evaluation of the discharge intensity of pollutants, the Four Lake basin is divided into three agricultural non-point pollution management subzones, which including Changhu upstream aquatic and livestock production pollution control subzone, Four-lake trunk canal rural non-point source pollution control subzone and Honghu aquatic production pollution control subzone. Specific pollution control measures are put forward for each subzone. With a comprehensive consideration of the water quality amelioration and the

  19. Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young Men Who Have Sex with Men and Transgender Women in Chicago: Implications for Epidemiology, Care, and Prevention.

    Science.gov (United States)

    Mustanski, Brian; Ryan, Daniel T; Remble, Thomas A; D'Aquila, Richard T; Newcomb, Michael E; Morgan, Ethan

    2018-04-10

    Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (< 200 copies/mL) via study-specific laboratory testing. Concordance between self-report and medical record VL values was 80% and between self-report and study-specific laboratory testing was 73%; 34% of participants with a detectable study-specific VL self-reported an undetectable VL at last medical visit, and another 28% reported not knowing their VL status. Periods of lapsed viral suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.

  20. Correlation between LTR point mutations and proviral load levels among Human T cell Lymphotropic Virus type 1 (HTLV-1 asymptomatic carriers

    Directory of Open Access Journals (Sweden)

    Neto Walter K

    2011-12-01

    Full Text Available Abstract Background In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE of the genuine human T-cell leukemia virus type I (HTLV-1 viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1i nfected cells and alter the proviral load (PvL. To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. Methods A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. Results Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31, 27.5% (8/29, and 61.8% (21/34 of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p p > 0.05. This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p p > 0. 05. Conclusions The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.

  1. Correlation between LTR point mutations and proviral load levels among human T cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers.

    Science.gov (United States)

    Neto, Walter K; Da-Costa, Antonio C; de Oliveira, Ana Carolina S; Martinez, Vanessa P; Nukui, Youko; Sabino, Ester C; Sanabani, Sabri S

    2011-12-13

    In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1-infected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p 0. 05). The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.

  2. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

  3. A retrospective analysis of AIDS-associated Kaposi's sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells/mm(3).

    Science.gov (United States)

    Mani, Deepthi; Neil, Nancy; Israel, Rebecca; Aboulafia, David M

    2009-01-01

    To compare the clinical course of patients with AIDS-related Kaposi's sarcoma (KS) with CD4 counts >300 cells/mm(3) and undetectable HIV viral loads (VLs) to patients with AIDS-KS with lesser CD4 counts and detectable HIV VLs. We retrospectively analyzed a cohort of 91 patients with AIDS-KS in a multispeciality clinic. We used chi(2) and Student t tests to analyze intragroup differences; survival was determined by Kaplan-Meier analysis. Twenty (22%) of the 91 patients had newly diagnosed, persistent or progressive KS despite CD4 counts >300 cells/mm(3) and undetectable HIV VLs. Age, gender, ethnicity, mode and duration of HIV acquisition, type of antiretroviral therapy (ART), and KS therapy did not differ significantly (P counts active antiretroviral (HAART) era, a substantial proportion of patients with KS had undetectable HIV VLs and CD4 counts greater than the level typically associated with opportunistic diseases. They required systemic therapy to control their KS but were significantly less likely to die and demonstrated a trend toward better 15-year survival than patients having KS with lesser CD4 counts and detectable HIV VLs.

  4. Association of Adolescent- and Caregiver-Reported Antiretroviral Therapy Adherence with HIV Viral Load Among Perinatally-infected South African Adolescents.

    Science.gov (United States)

    Brittain, Kirsty; Asafu-Agyei, Nana Akua; Hoare, Jacqueline; Bekker, Linda-Gail; Rabie, Helena; Nuttall, James; Roux, Paul; Stein, Dan J; Zar, Heather J; Myer, Landon

    2018-03-01

    Accurate measurement of antiretroviral therapy (ART) adherence remains challenging and there are few data assessing the validity of self-reported adherence among perinatally HIV-infected adolescents. We examined adolescent and caregiver reports of adolescent adherence among perinatally-infected adolescents aged 9-14 years in Cape Town, South Africa, and explored factors that may modify associations between reported adherence and elevated viral load (VL). Among 474 adolescents (median age 12.0 years; median duration of ART use 7.5 years), elevated VL and caregiver- and adolescent-report of missed ART doses were common. Elevated VL was particularly prevalent among older, male adolescents. Low-moderate concordance was observed between caregiver and adolescent report. Among adolescents aged ≥ 12 years, caregiver- and adolescent-reported adherence was associated with elevated VL across most items assessed, but few significant associations were observed among adolescents adolescents who require adherence interventions are needed in this context.

  5. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials.

    Science.gov (United States)

    Simoni, Jane M; Pearson, Cynthia R; Pantalone, David W; Marks, Gary; Crepaz, Nicole

    2006-12-01

    Adherence to highly active antiretroviral therapy (HAART) is generally suboptimal, limiting the effectiveness of HAART. This meta-analytic review examined whether behavioral interventions addressing HAART adherence are successful in increasing the likelihood of a patient attaining 95% adherence or an undetectable HIV-1 RNA viral load (VL). We searched electronic databases from January 1996 to September 2005, consulted with experts in the field, and hand searched reference sections from relevant articles. Nineteen studies (with a total of 1839 participants) met the selection criteria of describing a randomized controlled trial among adults evaluating a behavioral intervention with HAART adherence or VL as an outcome. Random-effects models indicated that across studies, participants in the intervention arm were more likely than those in the control arm to achieve 95% adherence (odds ratio [OR] = 1.50, 95% confidence interval [CI]: 1.16 to 1.94); the effect was nearly significant for undetectable VL (OR = 1.25; 95% CI: 0.99 to 1.59). The intervention effect for 95% adherence was significantly stronger in studies that used recall periods of 2 weeks or 1 month (vs.

  6. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew

    2002-01-01

    SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified...... as responders (ITT/s=f); and 2) patients with a pVL below a given cut-off at week 48 whether they remained on initial assigned therapy or switched therapy were responders (ITT/s incl). In both analyses, patients with missing data at week 48 were classified as failures (i.e., non-responders). RESULTS: According....../s=f, and 41-72% according to ITT/s incl. Among those who discontinued the therapy to be evaluated in these two trials, 13-45% (cohort: 39-74%) subsequently experienced a virological response at week 48. The subsequent response rates were associated with the reason for discontinuation (toxicity versus...

  7. HIV infection, viral load, low birth weight, and nevirapine are independent influences on growth velocity in HIV-exposed South African infants.

    Science.gov (United States)

    Ramokolo, Vundli; Lombard, Carl; Fadnes, Lars T; Doherty, Tanya; Jackson, Debra J; Goga, Ameena E; Chhagan, Meera; Van den Broeck, Jan

    2014-01-01

    Data from a prospective multisite cohort study were used to examine the effect of HIV exposure, untreated HIV infection, and single-dose nevirapine on infant growth velocity. The 2009 WHO growth velocity standards constitute a new tool for this type of investigation and are in need of functional validation. In period 1 (3-24 wk), 65 HIV-infected, 502 HIV-exposed uninfected (HEU), and 216 HIV-unexposed infants were included. In period 2 (25-36 wk), 31 infants moved from the HEU group to the HIV-infected group. We compared weight velocity Z-scores (WVZ) and length velocity Z-scores (LVZ) by HIV group and assessed their independent influences. In period 1, mean WVZ (95% CI) was significantly (P infected [-0.87 (-1.77, 0.04)] than HEU [0.81 (0.67, 0.94)] and unexposed [0.55 (0.33, 0.78)] infants. LVZ showed similar associations. In both periods, sick infants and those exposed to higher maternal viral loads had lower WVZ. Higher mean LVZ was associated with low birth weight. Infants that had received nevirapine had higher LVZ. In conclusion, HIV infection and not exposure was associated with low WVZ and LVZ in period 1. Eliminating infant HIV infection is a critical component in averting HIV-related poor growth patterns in infants in the first 6 mo of life.

  8. Changes in leukocyte subsets of pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome.

    Science.gov (United States)

    Ladinig, Andrea; Gerner, Wilhelm; Saalmüller, Armin; Lunney, Joan K; Ashley, Carolyn; Harding, John C S

    2014-12-14

    In spite of more than two decades of extensive research, the understanding of porcine reproductive and respiratory syndrome virus (PRRSv) immunity is still incomplete. A PRRSv infection of the late term pregnant female can result in abortions, early farrowings, fetal death, and the birth of weak, congenitally infected piglets. The objectives of the present study were to investigate changes in peripheral blood mononuclear cell populations in third trimester pregnant females infected with type 2 PRRSv (NVSL 97-7895) and to analyze potential relationships with viral load and fetal mortality rate. PRRSv infection caused a massive, acute drop in total leukocyte counts affecting all PBMC populations by two days post infection. Except for B cells, cell counts started to rebound by day six post infection. Our data also show a greater decrease of naïve B cells, T-helper cells and cytolytic T cells than their respective effector or memory counterparts. Absolute numbers of T cells and γδ T cells were negatively associated with PRRSv RNA concentration in gilt serum over time. Additionally, absolute numbers of T helper cells may be predictive of fetal mortality rate. The preceding three leukocyte populations may therefore be predictive of PRRSv-related pathological outcomes in pregnant gilts. Although many questions regarding the immune responses remain unanswered, these findings provide insight and clues that may help reduce the impact of PRRSv in pregnant gilts.

  9. CD4 and viral load dynamics in antiretroviral-naive HIV-infected adults from Soweto, South Africa: a prospective cohort.

    Directory of Open Access Journals (Sweden)

    Neil A Martinson

    Full Text Available BACKGROUND: CD4 count is a proxy for the extent of immune deficiency and declines in CD4 count are a measure of disease progression. Decline in CD4 count is an important component: for estimating benefits of ARV treatment; for individual level counselling on the rapidity of untreated disease progression and prognosis; and can be used in planning demand for health services. Our objective is to report CD4 decline and changes in viral load (VL in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates. METHODS: HIV-infected, tuberculin skin test positive adults who were not eligible for antiretroviral (ARV treatment were randomized to a trial of preventive treatment from 2003-2005. VL and CD4 count were assessed at enrollment and CD4 counts repeated at least annually. During follow-up, individuals whose CD4 counts decreased to 100,000 (N = 122 copies/ml. CONCLUSIONS: Our data suggests that six and a half years will elapse for an individual's CD4 count to decline from 750 to 350 cells/mm3 in the absence of ART.

  10. Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+T lymphocyte count and detection of EBV, CMV and HSV Co-infecção viral na cavidade bucal de crianças infectadas pelo HIV: relação entre carga viral, contagem de linfócitos T-CD4+ e detecção de EBV, CMV e HSV

    Directory of Open Access Journals (Sweden)

    Liliane Janete Grando

    2005-09-01

    Full Text Available Viral coinfection in the oral cavity associated to HIV infection was evaluated in 180 children from birth to 13 years of age of both sexes. The oral examinations were performed at the Pediatric AIDS Outpatient Clinic, São Lucas Hospital and Clinic Hospital, both in Porto Alegre, Brazil and at the School of Dental Medicine, University Hospital Center, State University of New York at Stony Brook, USA. The aim of this study was to identify the presence of viral infections in the oral cavity. PCR technique was used to determine opportunistic viral infections caused by CMV, EBV, and HSV in mucosal swabs. A high frequency of viral infection was detected in the oral cavity of HIV-infected children determined by the PCR technique. HIV-infected children with viruses had a favorable CD4+T lymphocyte count and unfavorable viral load.A relação entre a infecção pelo HIV e a presença de diferentes tipos de vírus na cavidade bucal foi estudada em 180 crianças HIV-positivo, com idades entre zero e 13 anos de idade, de ambos os sexos. Os exames foram realizados nos Ambulatórios de Aids Pediátrica dos Hospitais São Lucas e de Clínicas, ambos em Porto Alegre, RS, Brasil e no Centro Hospitalar Universitário da Universidade Estadual de Nova Iorque, em Stony Brook (EUA. O objetivo desta pesquisa foi usar a técnica da PCR para detectar a presença dos vírus CMV, EBV e HSV na cavidade bucal desses pacientes, independentemente da presença ou não de manifestações estomatológicas relacionadas aos mesmos. Pode-se concluir que foi alta a freqüência de vírus detectados na cavidade bucal das crianças da amostra através da técnica da PCR e que a contagem média de linfócitos T-CD4+ das crianças com a presença dos vírus encontrava-se próxima da normalidade, enquanto a Carga Viral do HIV encontrava-se elevada.

  11. Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1 Evaluation of a molecular assay for determining viral load on HIV-1 antibody negative patients

    Directory of Open Access Journals (Sweden)

    José Moreira Pereira

    2002-01-01

    Full Text Available O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika foi repetidamente positiva na ausência de anticorpos para HIV e chama atenção para o fato de que a carga viral abaixo de 10 mil cópias/ml é de difícil interpretação, como tem sido assinalado em numerosos artigos, em que foram utilizadas outras metodologias.The plasma viral load test for HIV-1,a exquisitely high sensitive assay, were neither developed nor evaluated for the diagnosis of primary HIV infection; therefore, their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. This article reported four cases of false positive results obtained by using NucliSens viral load assay (Organon Teknika and emphasize the importance that low positive plasma viral load (< 10 000 copies/ml may be difficult to interpret how has been assinalated in numerous articles in the medical literature, using other methodologies.

  12. Reported Church Attendance at the Time of Entry into HIV Care is Associated with Viral Load Suppression at 12 Months.

    Science.gov (United States)

    Van Wagoner, Nicholas; Elopre, Latesha; Westfall, Andrew O; Mugavero, Michael J; Turan, Janet; Hook, Edward W

    2016-08-01

    The Southeast has high rates of church attendance and HIV infection rates. We evaluated the relationship between church attendance and HIV viremia in a Southeastern US, HIV-infected cohort. Viremia (viral load ≥200 copies/ml) was analyzed 12 months after initiation of care. Univariate and multivariable logistic regression models were fit for variables potentially related to viremia. Of 382 patients, 74 % were virally suppressed at 12 months. Protective variables included church attendance (AOR 0.5; 95 % CI 0.2, 0.9), being on antiretroviral therapy (AOR 0.01; 95 % CI 0.004, 0.04), CD4(+) T lymphocyte count 200-350 cells/mm(3) at care entry (AOR 0.3; 95 % 0.1, 0.9), and education (AOR 0.5; 95 % CI 0.2, 0.9). Variables predicting viremia included black race (AOR 3.2; 95 % CI 1.4, 7.4) and selective disclosure of HIV status (AOR 2.7; 95 % CI 1.2, 5.6). Church attendance may provide needed support for patients entering HIV care for the first time. El Sur Este de los Estados Unidos tiene tasas altas de visitas a iglesias y de infección por VIH. Evaluamos la relación entre visitas a iglesias y viremia por VIH en una cohorte de pacientes infectados con VIH en el Sur Este de los EEUU. La viremia (carga viral ≥ 200 copias/ml) fue analizada a los 12 meses de iniciar el cuidado médico. Los modelos de regresión logística univariado y multivariado fueron ajustados para variables potencialmente relacionadas a viremia. De 382 pacientes, 75 % tuvieron supresión virológica a los 12 meses. Variables que ofrecieron protección fueron visitas a iglesias (AOR 0.5; IC95 % 0.2-0.9), recibir terapia antiretroviral (AOR 0.01; IC95 % 0.004,0.04), recuento de linfocitos T CD4 + 200-350 al iniciar cuidado médico (AOR 0.3; IC95 % 0.1,09), y educación (AOR 0.5; IC95 % 0.2,0.9). Las variables que predijeron viremia incluyeron raza negra (AOR 3.2; IC95 % 1.4,7.4) y la comunicación selectiva del diagnóstico de VIH a otras personas (AOR 2.7; 95 % IC 1

  13. DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or 800/100mg once daily plus two NRTI.

    Science.gov (United States)

    Di Yacovo, Silvana; Molto, Jose; Ferrer, Elena; Curran, Adrian; Else, Laura Jayne; Clotet, Bonaventura; Tiraboschi, Juan; Niubo, Jordi; Vila, Antonia; Podzamczer, Daniel

    2014-01-01

    Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV-1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD. DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011-006272-39). Here we present the results of a CSF sub-study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20-28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high-performance liquid chromatography (HPLC). Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17-71) years, CD4 cell count 532 cells/mL (190-1,394). Median total time on DRV/r was 30 (11-57) months, and since the beginning of the study 8 (6-12) months in DRV800 and 10 (7-12) months in DRV600 patients. LP was performed a median of 26 (24-28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326-3,742) ng/mL, CSF levels 17.08 (5.79-30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028-0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958-3,910) ng/mL, CSF levels 13.23 (3.47-32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018-0.0262). All patients had VL100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in

  14. Crack initiation at high loading rates applying the four-point bending split Hopkinson pressure bar technique

    Science.gov (United States)

    Henschel, Sebastian; Krüger, Lutz

    2015-09-01

    Dynamic crack initiation with crack-tip loading rates of K˙ ≈ 2.106MPa√ms-1 in a high strength G42CrMoS4 steel was investigated. To this end, a previously developed split Hopkinson pressure bar with four-point bending was utilised. V-notched and pre-cracked Charpy specimens were tested. The detection of dynamic crack initiation was performed by analysing the dynamic force equilibrium between the incident and the transmission bar. Additionally, the signal of a near-field strain gauge and high-speed photography were used to determine the instant of crack initiation. To account for vibrations of the sample, a dynamic analysis of the stress intensity factor was performed. The dynamic and static analyses of the tests produced nearly the same results when a force equilibrium was achieved. Fracture-surface analysis revealed that elongated MnS inclusions strongly affected both the dynamic crack initiation and growth. Blunting of the precrack did not take place when a group of MnS inclusions was located directly at the precrack tip. Due to the direction of the elongated MnS inclusions perpendicular to the direction of crack growth, the crack could be deflected. The comparison with a 42CrMo4 steel without elongated MnS inclusions revealed the detrimental effect in terms of resistance to crack initiation. Taking the loading-rate dependency into consideration, it was shown that there was no pronounced embrittlement due to the high loading rates.

  15. Evaluating potential non-point source loading of PAHs from contaminated soils: a fugacity-based modeling approach.

    Science.gov (United States)

    Luo, Xiaolin; Zheng, Yi; Lin, Zhongrong; Wu, Bin; Han, Feng; Tian, Yong; Zhang, Wei; Wang, Xuejun

    2015-01-01

    Soils contaminated by Polycyclic Aromatic Hydrocarbons (PAHs) are subject to significant non-point source (NPS) pollution during rainfall events. Recent studies revealed that the classic enrichment ratio (ER) approach may not be applicable to PAHs. This study developed a model to estimate the ER of PAHs which innovatively applies the fugacity concept. The ER model has been validated with experimental data, which suggested that the transport of PAHs not only depends on their physicochemical properties, but on the sediment composition and how the composition evolves during the event. The modeling uncertainty was systematically examined, and found to be highly compound-dependent. Based on the ER model, a strategy was proposed to practically evaluate the potential NPS loading of PAHs in watersheds with heterogeneous soils. The study results have important implications to modeling and managing the NPS pollution of PAHs (or other chemicals alike) at a watershed scale. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. STRUTEX: A prototype knowledge-based system for initially configuring a structure to support point loads in two dimensions

    Science.gov (United States)

    Rogers, James L.; Feyock, Stefan; Sobieszczanski-Sobieski, Jaroslaw

    1988-01-01

    The purpose of this research effort is to investigate the benefits that might be derived from applying artificial intelligence tools in the area of conceptual design. Therefore, the emphasis is on the artificial intelligence aspects of conceptual design rather than structural and optimization aspects. A prototype knowledge-based system, called STRUTEX, was developed to initially configure a structure to support point loads in two dimensions. This system combines numerical and symbolic processing by the computer with interactive problem solving aided by the vision of the user by integrating a knowledge base interface and inference engine, a data base interface, and graphics while keeping the knowledge base and data base files separate. The system writes a file which can be input into a structural synthesis system, which combines structural analysis and optimization.

  17. Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study.

    Science.gov (United States)

    Assoumou, L; Charpentier, C; Recordon-Pinson, P; Grudé, M; Pallier, C; Morand-Joubert, L; Fafi-Kremer, S; Krivine, A; Montes, B; Ferré, V; Bouvier-Alias, M; Plantier, J-C; Izopet, J; Trabaud, M-A; Yerly, S; Dufayard, J; Alloui, C; Courdavault, L; Le Guillou-Guillemette, H; Maillard, A; Amiel, C; Vabret, A; Roussel, C; Vallet, S; Guinard, J; Mirand, A; Beby-Defaux, A; Barin, F; Allardet-Servent, A; Ait-Namane, R; Wirden, M; Delaugerre, C; Calvez, V; Chaix, M-L; Descamps, D; Reigadas, S

    2017-06-01

    Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.

    Science.gov (United States)

    Towner, Jonathan S; Rollin, Pierre E; Bausch, Daniel G; Sanchez, Anthony; Crary, Sharon M; Vincent, Martin; Lee, William F; Spiropoulou, Christina F; Ksiazek, Thomas G; Lukwiya, Mathew; Kaducu, Felix; Downing, Robert; Nichol, Stuart T

    2004-04-01

    The largest outbreak on record of Ebola hemorrhagic fever (EHF) occurred in Uganda from August 2000 to January 2001. The outbreak was centered in the Gulu district of northern Uganda, with secondary transmission to other districts. After the initial diagnosis of Sudan ebolavirus by the National Institute for Virology in Johannesburg, South Africa, a temporary diagnostic laboratory was established within the Gulu district at St. Mary's Lacor Hospital. The laboratory used antigen capture and reverse transcription-PCR (RT-PCR) to diagnose Sudan ebolavirus infection in suspect patients. The RT-PCR and antigen-capture diagnostic assays proved very effective for detecting ebolavirus in patient serum, plasma, and whole blood. In samples collected very early in the course of infection, the RT-PCR assay could detect ebolavirus 24 to 48 h prior to detection by antigen capture. More than 1,000 blood samples were collected, with multiple samples obtained from many patients throughout the course of infection. Real-time quantitative RT-PCR was used to determine the viral load in multiple samples from patients with fatal and nonfatal cases, and these data were correlated with the disease outcome. RNA copy levels in patients who died averaged 2 log(10) higher than those in patients who survived. Using clinical material from multiple EHF patients, we sequenced the variable region of the glycoprotein. This Sudan ebolavirus strain was not derived from either the earlier Boniface (1976) or Maleo (1979) strain, but it shares a common ancestor with both. Furthermore, both sequence and epidemiologic data are consistent with the outbreak having originated from a single introduction into the human population.

  19. Self-reported adherence and pharmacy refill adherence are both predictive for an undetectable viral load among HIV-infected migrants receiving cART.

    Directory of Open Access Journals (Sweden)

    Sabrina K Been

    Full Text Available HIV-infected migrants were shown to have poorer treatment outcomes than Dutch HIV-infected patients, often due to worse treatment adherence. Self-reported adherence would be an easy way to monitor adherence, but its validity relative to pharmacy refill adherence has not been extensively evaluated in migrants. All HIV-infected migrants older than 18 years and in care at the two Rotterdam HIV-treatment centers were eligible. Refill data with leftover medication (PRL (residual pill count were obtained from their pharmacies up to 15 months prior to inclusion. Self-reported adherence to combination Antiretroviral Therapy was assessed by four questions about adherence at inclusion. Additionally, risk factors for pharmacy refill non-adherence were examined. In total, 299 HIV-infected migrants were included. Viral load (VL was detectable in 11% of the patients. Specificity of PRL was 53% for patients with an adherence of 100% and decreased with lower cut-off values. Sensitivity and negative predictive value (NPV were 68% and 15% and increased with lower cut-off values. Positive predictive value (PPV was around 93% for all cut-off values. Using the self-reported questions, 139 patients (47% reported to be adherent. Sensitivity was 49% and specificity was 72%. PPV and NPV were 95% and 13%. No risk factors for pharmacy refill non-adherence were found in multivariable analyses. Both PRL and self-reported adherence, can predict undetectable VL in HIV-infected migrants. PPV and NPV are similar for both methods. This study shows that using four self-reported items is sufficient to predict adherence which is crucial for optimal clinical outcome in HIV-infected migrants.

  20. Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

    Science.gov (United States)

    Koller, Manuel; Fatti, Geoffrey; Chi, Benjamin H; Keiser, Olivia; Hoffmann, Christopher J; Wood, Robin; Prozesky, Hans; Stinson, Kathryn; Giddy, Janet; Mutevedzi, Portia; Fox, Matthew P; Law, Matthew; Boulle, Andrew; Egger, Matthias

    2015-11-01

    HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.

  1. New design, development, and optimization of an in-house quantitative TaqMan Real-time PCR assay for HIV-1 viral load measurement.

    Science.gov (United States)

    Noorbazargan, Hassan; Nadji, Seyed Alireza; Samiee, Siamak Mirab; Paryan, Mahdi; Mohammadi-Yeganeh, Samira

    2018-02-23

    Background Viral load measurement is commonly applicable to monitor HIV infection in patients to determine the number of HIV-RNA in serum samples of individuals. The aim of the present study was to set up a highly specific, sensitive, and reproducible home-brewed Real-time PCR assay based on TaqMan chemistry to quantify HIV-1 RNA genome. Methods In this study, three sets of primer pairs and a TaqMan probe were designed for HIV subtypes conserved sequences. An internal control was included in this assay to evaluate the presence of inhibition. Standard curve and threshold cycle values were determined using in vitro transcribed RNA from int region of HIV-1. A serial dilution of RNA standards was generated by in vitro transcription, from 10 to 10 9 copies/ml to find the sensitivity and the limit of detection (LOD) of the assay and to evaluate its performance in a quantitative RT-PCR assay. Results The assay has a low LOD equivalent to 33.13 copies/ml of HIV-1 RNA and a linear range of detection from 10 to 10 9 copies/ml. The coefficient of variation (CV) for Inter and Intra-assay precision of this in-house HIV Real-time RT-PCR ranged from 0.28 to 2.49% and 0.72 to 4.47%, respectively. The analytical and clinical specificity was 100%. Conclusions The results indicate that the developed method has a suitable specificity and sensitivity and is highly reproducible and cost-benefit. Therefore, it will be useful to monitor HIV infection in plasma samples of individuals.

  2. Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings

    Science.gov (United States)

    Koller, Manuel; Fatti, Geoffrey; Chi, Benjamin H; Keiser, Olivia; Hoffmann, Christopher J; Wood, Robin; Prozesky, Hans; Stinson, Kathryn; Giddy, Janet; Mutevedzi, Portia; Fox, Matthew; Law, Matthew; Boulle, Andrew; Egger, Matthias

    2017-01-01

    Background HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. Methods We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. Findings 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. Interpretation CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited. PMID:26470034

  3. CD4 and viral load dynamics in antiretroviral-naïve HIV-infected adults from Soweto, South Africa: a prospective cohort.

    Science.gov (United States)

    Martinson, Neil A; Gupte, Nikhil; Msandiwa, Reginah; Moulton, Lawrence H; Barnes, Grace L; Ram, Malathi; Gray, Glenda; Hoffmann, Chris; Chaisson, Richard E

    2014-01-01

    CD4 count is a proxy for the extent of immune deficiency and declines in CD4 count are a measure of disease progression. Decline in CD4 count is an important component: for estimating benefits of ARV treatment; for individual level counselling on the rapidity of untreated disease progression and prognosis; and can be used in planning demand for health services. Our objective is to report CD4 decline and changes in viral load (VL) in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates. HIV-infected, tuberculin skin test positive adults who were not eligible for antiretroviral (ARV) treatment were randomized to a trial of preventive treatment from 2003-2005. VL and CD4 count were assessed at enrollment and CD4 counts repeated at least annually. During follow-up, individuals whose CD4 counts decreased to alcohol use had little impact on the estimate of CD4 decline. However, VL at baseline had a major impact on CD4 decline. The percent decline in CD4 count was 13.3% (95% CI 12.0%, 14.7%), 10.6% (95% CI 8.8%, 12.4%), and 13.8% (95% CI 12.1%, 15.5%) per annum for baseline VLs of 100,000 (N = 122) copies/ml. Our data suggests that six and a half years will elapse for an individual's CD4 count to decline from 750 to 350 cells/mm3 in the absence of ART.

  4. Associations Between Medicare Part D and Out-of-Pocket Spending, HIV Viral Load, Adherence, and ADAP Use in Dual Eligibles With HIV.

    Science.gov (United States)

    Belenky, Nadya; Pence, Brian W; Cole, Stephen R; Dusetzina, Stacie B; Edmonds, Andrew; Oberlander, Jonathan; Plankey, Michael W; Adedimeji, Adebola; Wilson, Tracey E; Cohen, Jennifer; Cohen, Mardge H; Milam, Joel E; Golub, Elizabeth T; Adimora, Adaora A

    2018-01-01

    The implementation of Medicare part D on January 1, 2006 required all adults who were dually enrolled in Medicaid and Medicare (dual eligibles) to transition prescription drug coverage from Medicaid to Medicare part D. Changes in payment systems and utilization management along with the loss of Medicaid protections had the potential to disrupt medication access, with uncertain consequences for dual eligibles with human immunodeficiency virus (HIV) who rely on consistent prescription coverage to suppress their HIV viral load (VL). To estimate the effect of Medicare part D on self-reported out-of-pocket prescription drug spending, AIDS Drug Assistance Program (ADAP) use, antiretroviral adherence, and HIV VL suppression among dual eligibles with HIV. Using 2003-2008 data from the Women's Interagency HIV Study, we created a propensity score-matched cohort and used a difference-in-differences approach to compare dual eligibles' outcomes pre-Medicare and post-Medicare part D to those enrolled in Medicaid alone. Transition to Medicare part D was associated with a sharp increase in the proportion of dual eligibles with self-reported out-of-pocket prescription drug costs, followed by an increase in ADAP use. Despite the increase in out-of-pocket costs, both adherence and HIV VL suppression remained stable. Medicare part D was associated with increased out-of-pocket spending, although the increased spending did not seem to compromise antiretroviral therapy adherence or HIV VL suppression. It is possible that increased ADAP use mitigated the increase in out-of-pocket spending, suggesting successful coordination between Medicare part D and ADAP as well as the vital role of ADAP during insurance transitions.

  5. DIGESTIÓN ANAEROBIA DE LACTOSUERO: EFECTO DE ALTAS CARGAS PUNTUALES ANAEROBIC DIGESTION OF WHEY: EFFECT OF HIGH POINT LOADS

    Directory of Open Access Journals (Sweden)

    Ricardo Adolfo Parra Huertas

    2010-06-01

    for wastewater treatment mainly of dietary origin. The work was aimed at determining the behavior of the anaerobic treatment system when incorporating whey high point loads. Acid whey was used, which fed the two-stage system, and anaerobic biofilter reactor UASB. 3 charges were handled constant of 5,200 mg COD / L.day, 7,800 mg COD / L.day and 10.500 mg COD / L.day; on each charge is applied 3 point charges whey acid: 5,700 mg COD / L.day, 26,300 mg COD / L.day and 34,200 mg COD / L.day, each with a duration of 24 hours. The hydraulic retention time of the system was 2.9 days, the pH value for the influent of constant point charges was 7.0 and adding sodium bicarbonate prior to the effluent, the pH at constant loads was 7.6 and 7.7 for loads point. The operating temperature was in the range of 15-20 °C. In the constant loads (CC elimination of COD was 57% and point charges (PC 82%. Sugar efficiency was 99% in CA and PC. Protein removal was 64% for CC and CP 89%. Volatile fatty acids in the CC had a concentration of 403 mg/L in the influent and effluent concentration of 3,156 mg/L in the influent introduced the CP concentration of 572 mg/L and the effluent 4,492 mg/L. The two-stage system endured until the point charges 6.5 times the constant load without reducing their efficiency; however, the efficiencies in the response variable were above the constant organic loads, noting that the proposed scheme is a good option for treatment with whey wastewater discharges could bear pure whey, so it can be recommended for cheese producers.

  6. Adaptation to Elastic Loads and BMI Robot Controls During Rat Locomotion examined with Point-Process GLMs.

    Directory of Open Access Journals (Sweden)

    Weiguo eSong

    2015-04-01

    Full Text Available Currently little is known about how a mechanically coupled BMI system’s actions are integrated into ongoing body dynamics. We tested a locomotor task augmented with a BMI system driving a robot mechanically interacting with a rat under three conditions: control locomotion (BL, ‘simple elastic load’ (E and ‘BMI with elastic load’ (BMI/E. The effect of the BMI was to allow compensation of the elastic load as a function of the neural drive. Neurons recorded here were close to one another in cortex, all within a 200 micron diameter horizontal distance of one another. The interactions of these close assemblies of neurons may differ from those among neurons at longer distances in BMI tasks and thus are important to explore. A point process generalized linear model (GLM, was used to examine connectivity at two different binning timescales (1ms vs. 10ms. We used GLM models to fit non-Poisson neural dynamics solely using other neurons’ prior neural activity as covariates. Models at different timescales were compared based on Kolmogorov-Smirnov (KS goodness-of-fit and parsimony. About 15% of cells with non-Poisson firing were well fitted with the neuron-to-neuron models alone. More such cells were fitted at the 1ms binning than 10ms. Positive connection parameters (‘excitation’ ~70% exceeded negative parameters (‘inhibition’ ~30%. Significant connectivity changes in the GLM determined networks of well-fitted neurons occurred between the conditions. However, a common core of connections comprising at least ~15% of connections persisted between any two of the three conditions. Significantly almost twice as many connections were in common between the two load conditions (~27%, compared to between either load condition and the baseline. This local point process GLM identified neural correlation structure and the changes seen across task conditions in the rats in this neural subset may be intrinsic to cortex or due to feedback and input

  7. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

    Directory of Open Access Journals (Sweden)

    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  8. Viral Polymerases

    Science.gov (United States)

    Choi, Kyung H.

    2016-01-01

    Viral polymerases play a central role in viral genome replication and transcription. Based on the genome type and the specific needs of particular virus, RNA-dependent RNA polymerase, RNA-dependent DNA polymerase, DNA-dependent RNA polymerase, and DNA-dependent RNA polymerases are found in various viruses. Viral polymerases are generally active as a single protein capable of carrying out multiple functions related to viral genome synthesis. Specifically, viral polymerases use variety of mechanisms to recognize initial binding sites, ensure processive elongation, terminate replication at the end of the genome, and also coordinate the chemical steps of nucleic acid synthesis with other enzymatic activities. This review focuses on different viral genome replication and transcription strategies, and the polymerase interactions with various viral proteins that are necessary to complete genome synthesis. PMID:22297518

  9. Hepatitis C viral load does not predict disease outcome: going beyond numbers A carga viral do vírus da hepatite C não prediz a evolução: indo além dos números

    Directory of Open Access Journals (Sweden)

    Evaldo Stanislau Affonso de ARAÚJO

    2002-04-01

    Full Text Available The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index. Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins, host (sex, age, weight, etc and treatment variables (dosage, time of treatment, type of interferon within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.Através da análise de 58 pacientes tratados com Interferon Alfa em função de hepatite C crônica e sem cirrose, demonstramos que a carga viral do Vírus da Hepatite C (VHC não se correlacionou com a evolução histológica da doença (p = 0,6559 para alterações arquiteturais e p = 0,6271 para o Índice de Atividade Histológica-IAH. Assim a utilização da quantificação do RNA viral como preditor evolutivo ou determinante da gravidade da hepatite C é incorreto e de valor relativo. Revisando o tema encontramos variáveis do VHC (genótipo, heterogeneidade e mutantes, proteínas específicas, do hospedeiro (sexo, idade, peso, etc e dos medicamentos (posologia, tempo de tratamento, tipo de Interferon fundamentais e interdependentes, inseridas no contexto mais amplo da cinética viral, da resposta imunológica mediada pelo Interferon (al

  10. Self-entanglement of long linear DNA vectors using transient non-B-DNA attachment points: a new concept for improvement of non-viral therapeutic gene delivery.

    Science.gov (United States)

    Tolmachov, Oleg E

    2012-05-01

    The cell-specific and long-term expression of therapeutic transgenes often requires a full array of native gene control elements including distal enhancers, regulatory introns and chromatin organisation sequences. The delivery of such extended gene expression modules to human cells can be accomplished with non-viral high-molecular-weight DNA vectors, in particular with several classes of linear DNA vectors. All high-molecular-weight DNA vectors are susceptible to damage by shear stress, and while for some of the vectors the harmful impact of shear stress can be minimised through the transformation of the vectors to compact topological configurations by supercoiling and/or knotting, linear DNA vectors with terminal loops or covalently attached terminal proteins cannot be self-compacted in this way. In this case, the only available self-compacting option is self-entangling, which can be defined as the folding of single DNA molecules into a configuration with mutual restriction of molecular motion by the individual segments of bent DNA. A negatively charged phosphate backbone makes DNA self-repulsive, so it is reasonable to assume that a certain number of 'sticky points' dispersed within DNA could facilitate the entangling by bringing DNA segments into proximity and by interfering with the DNA slipping away from the entanglement. I propose that the spontaneous entanglement of vector DNA can be enhanced by the interlacing of the DNA with sites capable of mutual transient attachment through the formation of non-B-DNA forms, such as interacting cruciform structures, inter-segment triplexes, slipped-strand DNA, left-handed duplexes (Z-forms) or G-quadruplexes. It is expected that the non-B-DNA based entanglement of the linear DNA vectors would consist of the initial transient and co-operative non-B-DNA mediated binding events followed by tight self-ensnarement of the vector DNA. Once in the nucleoplasm of the target human cells, the DNA can be disentangled by type II

  11. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  12. Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

    Science.gov (United States)

    Poon, Art F Y; Aldous, Jeannette L; Mathews, W Christopher; Kitahata, Mari; Kahn, James S; Saag, Michael S; Rodríguez, Benigno; Boswell, Stephen L; Frost, Simon D W; Haubrich, Richard H

    2011-01-01

    Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log₁₀pVL) and D67N/G (-2.1[³√CD4] and 0.4 log₁₀pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and

  13. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  14. Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

    Directory of Open Access Journals (Sweden)

    Art F Y Poon

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL and CD4+ cell count (CD4 at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184 were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log₁₀pVL and D67N/G (-2.1[³√CD4] and 0.4 log₁₀pVL were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1

  15. The JCPYV DNA load inversely correlates with the viral microrna expression in blood and cerebrospinal fluid of patients at risk of PML.

    Science.gov (United States)

    Rocca, Arianna; Martelli, Francesco; Delbue, Serena; Ferrante, Pasquale; Bartolozzi, Dario; Azzi, Alberta; Giannecchini, Simone

    2015-09-01

    In light of their regulatory role, changes in the expression of Polyomavirus JC (JCPyV) microRNAs may be relevant for virus reactivation and the development of progressive multifocal leukoencephalopathy (PML). To investigate the presence of JCPyV-DNA and JCPyV microRNA expression in clinical specimens of patients at risk for PML. The JCPyV-DNA and microRNA status was assessed in peripheral blood mononuclear cells (PBMCs) and plasma from 100 HIV patients, in serum and cerebrospinal fluid (CSF) from 14 HIV PML patients and in PBMCs and plasma from 50 healthy controls using Multiplex real-time PCR and JCPyV miRNA-J1-3p and -5p stem-loop RT-PCR. The JCPyV-DNA microRNA-expressing region was also sequenced. A positive JCPyV-DNA status was more prevalent in HIV patients (67%, 67/100) compared to healthy controls (18%, 9/50). Among these, 46% and 42% of the HIV patients and 18% and 0% of the healthy controls were positive based on PBMC and plasma determinations, respectively. PBMC JCPyV microRNA positivity was observed in 22 out of 46 (48%) JCPyV+ HIV patients and in 3 out of 9 (33%) JCPyV+ healthy controls. Moreover, JCPyV microRNAs in exosomes were found in 6 out of 100 (6%) HIV plasma samples, in 12 out of 50 (24%) healthy samples, in 6 out of 14 (43%) serum samples, and in 3 out of 5 (60%) HIV PML CSF samples. Of note, the JCPyV-DNA load was inversely correlated with expression of the viral microRNA. The JCPyV microRNA genomic expression region showed a different combination of three mutations. The low levels of JCPyV microRNA expression in HIV patients with high JCPyV-DNA prevalence observed in this study highlight the potential clinical relevance of JCPyV microRNAs in PML risk assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Mitochondrial DNA mutation load in a family with the m.8344A>G point mutation and lipomas

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Al-Hashimi, Noor; Duno, Morten

    2017-01-01

    Studies have shown that difference in mtDNA mutation load among tissues is a result of postnatal modification. We present five family members with the m.8344A>G with variable phenotypes but uniform intrapersonal distribution of mutation load, indicating that there is no postnatal modification of mt......DNA mutation load in this genotype....

  17. Synoptic monitoring as an approach to discriminating between point and diffuse source contributions to zinc loads in mining impacted catchments.

    Science.gov (United States)

    Banks, V J; Palumbo-Roe, B

    2010-09-01

    One of the global legacies of industrialisation is the environmental impacts of historic mineral exploitation. Recent national initiatives to manage the impacts on ground and surface waters have driven the need to develop better techniques for assessing understanding of the catchment-scale distribution and characterisation of the relative contribution of point and diffuse contaminant sources. The benefits of a detailed, multidisciplinary investigation are highlighted through a case study focused on the Rookhope Burn, a tributary of the River Wear, which falls within a significantly mine impacted area of the North Pennines Orefield, UK. Zinc (Zn) has been identified as the contaminant of concern within this catchment, which is judged by the Environment Agency to be at risk of failing to achieve good water quality status in the context of the Water Framework Directive. The results of synoptic flow monitoring and sampling for chemical determinations of major and trace elements have been used to calculate mass balances of instream and inflow chemical loads in the Rookhope Burn. Despite a dominant impact on the water quality from a mine outburst (especially Zn [1.45 to 2.42 mg/l], Fe [2.18 to 3.97 mg/l], Mn [3.69 to 6.77 mg/l], F [3.99 to 4.80 mg/l] and SO(4) [178 to 299 mg/l]), mass balance calculations combined with geological mapping have facilitated the identification of significant, previously unknown, subsurface contributions of Zn contaminated groundwater (with Zn concentrations in excess of 0.4 to 0.9 mg/l and 0.18 to 0.36 mg/l) to the Burn. The subsurface contributions exhibit spatial correspondence to mine workings with associated mineral veins and adits, or to points of suspected karst groundwater resurgence. These findings reiterate the challenges posed in decision making with respect to remediation, in this case in the context of the management of significant subsurface contributions.

  18. Estimation of the strength of Nubian sandstone formation from point load test index and other simple parameters

    Directory of Open Access Journals (Sweden)

    Zein Abdul Karim M.

    2018-01-01

    Full Text Available This study investigates the correlation of the uniaxial compressive strength (UCS and the point load test (PLT index Is(50, bulk density, water absorption and the RQD properties of the Sudanese Nubian sandstone formation. The UCS being is the rock property needed in engineering practice but its determination is tedious, time consuming and expensive. Alternatively, the UCS may be indirectly evaluated through establishing relationships with rock parameters which are easier, cheaper and more convenient to determine in the laboratory or in the field. An extensive laboratory testing was executed to determine the above rock properties for many NSF samples taken from Khartoum State and other areas. Statistical analysis was performed on the test data and a reliable linear regression equation has been developed with a UCS to PLT Is(50 conversion factor of 10.18 and may be applied to estimate the strength of the Sudanese sandstone formation. The developed correlation is in good agreement with few of the many methods published for similar rock types which indicates that large errors may result in from applying an inappropriate UCS prediction method. Thus, it is important to establish separate correlations or validate published correlations to check their suitability for a specific rock types and local geologies. Useful correlation relationships of reasonable accuracy were also established for rough estimation of the UCS from the bulk density, water absorption and the RQD properties of the Nubian sandstone formation.

  19. Optimal Load Shedding in Deregulated System and Consideration of Effective Factors by Using a Predictor-Corrector Interior-Point Method (IPM

    Directory of Open Access Journals (Sweden)

    Mojtaba Afshari

    2010-07-01

    Full Text Available In this paper, intifially an introduction is presented about Electric Power market in deregulated system and load shedding by interior-point method in these systems. Then, predictor-corrector of IPM is considered and by consideration of the IEEE 6 busbar network, distribution of load by using software (PSAT will be considered. Then, with introduction of bilateral contracts in organized renewal system, the proposed method is applied to make optimal load shedding in the IEEE 30 busbar network. In this direction, the effective factors on changes of load- shedding model are analyzed completely. Some of factors are price changes, congestion lines (result from emitting of one or more lines and maximum load-shedding limit in each bus bar.

  20. Investigation into dynamic response of a three-point bend specimen in a Hopkinson bar loaded fracture test using numerical methods

    Directory of Open Access Journals (Sweden)

    Raja Ahsan Javed

    2015-07-01

    Full Text Available Dynamic fracture toughness of engineering materials at loading rates greater than 10 6 MPa m / s is widely investigated using the modified Hopkinson pressure bar apparatus. For accurate measurement of dynamic fracture toughness, it is essential to thoroughly understand the dynamic effects excited by the stress wave, such as stress wave propagation characteristics in bars/cracked specimen, the contact situation between the specimen and loading point or supports, and the dynamic response of the fracture specimen. In this work, full transient dynamic analysis techniques are used to comprehend “loss of contact” situation of cracked fracture specimen with an incident bar (impactor and a transmission bar (supports in a Hopkinson bar loaded two-bar/three-point bend test. A modified Hopkinson bar loaded experimental setup, including striker, incident, and transmission bars and three-point bend fracture specimen, is modeled using the commercial software ANSYS. The dynamic responses of the specimens made of titanium alloy, high-strength steel, and aluminum alloy are analyzed, and the specimen contact states with the incident and transmission bars are investigated using stress state contours of the specimen along with nodal displacement of the specimen and the bars. The dynamic fracture toughness values for the three specimens are also calculated and compared with the experimental results. The simulation results from the current two-bar/three-point bend test indicated that no “loss of contact” occurs during the first load duration as is previously proved experimentally.

  1. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  2. Pemasaran ViralViral Marketing

    OpenAIRE

    Situmorang, James Rianto

    2010-01-01

    Viral marketing is an extremely powerful and effective form of internet marketing. Itis a new form of word-of-mouth through internet. In viral marketing, someone passeson a marketing message to someone else and so on. Viral marketing proposes thatmessages can be rapidly disseminated from consumer to consumer leading to largescale market acceptance. The analogy of a virus is used to described the exponentialdiffusion of information in an electronic environment and should not be confusedwith th...

  3. Enhancing patient navigation to improve intervention session attendance and viral load suppression of persons with HIV and substance use: a secondary post hoc analysis of the Project HOPE study.

    Science.gov (United States)

    Stitzer, Maxine; Matheson, Tim; Cunningham, Colin; Sorensen, James L; Feaster, Daniel J; Gooden, Lauren; Hammond, Alexis S; Fitzsimons, Heather; Metsch, Lisa R

    2017-06-27

    Interventions are needed to improve viral suppression rates among persons with HIV and substance use. A 3-arm randomized multi-site study (Metsch et al. in JAMA 316:156-70, 2016) was conducted to evaluate the effect on HIV outcomes of usual care referral to HIV and substance use services (N = 253) versus patient navigation delivered alone (PN: N = 266) or together with contingency management (PN + CM; N = 271) that provided financial incentives targeting potential behavioral mediators of viral load suppression. This secondary analysis evaluates the effects of financial incentives on attendance at PN sessions and the relationship between session attendance and viral load suppression at end of the intervention. Frequency of sessions attended was analyzed over time and by distribution of individual session attendance frequency (PN vs PN + CM). Percent virally suppressed (≤200 copies/mL) at 6 months was compared for low, medium and high rate attenders. In PN + CM a total of $220 could be earned for attendance at 11 PN sessions over the 6-month intervention with payments ranging from $10 to $30 under an escalating schedule. The majority (74%) of PN-only participants attended 6 or more sessions but only 28% attended 10 or more and 16% attended all eleven sessions. In contrast, 90% of PN + CM attended 6 or more visits, 69% attended 10 or more and 57% attended all eleven sessions (attendance distribution χ 2 [11] = 105.81; p Study results support use of attendance incentives to improve rates of contact between service providers and patients, particularly patients who are difficult to engage in care. Trial Registration clinicaltrials.govIdentifier: NCT01612169.

  4. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  5. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  6. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naïve HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Science.gov (United States)

    He, Lai; Zhao, Jin; Wang, Maggie Haitian; Siu, Kenny K Y; Gan, Yong-Xia; Chen, Lin; Zee, Benny C Y; Yang, Li; Kung, Hsiang-Fu; Yang, Zheng-Rong; He, Ming-Liang

    2014-01-01

    Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  7. LONGER DURATION OF HOMELESSNESS IS ASSOCIATED WITH A LOWER LIKELIHOOD OF NON-DETECTABLE PLASMA HIV-1 RNA VIRAL LOAD AMONG PEOPLE WHO USE ILLICIT DRUGS IN A CANADIAN SETTING

    OpenAIRE

    Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M.-J.

    2016-01-01

    Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records in...

  8. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens

    Science.gov (United States)

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens by activating natural killer cells (NK), cytotoxic T lymphocytes, and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such i...

  9. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    NARCIS (Netherlands)

    Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen; Libin, Pieter; van de Vijver, David A. M. C.; Albert, Jan; Asjö, Birgitta; Balotta, Claudia; Bruckova, Marie; Camacho, Ricardo J.; Clotet, Bonaventura; Coughlan, Suzie; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzei; Korn, Klaus; Kostrikis, Leondios G.; Kücherer, Claudia; Nielsen, Claus; Paraskevis, Dimitrios; Poljak, Mario; Puchhammer-Stockl, Elisabeth; Riva, Chiara; Ruiz, Lidia; Liitsola, Kirsi; Schmit, Jean-Claude; Schuurman, Rob; Sönnerborg, Anders; Stanekova, Danica; Stanojevic, Maja; Struck, Daniel; van Laethem, Kristel; Wensing, Annemarie M. J.; Boucher, Charles A. B.; Vandamme, Anne-Mieke; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. -M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; de Roo, A.; de Wit, S.; Deforche, K.; Echahidi, F.; Fransen, K.; Goffard, J. -C.; Goubau, P.; Goudeseune, E.; Yombi, J. -C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; van den Heuvel, A.; van der Gucht, B.; van Ranst, M.; van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; van Laethem, K.; Kostrikis, L.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, Marek; Bruckova, M.; Machala, L.; Nielsen, C.; Jrgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Daümer, M.; Eberle, J.; Hamouda, O.; Heiken, H.; Kaiser, R.; Knechten, H.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Hatzakis, A.; Paraskevis, D.; Magiorkinis, E.; Hatzitheodorou, E.; Issaris, C.; Haida, C.; Zavitsanou, A.; Magiorkinis, G.; Lazanas, M.; Chini, M.; Magafas, N.; Tsogas, N.; Paparizos, V.; Kourkounti, S.; Antoniadou, A.; Papadopoulos, A.; Panagopoulos, P.; Poulakou, G.; Sakka, V.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Lelekis, M.; Xilomenos, G.; Psichogiou, M.; Daikos, G. L.; Panos, G.; Haratsis, G.; Kordossis, T.; Kontos, A.; Koratzanis, G.; Theodoridou, M.; Mostrou, G.; Spoulou, V.; de Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; Coughlan, S.; Grossman, Z.; Levi, I.; Chemtob, D.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Schmit, J. C.; Struck, D.; Hemmer, R.; Arendt, V.; Staub, T.; Schneider, F.; Roman, F.; Wensing, A. M. J.; Boucher, C. A. B.; van de Vijver, D. A. M. C.; van Bentum, P. H. M.; Brinkman, K.; Op de Coul, E. L.; van der Ende, M. E.; Hoepelman, I. M.; van Kasteren, M.; Juttmann, J.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M. W. J.; Schrijnders-Gudde, L.; Schuurman, R.; van de Ven, B. J. M.; Åsjö, B.; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Malolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Stanojevic, M.; Jevtovic, D. J.; Salemovic, D.; Stanekova, D.; Habekova, M.; Mokras, M.; Truska, P.; Poljak, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Karner, P.; Clotet, B.; Gutiérrez, C.; de Mendoza, C.; Erkicia, I.; Domingo, P.; Camino, X.; Galindo, M. J.; Blanco, J. L.; Leal, M.; Masabeu, A.; Guelar, A.; Llibre, J. M.; Margall, N.; Iribarren, J. A.; Gutierrez, S.; Baldoví, J. F.; Pedreira, J. D.; Gatell, J. M.; Moreno, S.; Soriano, V.; Ruiz, L.; Albert, J.; Blaxhult, A.; Heidarian, A.; Karlsson, A.; Aperia-Peipke, K.; Bergbrant, I. -M.; Gisslén, M.; Svennerholm, B.; Björkman, P.; Bratt, G.; Carlsson, M.; Ekvall, H.; Ericsson, M.; Höfer, M.; Johansson, B.; Sonnerbörg, A.; Kuylenstierna, N.; Ljungberg, B.; Mäkitalo, S.; Strand, A.; Öberg, S.

    2012-01-01

    The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already

  10. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    NARCIS (Netherlands)

    K. Theys (Kristof); K. Deforche; J. Vercauteren (Jurgen); P. Libin (Pieter); D.A.M.C. van de Vijver (David); J. Albert (Jan); B. Åsjö (Birgitta); M. Bruckova (Marie); R.J. Camacho (Ricardo Jorge); B. Clotet (Bonaventura); Z. Grossman (Zehava); A. Horban (Andrzej); C. Kücherer (Claudia); D. Paraskevis (Dimitrios); E. Puchhammer-Stöckl (Elisabeth); C. Riva (Chiara); L. Ruiz (Lidia); J.-C. Schmit (Jean-Claude); R. Schuurman (Rob); A. Sonnerborg (Anders); D. Stanekova (Danica); D. Struck (Daniel); K. van Laethem (Kristel); A.M.J. Wensing (Annemarie); E. Puchhammer-Stockl E. (Elisabeth); M. Sarcletti (M.); B. Schmied (B.); M. Geit (M.); G. Balluch (G.); A.M. Vandamme (Anne Mieke); I. Derdelinck (Inge); A. Sasse (A.); M. Bogaert (M.); H. Ceunen (H.); A. de Roo (Annie); M. De Wit (Meike); F. Echahidi (F.); K. Fransen (K.); J.-C. Goffard (J.); P. Goubau (Patrick); E. Goudeseune (E.); J.-C. Yombi (J.); P. Lacor (Patrick); C. Liesnard (C.); M. Moutschen (M.); L.A. Pierard; R. Rens (R.); J. Schrooten; D. Vaira (D.); A. van den Heuvel (A.); B. van der Gucht (B.); M. van Ranst (Marc); E. van Wijngaerden (Eric); T. Vandercam; M. Vekemans (M.); C. Verhofstede; N. Clumeck (N.); K. van Laethem (K.); L.G. Kostrikis (Leondios); I. Demetriades (I.); I. Kousiappa (Ioanna); V.L. Demetriou (Victoria); J. Hezka (Johana); M. Linka (Marek); L. Machala (L.); L.B. Jrgensen (L.); J. Gerstoft (J.); L. Mathiesen (L.); C. Pedersen (Court); C. Nielsen (Claus); A. Laursen (A.); B. Kvinesdal (B.); K. Liitsola (Kirsi); M. Ristola (M.); J. Suni (J.); J. Sutinen (J.); K. Korn (Klaus); C. K̈ucherer (C.); P. Braun (P.); G. Poggensee (G.); M. Däumer (M.); D. Eberle (David); O. Hamouda (Osamah); H. Heiken (H.); R. Kaiser (Rolf); H. Knechten (H.); H. M̈uller (H.); S. Neifer (S.); H. Walter (Hauke); B. Gunsenheimer-Bartmeyer (B.); T. Harrer (T.); A. Hatzakis (Angelos); E. Hatzitheodorou (E.); C. Issaris (C.); C. Haida (C.); A. Zavitsanou (A.); G. Magiorkinis (Gkikas); M. Lazanas (M.); L. Chini; N. Magafas (N.); N. Tsogas (N.); V. Paparizos (V.); S. Kourkounti (S.); A. Antoniadou (A.); A. Papadopoulos (A.); P. Panagopoulos (P.); G. Poulakou (G.); V. Sakka (V.); G. Chryssos (G.); S. Drimis (S.); P. Gargalianos (P.); M. Lelekis (M.); G. Xilomenos (G.); M. Psichogiou (M.); G.L. Daikos (G.); G. Panos (G.); G. Haratsis (G.); T. Kordossis (T.); A. Kontos (Angelos); G. Koratzanis (G.); M. Theodoridou (M.); G. Mostrou (G.); V. Spoulou (V.); W. Hall (W.); C. de Gascun (Cillian); C. Byrne (C.); M. Duffy (M.); P. Bergin; D. Reidy (D.); G. Farrell; J. Lambert (Julien); E. O'Connor (E.); A. Rochford (A.); J. Low (J.); P. Coakely (P.); S. Coughlan (Suzie); I. Levi (I.); D. Chemtob (D.); C. Balotta (Claudia); C. Mussini (C.); I. Caramma (I.); A. Capetti (A.); M.C. Colombo (M.); C. Rossi (Cesare); F. Prati (Francesco); F. Tramuto (F.); F. Vitale (F.); M. Ciccozzi (M.); G. Angarano (Guiseppe); G. Rezza (G.); R. Hemmer (R.); V. Arendt (V.); T. Staub (T.); F. Schneider (F.); F. Roman (Francois); C.A.B. Boucher (Charles); P.H.M. van Bentum (P. H M); K. Brinkman (Kees); E.L.M. Op de Coul (Eline); M.E. van der Ende (Marchina); I.M. Hoepelman (Ilja Mohandas); M.E.E. van Kasteren (Marjo); J. Juttmann (Job); M. Kuipers (M.); N. Langebeek (Nienke); C. Richter (C.); R.M.W.J. Santegoets (R. M W J); L. Schrijnders-Gudde (L.); R. Schuurman (Rob); B.J.M. van de Ven (B. J M); B. Asjö (Birgitta); V. Ormaasen (Vidar); P. Aavitsland (P.); J. Stanczak (J.); G.P. Stanczak (G.); E. Firlag-Burkacka (E.); A. Wiercinska-Drapalo (A.); E. Jablonowska (E.); E. Malolepsza (E.); M. Leszczyszyn-Pynka (M.); W. Szata (W.); A. de Palma (Andre); F. Borges (F.); T. Paix̃ao (T.); V. Duque (V.); F. Aráujo (F.); M. Stanojevic (Maja); D.J. Jevtovic (D.); D. Salemovic (D.); M. Habekova (M.); M. Mokras (M.); P. Truska (P.); M. Poljak (Mario); D.Z. Babic (Dunja); J. Tomazic (J.); S. Vidmar (Suzanna); P. Karner (P.); C. Gutíerrez (C.); C. deMendoza (C.); I. Erkicia (I.); P. Domingo (P.); X. Camino (X.); M.A. Galindo (Miguel Angel); J.L. Blanco (J.); M. Leal (M.); A. Masabeu (A.); A. Guelar (A.); J.M. Llibre (Josep M.); N. Margall (N.); C. Iribarren (Carlos); S. Gutierrez (S.); J.F. Baldov́i (J.); C.E. Pedreira (Carlos Eduardo); J.M. Gatell (J.); S. Moreno (S.); C. de Mendoza (Carmen); V. Soriano (Virtudes); A. Blaxhult (A.); A. Heidarian (A.); A. Karlsson (A.); K. Aperia-Peipke (K.); I.-M. Bergbrant (I.); M. Gissĺen (M.); M. Svennerholm (M.); P. Bj̈orkman (P.); G. Bratt (G.); M. Carlsson (M.); H. Ekvall (H.); M. Ericsson (M.); M. Ḧofer (M.); B. Johansson (Bert); N. Kuylenstierna (N.); K. Ljungberg (Karl); S. Mäkitalo (S.); A. Strand; K. Öberg (Kjell); T. Berg (Trine)

    2012-01-01

    textabstractBackground: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory

  11. Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Raquel Autran Coelho

    2004-03-01

    -RNA viral load in HIV-positive patients. METHODS: one hundred and fifteen HIV patients were evaluated retrospectively in the present study, during the period from January 2002 to April 2003, at a university hospital. Eighty-three patients presented cervical intraepithelial neoplasia (CIN in Pap smear, in comparison with thirty-two with no lesions. Patients were divided into three groups, according to CD4 counts: CD4 more than 500 cells/mm³, between 200 and 500 cells/mm³, and less than 200 cells/mm³, and other three groups, according to HIV viral load: less than 10,000 HIV-RNA copies/mL, between 10,000 and 100,000 HIV-RNA copies/mL, or more than 100,000 HIV-RNA copies/mL. Correlation was investigated by the Fisher test. RESULTS: of the eighty-three patients with CIN, 73% presented CD4 counts less than 500 cells/mm³. In all CD4 groups, more than 50% of the patients presented CIN. According to the viral load, 71.7% of the patients with less than 10,000 HIV-RNA copies/mL presented CIN I, compared with 11.3% that showed CIN III. In the group with higher viral load (>100.000 HIV-RNA copies/mL, 61.5% showed CIN I and 30.8% presented CIN III. CONCLUSION: association between viral load and CIN was established (p=0.013, which was not observed with CD4 cell counts and CIN. Concomitant cervicovaginal infection was considered a potential confounding factor.

  12. Pharyngitis - viral

    Science.gov (United States)

    ... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Pharyngitis - viral URL of this page: //medlineplus.gov/ency/article/ ...

  13. Viral gastroenteritis

    Science.gov (United States)

    ... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Viral gastroenteritis (stomach flu) URL of this page: //medlineplus. ...

  14. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2015-01-01

    In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...... with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18...

  15. Rapid detection and quantification of cell free cytomegalovirus by a high-speed centrifugation-based microculture assay: comparison to longitudinally analyzed viral DNA load and pp67 late transcript during lactation.

    Science.gov (United States)

    Hamprecht, Klaus; Witzel, Simone; Maschmann, Jens; Dietz, Klaus; Baumeister, Andrea; Mikeler, Elfriede; Goelz, Rangmar; Speer, Christian P; Jahn, Gerhard

    2003-12-01

    Human cytomegalovirus (HCMV) is reactivated in nearly every seropositive breastfeeding mother during lactation [Lancet 357 (2001) 513]. Conventional tissue culture (TC) and low-speed centrifugation-enhanced microtiter culture methods are not able to detect HCMV from milk during all stages of lactation. Development of a sensitive and quantitative microculture technique to describe the dynamics of HCMV reactivation in different milk compartments during lactation. Milk samples were collected longitudinally from seropositive breastfeeding mothers of preterm infants. Native milk samples were separated into fraction 1 (aqueous extract of milk fat), fraction 2 (cell and fat free milk whey) and fraction 3 (milk cells). Each of these fractions was screened qualitatively (TC, nPCR, pp67 late mRNA) and quantitatively (high-speed centrifugation-based microculture, quantitative PCR). Prior to low-speed centrifugation-enhanced inoculation, virus particles were concentrated by high-speed centrifugation (60 min at 50,000 x g, 4 degrees C). Using fraction 2 we were able to describe the dynamics of viral reactivation during lactation. We present the course of the quantitative virolactia and DNAlactia and qualitative detection of HCMV pp67 late mRNA in milk whey of four mothers (three transmitters and one non-transmitter). In all these cases virolactia described an unimodal and self limited course. Peak levels of virolactia for transmitters (T1: day 44; T2: day 43; T3: day 50) were closely related the onset of viruria of the corresponding preterm infants (U1: day 39; U2a/U2b: day 44/57; U3: day 60). The courses of viral load coincidence with the courses of DNA load. We present a rapid and highly sensitive microculture method for the quantification of cell free HCMV from milk whey and aqueous extracts from milk fat. Viral reactivation during lactation describes an unimodal course. Our findings have strong implications for quality control of any virus inactivation procedure.

  16. Enhanced sediment loading facilitates point bar growth and accelerates bank erosion along a modelled meander bend on the Sacramento River, USA

    Science.gov (United States)

    Ahmed, Joshua; Constantine, José A.; Hales, Tristram C.

    2017-04-01

    Meandering channels provide a conduit through which sediment and water is routed from the uplands to the sea. Alluvial material is periodically stored and transported through the channel network as permitted by the prevailing hydrologic conditions. In the lowlands, this sediment often accumulates as point bar deposits attached to the inner banks of meander bends; previous research has highlighted the importance of these bedforms in facilitating the link between in-stream sediment supplies and channel dynamism. We use a 2D curvilinear hydrodynamic model (MIKE 21C) to perform a number of experiments in which we alter the sediment load to investigate how changes in alluvial material fluxes affect the development of point bars and the resultant patterns of bank erosion. We reveal that increasing the sediment load by up to two times the normal causes the point bar to grow both longitudinally and transversely; concurrently, near-bank shear stresses are elevated resulting in accelerated rates of bank retreat compared to normal sediment loads. Our results suggest that enhanced sediment loads (potentially the result of changes in land use or climate) can trigger enhanced rates of bank erosion and channel change through the sequestration of alluvial material on point bars, which then deflect high-velocity fluid towards the outer bank of the meander. These results have implications for the development of morphodynamic meander models which should consider the role of topographic flow accelerations induced by the presence of point bars more explicitly. Moreover, increased boundary shear stresses accelerate rates of bank retreat and therefore control rates of riparian habitat development as well as exchanges of sediment and nutrients between the channel and floodplain.

  17. Comparison of the Load Deflection Characteristics of Esthetic and Metal Orthodontic Wires on Ceramic Brackets using Three Point Bending Test

    Directory of Open Access Journals (Sweden)

    Umal Hiralal Doshi

    2013-01-01

    Conclusion: Steel wires showed highest strength values, requiring the incorporation of loops and folds to reduce the load/deflection. NiTi and GFRPC wires produced more deflection at low levels of force, however the esthetic wire was shown to fracture and break.

  18. Altered EBV viral load setpoint after HIV seroconversion is in accordance with lack of predictive value of EBV load for the occurrence of AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    Piriou, Erwan R.; van Dort, Karel; Nanlohy, Nening M.; Miedema, Frank; van Oers, Marinus H.; van Baarle, Debbie

    2004-01-01

    In contrast to the situation in the post-transplant setting, in HIV-infected individuals an elevated EBV load is not predictive of EBV-related malignancies. To study whether a high EBV load is already a normal situation early in HIV infection and is not related to a decrease in immune function over

  19. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.

    Science.gov (United States)

    Morgan, Sophie B; Hemmink, Johanneke D; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E; Brookes, Sharon M; Bailey, Michael; Townsend, Alain M; Charleston, Bryan; Tchilian, Elma

    2016-06-15

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. Copyright © 2016 The Authors.

  20. Veterinary field test as screening tool for mastitis and HIV-1 viral load in breastmilk from HIV-infected Zambian women.

    Science.gov (United States)

    Dorosko, Stephanie M; Thea, Donald M; Saperstein, George; Russell, Robert M; Paape, Max J; Hinckley, Lynn S; Decker, William D; Semrau, Katherine; Sinkala, Moses; Kasonde, Prisca; Kankasa, Chipepo; Aldrovandi, Grace M; Hamer, Davidson H

    2007-09-01

    Clinical and subclinical mastitis increase the risk of mother-to-child transmission (MTCT) of HIV-1 through breastfeeding. We hypothesized that a field test for mastitis used for bovine milk, the California Mastitis Test, would detect high cell counts in milk of HIV-infected women. We also investigated whether total milk cell count would positively correlate with viral HIV-1 RNA in the milk of 128 HIV-positive Zambian women. Mean cell counts in each California Mastitis Test scoring category were significantly different (p < 0.01, n = 232). In a subset of 4-month postpartum milk samples tested for HIV-1 RNA, viral RNA levels did not significantly correlate with total cell count (r = 0.166, p = .244). The CMT may serve as a screening tool for mastitis in breastmilk, but total cell count does not correlate with HIV-1 RNA levels. Since both cell-free and cell-associated virus are associated with increased risk of MTCT, investigation of the relationship between total milk cell count and HIV-1 proviral DNA is warranted before a conclusive determination is made regarding use of the CMT as a clinical screening tool to detect cases at high risk for breastmilk transmission.

  1. Use of Salmon Cardiac Primary Cultures (SCPCs) of different genotypes for comparative kinetics of mx expression, viral load and ultrastructure pathology, after infection with Salmon Pancreas Disease Virus (SPDV).

    Science.gov (United States)

    Noguera, Patricia; Collet, Bertrand; Klinger, Matthias; Örün, Hristo; Del Pozo, Jorge

    2018-01-01

    In vitro fish based models have been extensively applied in human biomedical research but, paradoxically, less frequently in the research of fish health issues. Farmed Atlantic salmon can suffer from several viral conditions affecting the heart. Therefore, species-specific, cardiac in vitro models may represent a useful tool to help further understanding and management of these diseases. The mechanisms underlying genotype based resistance are complex and usually rely on a combined effect of elements from both the innate and adaptive immune response, which are further complicated by external environmental factors. Here we propose that Salmon Cardiac Primary Cultures (SCPCs) are a useful tool to investigate these mechanisms as the basis for genotypic differences between Atlantic salmon families in susceptibility to cardiotropic viral disease. Using SCPCs produced from two different commercially available Atlantic salmon embryonated ova (Atlantic Ova IPN sensitive" (S) and "Atlantic QTL-innOva ® IPN/PD" (R)), the influence of host genotype on the viral load and mx expression following Salmon Pancreas Disease Virus infection was assessed over a 15 day period. Both R and S SCPCs groups were successfully infected. A measurable difference between groups of viral nsP1 and host antiviral mx gene expression was observed (i.e. a later, but larger onset of mx expression in the R group). Mx expression peaks were followed by a decrease in viral nsP1 in both groups. Additionally, ultrastructural examination of infected SCPCs allowed the description of degenerative changes at the individual cell level. The SCPC model presents some advantages, over current fish cell culture monolayers and in vivo material, such as the presence of different cell components normally present in the target organ, as well as the removal of a layer of functional complexity (acquired immunity), making it possible to focus on tissue specific, early innate immune mechanisms. These preliminary results

  2. Herpes Simplex Virus 1 Mutant with Point Mutations in UL39 Is Impaired for Acute Viral Replication in Mice, Establishment of Latency, and Explant-Induced Reactivation.

    Science.gov (United States)

    Mostafa, Heba H; Thompson, Thornton W; Konen, Adam J; Haenchen, Steve D; Hilliard, Joshua G; Macdonald, Stuart J; Morrison, Lynda A; Davido, David J

    2018-04-01

    In the process of generating herpes simplex virus 1 (HSV-1) mutations in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in UL39 , which encodes the large subunit of ribonucleotide reductase, ICP6. These mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine (residue 950) substitutions in ICP6. To determine whether alteration of these amino acids was responsible for the KOS-NA phenotypes in vivo , we recombined the wild-type UL39 gene into the KOS-NA genome and rescued its acute replication phenotypes in mice. To further establish the role of UL39 in KOS-NA's decreased pathogenicity, the UL39 mutations were recombined into HSV-1 (generating UL39 mut ), and this mutant virus showed reduced ocular and TG replication in mice comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data suggest that amino acid 950 of ICP6 likely plays an important role in ICP6 accumulation and inhibition of apoptosis, consequently impairing HSV-1 pathogenesis in a mouse model of HSV-1 infection. IMPORTANCE HSV-1 is a major human pathogen that infects ∼80% of the human population and can be life threatening to infected neonates or immunocompromised individuals. Effective therapies for treatment of recurrent HSV-1 infections are limited, which emphasizes a critical need to understand in

  3. Enhanced sediment loading facilitates point bar growth and accelerates bank erosion along a modelled meander bend on the Sacramento River, USA

    Science.gov (United States)

    Ahmed, J.; Constantine, J. A.; Hales, T. C.

    2017-12-01

    Meandering channels provide a conduit through which sediment and water is routed from the uplands to the sea. Alluvial material is periodically stored and transported through the channel network as permitted by the prevailing hydrologic conditions. The lowlands are typically characterised by accumulations of sediment attached to the inner banks of meander bends (point bars). These bedforms have been identified as important for facilitating a link between in-stream sediment supplies and channel dynamism. A 2D curvilinear hydrodynamic model (MIKE 21C) was used to perform a number of experiments in which the sediment load was adjusted to investigate how changes in alluvial material fluxes affect the development of point bars and the resultant patterns of bank erosion. A doubling of the sediment load caused a longitudinal increase in the bar in the upstream direction and caused a coeval doubling of the transverse channel slope at the meander apex. The upstream growth of the point bar was accompanied by an increase in length over which lateral migration took place at the outer bank. The magnitude of outer bank erosion was 9-times greater for the high-sediment simulation. These results suggest that enhanced sediment loads (potentially the result of changes in land use or climate) can trigger greater rates of bank erosion and channel change through the sequestration of alluvial material on point bars, which encourage high-velocity fluid deflection towards the outer bank of the meander. This controls riparian habitat development and exchanges of sediment and nutrients across the channel-floodplain interface.

  4. [A cross-sectional study on the effect of virological response after HAART on subsets of T lymphocytes and expression of CD127 in pediatric AIDS patients with different viral loads].

    Science.gov (United States)

    Wu, Li-juan; Wu, Li-xiang; Bai, Shi

    2013-09-01

    To study the effect of HAART on subsets of T lymphocytes and expression of CD127 on memory and naїve CD4(+) and CD8(+)T cells in pediatric AIDS patients with different viral loads receiving HAART. A cross- sectional study on 194 pediatric AIDS patients receiving HAART was carried out and 52 age matched healthy children were recruited as controls. The percentage of CD4(+), CD8(+), CD8(+)CD45RA(+)CD127(+/-), CD8(+)CD45RO(+)CD127(+/-), CD4(+)CD45RA(+)CD127(+/-) and CD4(+)CD45RO(+)CD127(+/-)T cells was tested using flow cytometry, and HIV-RNA in plasma was detected by quantitative RT-PCR. The percentage of memory (CD45RO(+)) CD4(+)T cells decreased to (45.73 ± 8.85)%, and that of naїve (CD45RA(+)) CD4(+) and memory CD8(+)T increased to (60.44 ± 5.01)% and (54.69 ± 7.71) % respectively in the pediatric AIDS patients vs. controls (P memory CD4(+)CD127(+)T cells was (82.35 ± 2.31)%, which was higher than that of patients with VL ≥ 400 copies/ml, but lower than that of controls (P memory and naїve CD8(+)CD127(+)T cells was lower than that of controls (P AIDS patients is associated with viral load. Effective HAART can increase the percentage of naїve CD4(+)T cells and the life of memory CD4(+)T cells.

  5. A European multicientre study on the comparison of HBV viral loads between VERIS HBV assay and Roche COBAS® TAQMAN® HBV test, Abbott RealTime HBV assay, Siemens VERSANT HBV assay, and Qiagen artus HBV RG kit.

    Science.gov (United States)

    Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Izopet, Jacques; Lombardi, Alessandra; Marcos, MaAngeles; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-10-01

    Hepatitis B viral load testing is essential to treatment and monitoring decisions in patients with chronic Hepatitis B. Beckman Coulter has developed the VERIS HBV Assay (Veris) for use on the fully automated DxN VERIS Molecular Diagnostics System. 1 OBJECTIVES: To evaluate the clinical performance of the Veris HBV Assay at multiple EU laboratories STUDY DESIGN: Method comparison was performed with a total of 344 plasma specimens from HBV infected patients tested with Veris and COBAS ® TaqMan ® HBV Test (Cobas), 207 specimens tested with Veris and RealTime HBV Assay (RealTime), 86 specimens tested with Veris and VERSANT ® HBV Assay (Versant), and 74 specimens tested with Veris and artus ® HBV RG PCR kit (artus). Bland-Altman analysis showed average bias of -0.46 log 10 IU/mL between Veris and Cobas, -0.46 log 10 IU/mL between Veris and RealTime, -0.36 log 10 IU/mL between Veris and Versant, and -0.12 log 10 IU/mL between Veris and artus. Bias was consistent across the assay range. Patient monitoring results using Veris demonstrated similar viral load trends over time to Cobas, RealTime, and artus. The VERIS HBV Assay demonstrated comparable clinical performance, with varying degrees of negative bias, compared to other currently marketed assays for HBV DNA monitoring. This negative bias should be taken into consideration if switching monitoring methods to Veris. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  7. Higher viral load and genetic diversity of HIV-1 in seminal compartments than in blood of seven Chinese men who have sex with men and have early HIV-1 infection.

    Science.gov (United States)

    Jiao, Yan-Mei; Chen, Guang-Lei; Zhu, Wei-Jun; Huang, Hui-Huang; Fu, Jun-Liang; Chen, Wei-Wei; Shi, Ming; Zhang, Tong; Wu, Hao; Wang, Fu-Sheng

    2017-06-01

    To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  8. The estimation of the load of non-point source nitrogen and phosphorus based on observation experiments and export coefficient method in Three Gorges Reservoir Area

    Science.gov (United States)

    Tong, X. X.; Hu, B.; Xu, W. S.; Liu, J. G.; Zhang, P. C.

    2017-12-01

    In this paper, Three Gorges Reservoir Area (TGRA) was chosen to be the study area, the export coefficients of different land-use type were calculated through the observation experiments and literature consultation, and then the load of non-point source (NPS) nitrogen and phosphorus of different pollution sources such as farmland pollution sources, decentralized livestock and poultry breeding pollution sources and domestic pollution sources were estimated. The results show as follows: the pollution load of dry land is the main source of farmland pollution. The order of total nitrogen load of different pollution sources from high to low is livestock breeding pollution, domestic pollution, land use pollution, while the order of phosphorus load of different pollution sources from high to low is land use pollution, livestock breeding pollution, domestic pollution, Therefore, reasonable farmland management, effective control methods of dry land fertilization and sewage discharge of livestock breeding are the keys to the prevention and control of NPS nitrogen and phosphorus in TGRA.

  9. Processing of acoustic signals via wavelet & Choi - Williams analysis in three-point bending load of carbon/epoxy and glass/epoxy composites.

    Science.gov (United States)

    Beheshtizadeh, Nima; Mostafapour, Amir

    2017-08-01

    In this article, acoustic emission method was used for monitoring of flexural loading of GFRP (Glass fiber/epoxy composite) and CFRP (Carbon fiber/epoxy composite) via one acoustical sensor. In order to signal processing, various methods were employed such as wavelet transform, Short time Fourier transform, Choi - Williams transform and etc. Using two signal processing methods, wavelet transform and Choi - Williams transform, for monitoring of GFRP and CFRP specimens, determines strengths and weaknesses of each method and appointed the best analysis for signal processing of three point bending load of this type of composites. Based on information obtained from comparing of CFRP and GFRP, it is resulted that, the ratio of elastic modules and maximum load bearing of CFRP to GFRP is 1.36 and 3.25 respectively. Moreover, based on comparing of two analysis method results, Wavelet analysis was appointed better signal processing method for this type of load and material. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. New insights into the structure of the MHC class I peptide-loading complex and mechanisms of TAP inhibition by viral immune evasion proteins.

    Science.gov (United States)

    Praest, Patrique; Liaci, A Manuel; Förster, Friedrich; Wiertz, Emmanuel J H J

    2018-03-29

    Several hundred million years of co-evolution of vertebrates and invading pathogens have shaped the adaptive immune system to fight back the unwanted invaders through highly sophisticated defense mechanisms. Herpesviruses manage to dodge this immune response by hampering one of the central hinges of human adaptive immunity, the major histocompatibility complex (MHC) class I antigen presentation pathway. One of the bottlenecks of this pathway is the loading of pathogen-derived peptides onto MHC-I molecules in the endoplasmic reticulum (ER). This task is accomplished by the MHC class I peptide-loading complex (PLC), of which the transporter associated with antigen-processing (TAP) is a central component. In this review, we summarize recent structural and functional insights into the molecular architecture of the PLC, how TAP accomplishes the transport of peptides across the ER membrane, and how herpes- and poxviruses inhibit TAP-mediated peptide translocation and subsequent antigen presentation. Copyright © 2018. Published by Elsevier Ltd.

  11. Optimal Load-Tracking Operation of Grid-Connected Solid Oxide Fuel Cells through Set Point Scheduling and Combined L1-MPC Control

    Directory of Open Access Journals (Sweden)

    Siwei Han

    2018-03-01

    Full Text Available An optimal load-tracking operation strategy for a grid-connected tubular solid oxide fuel cell (SOFC is studied based on the steady-state analysis of the system thermodynamics and electrochemistry. Control of the SOFC is achieved by a two-level hierarchical control system. In the upper level, optimal setpoints of output voltage and the current corresponding to unit load demand is obtained through a nonlinear optimization by minimizing the SOFC’s internal power waste. In the lower level, a combined L1-MPC control strategy is designed to achieve fast set point tracking under system nonlinearities, while maintaining a constant fuel utilization factor. To prevent fuel starvation during the transient state resulting from the output power surging, a fuel flow constraint is imposed on the MPC with direct electron balance calculation. The proposed control schemes are testified on the grid-connected SOFC model.

  12. Mechanistic evaluation of the pros and cons of digital RT-LAMP for HIV-1 viral load quantification on a microfluidic device and improved efficiency via a two-step digital protocol.

    Science.gov (United States)

    Sun, Bing; Shen, Feng; McCalla, Stephanie E; Kreutz, Jason E; Karymov, Mikhail A; Ismagilov, Rustem F

    2013-02-05

    Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient's HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful

  13. No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010

    DEFF Research Database (Denmark)

    Helleberg, Marie; Kronborg, G; Larsen, Cs

    2013-01-01

    OBJECTIVES: Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark....... METHODS: We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/μL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from...... enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count...

  14. Could viral load combined with indirect serum markers be an option for predicting the degree of liver fibrosis in treatment-naïve chronic hepatitis B patients?

    Science.gov (United States)

    Afyon, Murat

    2017-02-01

    In a recent issue of the Revista Española de Enfermedades Digestivas, we read with interest the article by Coskun et al. "The diagnostic value of a globulin/platelet model for evaluating liver fibrosis in chronic hepatitis B patients". However, we wanted to emphasize some points about the article.

  15. Development and optimization of a sensitive TaqMan® real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load.

    Science.gov (United States)

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; de Figueiredo, Glauciane Garcia; Yamamoto, Aparecida Yulie; Mussi-Pinhata, Marisa Marcia; Kashima, Simone; Covas, Dimas Tadeu

    2016-09-01

    Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan® real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan® PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry-over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan® real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. [To consider negative viral loads below the limit of quantification can lead to errors in the diagnosis and treatment of hepatitis C virus infection].

    Science.gov (United States)

    Acero Fernández, Doroteo; Ferri Iglesias, María José; López Nuñez, Carme; Louvrie Freire, René; Aldeguer Manté, Xavier

    2013-01-01

    For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions. To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative. We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable» and those classified as «<1.50E+01IU/mL» (BLOQ). We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained. This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  17. A Seamless Handoff Scheme with Access Point Load Balance for Real-Time Services Support in 802.11 Wireless LANs

    Science.gov (United States)

    Manodham, Thavisak; Loyola, Luis; Miki, Tetsuya

    IEEE 802.11 wirelesses LANs (WLANs) have been rapidly deployed in enterprises, public areas, and households. Voice-over-IP (VoIP) and similar applications are now commonly used in mobile devices over wireless networks. Recent works have improved the quality of service (QoS) offering higher data rates to support various kinds of real-time applications. However, besides the need for higher data rates, seamless handoff and load balancing among APs are key issues that must be addressed in order to continue supporting real-time services across wireless LANs and providing fair services to all users. In this paper, we introduce a novel access point (AP) with two transceivers that improves network efficiency by supporting seamless handoff and traffic load balancing in a wireless network. In our proposed scheme, the novel AP uses the second transceiver to scan and find neighboring STAs in the transmission range and then sends the results to neighboring APs, which compare and analyze whether or not the STA should perform a handoff. The initial results from our simulations show that the novel AP module is more effective than the conventional scheme and a related work in terms of providing a handoff process with low latency and sharing traffic load with neighbor APs.

  18. Reduced Frequencies and Activation of Regulatory T Cells After the Treatment of HIV-1-Infected Individuals with the CCR5 Antagonist Maraviroc Are Associated with a Reduction in Viral Loads Rather Than a Direct Effect of the Drug on Regulatory T Cells.

    Science.gov (United States)

    Joedicke, Jara J; Dirks, Miriam; Esser, Stefan; Verheyen, Jens; Dittmer, Ulf

    2016-04-01

    Regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1 infection and they frequently express the chemokine receptor CCR5. We therefore investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc affected Tregs in chronically HIV-1-infected individuals. HIV-1-infected patients with high viral loads had elevated frequencies of activated Tregs in the peripheral blood compared with healthy controls. In patients successfully treated with antiretroviral drugs (undetectable viral loads), the frequency and the activation status of Tregs were comparable with healthy controls without any specific effect related to the treatment with Maraviroc. These results indicate that the control of viral replication in general rather than a direct binding of Maraviroc to CCR5-positive Tregs influences Treg responses in successfully treated chronically HIV-1-infected individuals.

  19. Application of modified export coefficient method on the load estimation of non-point source nitrogen and phosphorus pollution of soil and water loss in semiarid regions.

    Science.gov (United States)

    Wu, Lei; Gao, Jian-en; Ma, Xiao-yi; Li, Dan

    2015-07-01

    Chinese Loess Plateau is considered as one of the most serious soil loss regions in the world, its annual sediment output accounts for 90 % of the total sediment loads of the Yellow River, and most of the Loess Plateau has a very typical characteristic of "soil and water flow together", and water flow in this area performs with a high sand content. Serious soil loss results in nitrogen and phosphorus loss of soil. Special processes of water and soil in the Loess Plateau lead to the loss mechanisms of water, sediment, nitrogen, and phosphorus are different from each other, which are greatly different from other areas of China. In this study, the modified export coefficient method considering the rainfall erosivity factor was proposed to simulate and evaluate non-point source (NPS) nitrogen and phosphorus loss load caused by soil and water loss in the Yanhe River basin of the hilly and gully area, Loess Plateau. The results indicate that (1) compared with the traditional export coefficient method, annual differences of NPS total nitrogen (TN) and total phosphorus (TP) load after considering the rainfall erosivity factor are obvious; it is more in line with the general law of NPS pollution formation in a watershed, and it can reflect the annual variability of NPS pollution more accurately. (2) Under the traditional and modified conditions, annual changes of NPS TN and TP load in four counties (districts) took on the similar trends from 1999 to 2008; the load emission intensity not only is closely related to rainfall intensity but also to the regional distribution of land use and other pollution sources. (3) The output structure, source composition, and contribution rate of NPS pollution load under the modified method are basically the same with the traditional method. The average output structure of TN from land use and rural life is about 66.5 and 17.1 %, the TP is about 53.8 and 32.7 %; the maximum source composition of TN (59 %) is farmland; the maximum source

  20. Reduction in HIV community viral loads following the implementation of a "Treatment as Prevention" strategy over 2 years at a population-level among men who have sex with men in Hangzhou, China.

    Science.gov (United States)

    He, Lin; Yang, Jiezhe; Ma, Qiaoqin; Zhang, Jiafeng; Xu, Yun; Xia, Yan; Chen, Wanjun; Wang, Hui; Zheng, Jinlei; Jiang, Jun; Luo, Yan; Xu, Ke; Zhang, Xingliang; Xia, Shichang; Pan, Xiaohong

    2018-02-01

    Previous studies have shown that the increased coverage of antiretroviral therapy (ART) could reduce the community viral load (CVL) and reduce the occurrence of new HIV infections. However, the impact on the reduction of HIV transmission among men who have sex with men (MSM) is much less certain. The frequency of HIV infections in MSM have been rapidly increasing in recent years in Hangzhou, China. The "Treatment as Prevention" strategy was implemented at a population-level for HIV-infected MSM from January 2014 to June 2016 in Hangzhou; it aimed to increase the ART coverage, reduce the CVL, and reduce HIV transmission. We investigated a subset of MSM diagnosed with HIV pre- and post-implementation of the strategy, using random sampling methods. Viral load (VL) testing was performed for all enrolled individuals; the lower limits of detection were 20 and 50 copies/mL. The data on infections were collected from the national epidemiology database of Hangzhou. Logistic regression analyses were conducted to identify factors associated with the differences in social demographic characteristics and available VL data. The ART coverage increased from 60.7% (839/1383) during the pre-implementation period to 92.3% (2183/2365) during the post-implementation period in Hangzhou. A total of 940 HIV-infected MSM were selected for inclusion in this study: 490 (52.1%) and 450 (47.9%) MSM in the pre- and post-implementation periods, respectively. In total, 89.5% (841/940) of patients had data available on VL rates. The mean CVL was 579 copies/mL pre-implementation and this decreased to 33 copies/mL post-implementation (Kruskal-Wallis < 0.001). The mean CVL decreased for all variables investigated post-implementation of the treatment strategy (P < 0.05). The undetectable VL (≤400 copies/mL) rate pre-implementation period was 50.0% which increased to 84.7% post-implementation (P < 0.001). The mean CVL at the county level significantly decreased in each county post

  1. CXCR5+ CD8+ T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection.

    Science.gov (United States)

    Jiang, Hang; Li, Linhai; Han, Jiang; Sun, Zhiwei; Rong, Yihui; Jin, Yun

    2017-04-01

    Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5 + CD8 + T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5 + CD8 + T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5 + CD8 + T cells in peripheral blood, in which CXCR5 + CD8 + T cells were negatively correlated with the frequency of CXCR5 + CD4 + T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5 + CD8 + T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5 - CD8 + T cells. Unlike CXCR5 + CD4 + T cells, when incubated with naive CD19 + CD27 - B cells, CXCR5 + CD8 + T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5 + CD8 + T cells in B cell-CXCR5 + CD4 + T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5 + CD8 + T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5 + CD8 + T cells tended to associate with low HBV DNA load, and the frequency of CXCR5 + CD8 + T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5 + CD8 + T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.

  2. Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection

    Science.gov (United States)

    Radebe, Mopo; Gounder, Kamini; Mokgoro, Mammekwa; Ndhlovu, Zaza M.; Mncube, Zenele; Mkhize, Lungile; van der Stok, Mary; Jaggernath, Manjeetha; Walker, Bruce D.; Ndung’u, Thumbi

    2015-01-01

    Objective We characterized protein-specific CD8+ T-cell immunodominance patterns during the first year of HIV-1 infection, and their impact on viral evolution and immune control. Methods We analyzed CD8+ T-cell responses to the full HIV-1 proteome during the first year of infection in eighteen antiretroviral-naïve individuals with acute HIV-1 subtype C infection, all identified prior to seroconversion. Ex vivo and cultured IFN-γ ELISPOT assays were performed and viruses from plasma were sequenced within defined CTL Gag epitopes. Results Nef-specific CD8+ T-cell responses were dominant during the first 4 weeks post infection and made up 40% of total responses at this time, yet by 1 year responses against this region had declined and Gag responses made up to 47% of all T-cell responses measured. An inverse correlation between the breadth of Gag-specific responses and viral load set point was evident at 26 weeks post infection (p=0.0081; r= −0.60) and beyond. An inverse correlation between the number of persistent responses targeting Gag and viral set point was also identified (p=0.01; r=−0.58). Gag-specific responses detectable by the cultured ELISPOT assay correlated negatively with viral load set point (p=0.0013; r=−0.91). Sequence evolution in targeted and non-targeted Gag epitopes in this cohort was infrequent. Conclusions These data underscore the importance of HIV-specific CD8+ T-cell responses, particularly to the Gag protein, in the maintenance of low viral load levels during primary infection and show that these responses are initially poorly elicited by natural infection. These data have implications for vaccine design strategies. PMID:25387316

  3. Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.

    Science.gov (United States)

    Camargo, Jose F; Kulkarni, Hemant; Agan, Brian K; Gaitan, Alvaro A; Beachy, Lisa A; Srinivas, Sowmya; He, Weijing; Anderson, Stephanie; Marconi, Vincent C; Dolan, Matthew J; Ahuja, Sunil K

    2009-06-15

    Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis. The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects. The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness. Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.

  4. Particle swarm approach based on quantum mechanics and harmonic oscillator potential well for economic load dispatch with valve-point effects

    Energy Technology Data Exchange (ETDEWEB)

    dos Santos Coelho, Leandro [Pontifical Catholic University of Parana, PUCPR Industrial and Systems Engineering Graduate Program, PPGEPS, Imaculada Conceicao, 1155, Zip code 80215-901, Curitiba, PR (Brazil); Mariani, Viviana Cocco [Pontifical Catholic University of Parana, PUCPR Mechanical Engineering Graduate Program, PPGEM, Imaculada Conceicao, 1155, Zip code 80215-901, Curitiba, PR (Brazil)

    2008-11-15

    Particle swarm optimization (PSO) algorithm is population-based heuristic global search algorithm inspired by social behavior patterns of organisms that live and interact within large groups. The PSO is based on researches on swarms such as fish schooling and bird flocking. Inspired by the classical PSO method and quantum mechanics theories, this work presents a quantum-inspired version of the PSO (QPSO) using the harmonic oscillator potential well (HQPSO) to solve economic dispatch problems. A 13-units test system with incremental fuel cost function that takes into account the valve-point loading effects is used to illustrate the effectiveness of the proposed HQPSO method compared with the simulation results based on the classical PSO, the QPSO, and other optimization algorithms reported in the literature. (author)

  5. Particle swarm approach based on quantum mechanics and harmonic oscillator potential well for economic load dispatch with valve-point effects

    Energy Technology Data Exchange (ETDEWEB)

    Santos Coelho, Leandro dos [Pontifical Catholic University of Parana, PUCPR Industrial and Systems Engineering Graduate Program, PPGEPS, Imaculada Conceicao, 1155, Zip code 80215-901, Curitiba, PR (Brazil)], E-mail: leandro.coelho@pucpr.br; Mariani, Viviana Cocco [Pontifical Catholic University of Parana, PUCPR Mechanical Engineering Graduate Program, PPGEM, Imaculada Conceicao, 1155, Zip code 80215-901, Curitiba, PR (Brazil)], E-mail: viviana.mariani@pucpr.br

    2008-11-15

    Particle swarm optimization (PSO) algorithm is population-based heuristic global search algorithm inspired by social behavior patterns of organisms that live and interact within large groups. The PSO is based on researches on swarms such as fish schooling and bird flocking. Inspired by the classical PSO method and quantum mechanics theories, this work presents a quantum-inspired version of the PSO (QPSO) using the harmonic oscillator potential well (HQPSO) to solve economic dispatch problems. A 13-units test system with incremental fuel cost function that takes into account the valve-point loading effects is used to illustrate the effectiveness of the proposed HQPSO method compared with the simulation results based on the classical PSO, the QPSO, and other optimization algorithms reported in the literature.

  6. Sleeve gastrectomy is a safe and efficient procedure in HIV patients with morbid obesity: a case series with results in weight loss, comorbidity evolution, CD4 count, and viral load.

    Science.gov (United States)

    Fysekidis, Marinos; Cohen, Régis; Bekheit, Mohamed; Chebib, Joseph; Boussairi, Abdelghani; Bihan, Hélène; Khuong, Marie Aude; Finkielsztejn, Laurent; Mendoza, Gabriela; Abgrall, Sophie; Condé, Djiba; Catheline, Jean Marc

    2015-02-01

    The efficacy and safety of bariatric surgery have been poorly studied in patients affected with HIV. Although sleeve gastrectomy (SG) is the most widely used procedure in many countries, most of the published literature reported results with the gastric bypass (GBP) procedure on morbidly obese HIV patients. We have evaluated retrospectively, in eight consecutive patients who underwent a SG, its effect in weight loss and its impact on the treatment and on the markers of HIV infection. Seven out of eight patients were females. The mean age was 46 years, with a median preoperative BMI of 42 kg/m(2). The mean duration of HIV infection and CD4 cell count were 13.4 years and 457 cells/mm(3), respectively. The mean weight loss was 37 kg in 20 months, the excess BMI loss was 80.8 ± 30.9 %, and the excess weight loss is 81.5 ± 28.9 % with one minor complication. CD4 counts were unchanged. Three patients had therapy modifications that were unrelated to bariatric surgery. Two patients had a therapeutic drug monitoring before and after the intervention. Plasma concentrations remained in therapeutic levels after the SG. Most comorbidities disappeared postoperatively, decreasing the cardiovascular risk. The sleeve gastrectomy was safe and effective with no consequences on CD4 counts and viral load in HIV-affected obese patients. It should be considered as a part of the treatment in morbidly obese HIV patients.

  7. Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16⁺ NK cell-like phenotype and correlates with HIV viral load.

    Science.gov (United States)

    Hong, Henoch S; Ahmad, Fareed; Eberhard, Johanna M; Bhatnagar, Nupur; Bollmann, Benjamin A; Keudel, Phillip; Ballmaier, Matthias; Zielinska-Skowronek, Margot; Schmidt, Reinhold E; Meyer-Olson, Dirk

    2012-01-01

    NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56(dim)CD16⁺ and CD56⁻CD16⁺ NK cells. However, the impact of HIV-infection on CD56(bright) NK cells is less well understood. Here we report a rise of CD56(bright) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7⁻CD56(bright) NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56(dim)CD16⁺ NK cells. Furthermore, CD56(bright) NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56(bright) NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.

  8. A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

    Science.gov (United States)

    Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-07-01

    Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  10. Qualidade de vida de portadores de HIV/AIDS e sua relação com linfócitos CD4+, carga viral e tempo de diagnóstico Quality of life of people living with HIV/AIDS and its relationship with CD4+ lymphocytes, viral load and time of diagnosis

    Directory of Open Access Journals (Sweden)

    Brunno Elias Ferreira

    2012-03-01

    Full Text Available A qualidade de vida (QV acompanha o tratamento dos pacientes com AIDS, juntamente com as inovações farmacológicas, que permitiram prolongar a vida do paciente e a manutenção de seu bem-estar. O presente estudo objetivou verificar a QV desses pacientes e correlacionar com dados clínicos e laboratoriais. Participaram 205 pacientes HIV/AIDS, os quais responderam ao questionário WHOQOL-120-HIV e tiveram coletados seus dados sociodemográficos, clínicos e laboratoriais. A média etária foi de 40,59 ± 11,81 anos; contagem de linfócitos CD4+ de 397,97 ± 232,84 mm³ e 5,23 ± 3,94 anos de diagnóstico do HIV. A carga viral era Quality of life (QOL has accompanied the treatment of AIDS patients, along with pharmacological innovations that have allowed patients to live longer and maintain their well-being. The present study aimed at evaluating the QOL of these patients and correlate it with clinical and laboratory data. The study included 205 patients with HIV/AIDS, who answered the WHOQOL-120-HIV; and whose socio-demographic data, clinical and laboratory findings were collected. The average age was 40.59 ± 11.81 years; CD4+ lymphocyte count, 397.9 ± 232.84 mm³; and years of diagnosis of HIV, 5.23 ± 3.94. Viral load was <50 copies/ml in 115 patients; 50 to 10.000 in 61; and above 10.000 copies in 29 patients. Domains achieved satisfactory average scores, and the best were the psychological (14.5 ± 2.7, followed by social relationships (13.7 ± 2.2, physical (12.7 ± 3.5, independence (12.6 ± 2.5, personal beliefs (12.4 ± 2.4, and environment (12.4 ± 1.8. The best scores on pain, pleasure, social support, physical environment, and personal belief facets were observed for those with higher CD4 levels (p < 0.05. The best scores for the finance, leisure, concerns about the future, overall QOL, and perceived health facets were observed for patients with viral load <50 (p < 0.05. The highest rates for energy, fatigue, sexual activity

  11. Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies.

    Directory of Open Access Journals (Sweden)

    Brian J Willett

    Full Text Available Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV, a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1 or diverse (Group 2 challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

  12. Analysis of hepatitis C viral dynamics using Latin hypercube sampling

    Science.gov (United States)

    Pachpute, Gaurav; Chakrabarty, Siddhartha P.

    2012-12-01

    We consider a mathematical model comprising four coupled ordinary differential equations (ODEs) to study hepatitis C viral dynamics. The model includes the efficacies of a combination therapy of interferon and ribavirin. There are two main objectives of this paper. The first one is to approximate the percentage of cases in which there is a viral clearance in absence of treatment as well as percentage of response to treatment for various efficacy levels. The other is to better understand and identify the parameters that play a key role in the decline of viral load and can be estimated in a clinical setting. A condition for the stability of the uninfected and the infected steady states is presented. A large number of sample points for the model parameters (which are physiologically feasible) are generated using Latin hypercube sampling. An analysis of the simulated values identifies that, approximately 29.85% cases result in clearance of the virus during the early phase of the infection. Results from the χ2 and the Spearman's tests done on the samples, indicate a distinctly different distribution for certain parameters for the cases exhibiting viral clearance under the combination therapy.

  13. Non-Disclosure of HIV Status and Associations with Psychological Factors, ART Non-Adherence, and Viral Load Non-Suppression Among People Living with HIV in the UK.

    Science.gov (United States)

    Daskalopoulou, Marina; Lampe, Fiona C; Sherr, Lorraine; Phillips, Andrew N; Johnson, Margaret A; Gilson, Richard; Perry, Nicky; Wilkins, Ed; Lascar, Monica; Collins, Simon; Hart, Graham; Speakman, Andrew; Rodger, Alison J

    2017-01-01

    Disclosure of HIV status to family, friends, and a stable partner may be linked to improved health outcomes for people living with HIV. This study assessed whether non-disclosure is associated with psychological symptoms, non-adherence to antiretroviral therapy (ART), and viral load (VL) non-suppression. A total of 3258 HIV-diagnosed individuals in the UK completed the confidential ASTRA study questionnaire (2011-2012). Participants reported whether they told anyone they had HIV; to which confidant(s) (friends, family, work colleagues, stable partner) and to what extent (none, some, most/all). The prevalence and factors associated with non-disclosure were assessed. Associations between non-disclosure and the following factors were established using modified Poisson regression with adjustment for socio-demographic factors (gender, age group, ethnicity), HIV-related factors (time since HIV diagnosis, ART status), and clinic: low social support (score ≤ 12 on modified Duke-UNC FSSQ); depression and anxiety symptoms (≥10 on PHQ-9 and GAD-7 respectively); self-reported ART non-adherence in past 2 weeks/3 months; VL non-suppression (clinic-recorded VL > 50 copies/mL among those who started ART ≥ 6 months ago). Among 3233 participants with disclosure data, the prevalence of non-disclosure to anyone was 16.6 % (n/N = 61/367) among heterosexual men, 15.7 % (98/626) among women, and 5.0 % (113/2240) among MSM. MSM were more likely to disclose to some/all friends compared to family (85.8 vs. 59.9 %) while heterosexuals were less likely to disclose to friends than family (44.1 vs. 61.1 % for men, 57.5 vs. 67.1 % for women). Among 1,631 participants with a stable partner, non-disclosure to a stable partner was 4.9 % for MSM, 10.9 % for heterosexual men, and 13.0 % for women. In adjusted analyses, older age (≥60 years), non-white ethnicity, more recent HIV diagnosis, and not having a stable partner were significantly associated with overall non

  14. Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

    Science.gov (United States)

    Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

    2016-07-01

    Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.

  15. A significant reduction in the frequency of HIV-1 drug resistance in Québec from 2001 to 2011 is associated with a decrease in the monitored viral load.

    Directory of Open Access Journals (Sweden)

    Hugues Charest

    Full Text Available BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL in treatment-naïve (TN and treatment-experienced (TE individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%], nucleoside [NRTI (from 78% to 37% and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004. CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant

  16. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  17. Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

    Science.gov (United States)

    Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

    2016-11-01

    Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

  18. Association of CD4+ T-cell Count, HIV-1 RNA Viral Load, and Antiretroviral Therapy With Kaposi Sarcoma Risk Among HIV-infected Persons in the United States and Canada.

    Science.gov (United States)

    Dubrow, Robert; Qin, Li; Lin, Haiqun; Hernández-Ramírez, Raúl U; Neugebauer, Romain S; Leyden, Wendy; Althoff, Keri N; Achenbach, Chad J; Hessol, Nancy A; Modur, Sharada P; DʼSouza, Gypsyamber; Bosch, Ronald J; Grover, Surbhi; Horberg, Michael A; Kitahata, Mari M; Mayor, Angel M; Novak, Richard M; Rabkin, Charles S; Sterling, Timothy R; Goedert, James J; Justice, Amy C; Engels, Eric A; Moore, Richard D; Silverberg, Michael J

    2017-08-01

    Kaposi sarcoma (KS) remains common among HIV-infected persons. To better understand KS etiology and to help target prevention efforts, we comprehensively examined a variety of CD4 T-cell count and HIV-1 RNA viral load (VL) measures, as well as antiretroviral therapy (ART) use, to determine independent predictors of KS risk. North American AIDS Cohort Collaboration on Research and Design. We followed HIV-infected persons during 1996-2009 from 18 cohorts. We used time-updated Cox regression to model relationships between KS risk and recent, lagged, trajectory, and cumulative CD4 count or VL measures, as well as ART use. We used Akaike's information criterion and global P values to derive a final model. In separate models, the relationship between each measure and KS risk was highly significant (P < 0.0001). Our final mutually adjusted model included recent CD4 count [hazard ratio (HR) for <50 vs. ≥500 cells/μL = 12.4; 95% confidence interval (CI): 6.5 to 23.8], recent VL (HR for ≥100,000 vs. ≤500 copies/mL = 3.8; 95% CI: 2.0 to 7.3), and cumulative (time-weighted mean) VL (HR for ≥100,000 vs. ≤500 copies/mL = 2.5; 95% CI: 1.0 to 5.9). Each P-trend was <0.0001. After adjusting for these measures, we did not detect an independent association between ART use and KS risk. Our results suggested a multifactorial etiology for KS, with early and late phases of development. The cumulative VL effect suggested that controlling HIV replication promptly after HIV diagnosis is important for KS prevention. We observed no evidence for direct anti-KS activity of ART, independent of CD4 count and VL.

  19. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

    Science.gov (United States)

    Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

    2016-01-01

    WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public sector. This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

  20. Validation of dilution of plasma samples with phosphate buffered saline to eliminate the problem of small volumes associated with children infected with HIV-1 for viral load testing using Cobas AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0 (CAP CTM HIV v2.0).

    Science.gov (United States)

    Mine, Madisa; Nkoane, Tapologo; Sebetso, Gaseene; Sakyi, Bright; Makhaola, Kgomotso; Gaolathe, Tendani

    2013-12-01

    The sample requirement of 1 mL for the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0 (CAP CTM HIV v2.0) limits its utility in measuring plasma HIV-1 RNA levels for small volume samples from children infected with HIV-1. Viral load monitoring is the standard of care for HIV-1-infected patients on antiretroviral therapy in Botswana. The study aimed to validate the dilution of small volume samples with phosphate buffered saline (1× PBS) when quantifying HIV-1 RNA in patient plasma. HIV RNA concentrations were determined in undiluted and diluted pairs of samples comprising panels of quality assessment standards (n=52) as well as patient samples (n=325). There was strong correlation (R(2)) of 0.98 and 0.95 within the dynamic range of the CAP CTM HIV v2.0 test between undiluted and diluted samples from quality assessment standards and patients, respectively. The difference between viral load measurements of diluted and undiluted pairs of quality assessment standards and patient samples using the Altman-Bland test showed that the 95% limits of agreement were between -0.40 Log 10 and 0.49 Log 10. This difference was within the 0.5 Log 10 which is generally considered as normal assay variation of plasma RNA levels. Dilution of samples with 1× PBS produced comparable viral load measurements to undiluted samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Non-Point Source Pollutant Load Variation in Rapid Urbanization Areas by Remote Sensing, Gis and the L-THIA Model: A Case in Bao'an District, Shenzhen, China

    Science.gov (United States)

    Li, Tianhong; Bai, Fengjiao; Han, Peng; Zhang, Yuanyan

    2016-11-01

    Urban sprawl is a major driving force that alters local and regional hydrology and increases non-point source pollution. Using the Bao'an District in Shenzhen, China, a typical rapid urbanization area, as the study area and land-use change maps from 1988 to 2014 that were obtained by remote sensing, the contributions of different land-use types to NPS pollutant production were assessed with a localized long-term hydrologic impact assessment (L-THIA) model. The results show that the non-point source pollution load changed significantly both in terms of magnitude and spatial distribution. The loads of chemical oxygen demand, total suspended substances, total nitrogen and total phosphorus were affected by the interactions between event mean concentration and the magnitude of changes in land-use acreages and the spatial distribution. From 1988 to 2014, the loads of chemical oxygen demand, suspended substances and total phosphorus showed clearly increasing trends with rates of 132.48 %, 32.52 % and 38.76 %, respectively, while the load of total nitrogen decreased by 71.52 %. The immigrant population ratio was selected as an indicator to represent the level of rapid urbanization and industrialization in the study area, and a comparison analysis of the indicator with the four non-point source loads demonstrated that the chemical oxygen demand, total phosphorus and total nitrogen loads are linearly related to the immigrant population ratio. The results provide useful information for environmental improvement and city management in the study area.

  2. Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

    OpenAIRE

    Pratheek, B. M.; Saha, Soham; Maiti, Prasanta K.; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2013-01-01

    The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell resp...

  3. СRACK-RESISTANCE AND DURABILITY OF NUCLEAR-POWER STATION (NPS) LOAD-CARRYING STRUCTURES FROM FRACTURE MECHANICS POINT OF VIEW

    OpenAIRE

    S. N. Leonovich

    2009-01-01

    The paper presents calculations pertaining to survivability of NPS load-carrying elements with respect to crack-resistance. These calculations reflect their resistance ability to actions of mechanical, thermal, hydro-dynamic, electro-magnetic  loads in the case when there are defects in the elements (initially technological defects or operational ones). The most dangerous defects are micro- and macro-cracks that create maximum high concentration of stresses and deformations.

  4. Non-Point Source Pollutant Load Variation in Rapid Urbanization Areas by Remote Sensing, Gis and the L-THIA Model: A Case in Bao'an District, Shenzhen, China.

    Science.gov (United States)

    Li, Tianhong; Bai, Fengjiao; Han, Peng; Zhang, Yuanyan

    2016-11-01

    Urban sprawl is a major driving force that alters local and regional hydrology and increases non-point source pollution. Using the Bao'an District in Shenzhen, China, a typical rapid urbanization area, as the study area and land-use change maps from 1988 to 2014 that were obtained by remote sensing, the contributions of different land-use types to NPS pollutant production were assessed with a localized long-term hydrologic impact assessment (L-THIA) model. The results show that the non-point source pollution load changed significantly both in terms of magnitude and spatial distribution. The loads of chemical oxygen demand, total suspended substances, total nitrogen and total phosphorus were affected by the interactions between event mean concentration and the magnitude of changes in land-use acreages and the spatial distribution. From 1988 to 2014, the loads of chemical oxygen demand, suspended substances and total phosphorus showed clearly increasing trends with rates of 132.48 %, 32.52 % and 38.76 %, respectively, while the load of total nitrogen decreased by 71.52 %. The immigrant population ratio was selected as an indicator to represent the level of rapid urbanization and industrialization in the study area, and a comparison analysis of the indicator with the four non-point source loads demonstrated that the chemical oxygen demand, total phosphorus and total nitrogen loads are linearly related to the immigrant population ratio. The results provide useful information for environmental improvement and city management in the study area.

  5. Core Gene Expression and Association of Genotypes with Viral ...

    African Journals Online (AJOL)

    HP

    Purpose: To determine genotypic distribution, ribonucleic acid (RNA) RNA viral load and express core gene from Hepatitis C Virus (HCV) infected patients in Punjab, Pakistan. Methods: A total of 1690 HCV RNA positive patients were included in the study. HCV genotyping was tested by type-specific genotyping assay, viral ...

  6. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  7. Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type H5N1 influenza challenge and controls viral loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.

    Science.gov (United States)

    Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J; Carter, Donald M; Ross, Ted M; Khurana, Surender; Golding, Hana

    2012-11-01

    Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.

  8. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  9. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic

  10. Evaluation of Land Use, Land Management and Soil Conservation Strategies to Reduce Non-Point Source Pollution Loads in the Three Gorges Region, China.

    Science.gov (United States)

    Strehmel, Alexander; Schmalz, Britta; Fohrer, Nicola

    2016-11-01

    The construction of the Three Gorges Dam in China and the subsequent impoundment of the Yangtze River have induced a major land use change in the Three Gorges Reservoir Region, which fosters increased inputs of sediment and nutrients from diffuse sources into the water bodies. Several government programs have been implemented to mitigate high sediment and nutrient loads to the reservoir. However, institutional weaknesses and a focus on economic development have so far widely counteracted the effectiveness of these programs. In this study, the eco-hydrological model soil and water assessment tool is used to assess the effects of changes in fertilizer amounts and the conditions of bench terraces in the Xiangxi catchment in the Three Gorges Reservoir Region on diffuse matter releases. With this, the study aims at identifying efficient management measures, which should have priority. The results show that a reduction of fertilizer amounts cannot reduce phosphorus loads considerably without inhibiting crop productivity. The condition of terraces in the catchment has a strong impact on soil erosion and phosphorus releases from agricultural areas. Hence, if economically feasible, programmes focusing on the construction and maintenance of terraces in the region should be implemented. Additionally, intercropping on corn fields as well as more efficient fertilization schemes for agricultural land were identified as potential instruments to reduce diffuse matter loads further. While the study was carried out in the Three Gorges Region, its findings may also beneficial for the reduction of water pollution in other mountainous areas with strong agricultural use.

  11. Evaluation of Land Use, Land Management and Soil Conservation Strategies to Reduce Non-Point Source Pollution Loads in the Three Gorges Region, China

    Science.gov (United States)

    Strehmel, Alexander; Schmalz, Britta; Fohrer, Nicola

    2016-11-01

    The construction of the Three Gorges Dam in China and the subsequent impoundment of the Yangtze River have induced a major land use change in the Three Gorges Reservoir Region, which fosters increased inputs of sediment and nutrients from diffuse sources into the water bodies. Several government programs have been implemented to mitigate high sediment and nutrient loads to the reservoir. However, institutional weaknesses and a focus on economic development have so far widely counteracted the effectiveness of these programs. In this study, the eco-hydrological model soil and water assessment tool is used to assess the effects of changes in fertilizer amounts and the conditions of bench terraces in the Xiangxi catchment in the Three Gorges Reservoir Region on diffuse matter releases. With this, the study aims at identifying efficient management measures, which should have priority. The results show that a reduction of fertilizer amounts cannot reduce phosphorus loads considerably without inhibiting crop productivity. The condition of terraces in the catchment has a strong impact on soil erosion and phosphorus releases from agricultural areas. Hence, if economically feasible, programmes focusing on the construction and maintenance of terraces in the region should be implemented. Additionally, intercropping on corn fields as well as more efficient fertilization schemes for agricultural land were identified as potential instruments to reduce diffuse matter loads further. While the study was carried out in the Three Gorges Region, its findings may also beneficial for the reduction of water pollution in other mountainous areas with strong agricultural use.

  12. Discovering hidden viral piracy.

    Science.gov (United States)

    Kim, Eddo; Kliger, Yossef

    2005-12-01

    Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.

  13. Studies on the Effects of High Renewable Penetrations on Driving Point Impedance and Voltage Regulator Performance: National Renewable Energy Laboratory/Sacramento Municipal Utility District Load Tap Changer Driving Point Impedance Project

    Energy Technology Data Exchange (ETDEWEB)

    Nagarajan, Adarsh [National Renewable Energy Lab. (NREL), Golden, CO (United States); Coddington, Michael H. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Brown, David [Sacramento Municipal Utility District, CA (United States); Hassan, Sheikh [Sacramento Municipal Utility District, CA (United States); Franciosa, Leonardo [Sacramento Municipal Utility District, CA (United States); Sison-Lebrilla, Elaine [Sacramento Municipal Utility District, CA (United States)

    2018-01-09

    Voltage regulators perform as desired when regulating from the source to the load and when regulating from a strong source (utility) to a weak source (distributed generation). (See the glossary for definitions of a strong source and weak source.) Even when the control is provisioned for reverse operation, it has been observed that tap-changing voltage regulators do not perform as desired in reverse when attempting regulation from the weak source to the strong source. The region of performance that is not as well understood is the regulation between sources that are approaching equal strength. As part of this study, we explored all three scenarios: regulator control from a strong source to a weak source (classic case), control from a weak source to a strong source (during reverse power flow), and control between equivalent sources.

  14. Hepatitis viral aguda

    OpenAIRE

    Héctor Rubén Hernández Garcés; René F. Espinosa Álvarez

    1998-01-01

    Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, ...

  15. Viral Gastroenteritis (Stomach Flu)

    Science.gov (United States)

    ... Viral gastroenteritis (stomach flu) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  16. Hepatitis viral aguda

    Directory of Open Access Journals (Sweden)

    Héctor Rubén Hernández Garcés

    1998-10-01

    Full Text Available Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, and the complementary examinations with special emphasis on the viral markers and the positive diagnosis were also considered

  17. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  18. Controlling viral outbreaks: Quantitative strategies.

    Science.gov (United States)

    Mummert, Anna; Weiss, Howard

    2017-01-01

    Preparing for and responding to outbreaks of serious livestock infectious diseases are critical measures to safeguard animal health, public health, and food supply. Almost all of the current control strategies are empirical, and mass culling or "stamping out" is frequently the principal strategy for controlling epidemics. However, there are ethical, ecological, and economic reasons to consider less drastic control strategies. Here we use modeling to quantitatively study the efficacy of different control measures for viral outbreaks, where the infectiousness, transmissibility and death rate of animals commonly depends on their viral load. We develop a broad theoretical framework for exploring and understanding this heterogeneity. The model includes both direct transmission from infectious animals and indirect transmission from an environmental reservoir. We then incorporate a large variety of control measures, including vaccination, antivirals, isolation, environmental disinfection, and several forms of culling, which may result in fewer culled animals. We provide explicit formulae for the basic reproduction number, R0, for each intervention and for combinations. We evaluate the control methods for a realistic simulated outbreak of low pathogenic avian influenza on a mid-sized turkey farm. In this simulated outbreak, culling results in more total dead birds and dramatically more when culling all of the infected birds.

  19. Recombination-dependent concatemeric viral DNA replication.

    Science.gov (United States)

    Lo Piano, Ambra; Martínez-Jiménez, María I; Zecchi, Lisa; Ayora, Silvia

    2011-09-01

    The initiation of viral double stranded (ds) DNA replication involves proteins that recruit and load the replisome at the replication origin (ori). Any block in replication fork progression or a programmed barrier may act as a factor for ori-independent remodelling and assembly of a new replisome at the stalled fork. Then replication initiation becomes dependent on recombination proteins, a process called recombination-dependent replication (RDR). RDR, which is recognized as being important for replication restart and stability in all living organisms, plays an essential role in the replication cycle of many dsDNA viruses. The SPP1 virus, which infects Bacillus subtilis cells, serves as a paradigm to understand the links between replication and recombination in circular dsDNA viruses. SPP1-encoded initiator and replisome assembly proteins control the onset of viral replication and direct the recruitment of host-encoded replisomal components at viral oriL. SPP1 uses replication fork reactivation to switch from ori-dependent θ-type (circle-to-circle) replication to σ-type RDR. Replication fork arrest leads to a double strand break that is processed by viral-encoded factors to generate a D-loop into which a new replisome is assembled, leading to σ-type viral replication. SPP1 RDR proteins are compared with similar proteins encoded by other viruses and their possible in vivo roles are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Process analytical technology (PAT) approach to the formulation of thermosensitive protein-loaded pellets: Multi-point monitoring of temperature in a high-shear pelletization.

    Science.gov (United States)

    Kristó, Katalin; Kovács, Orsolya; Kelemen, András; Lajkó, Ferenc; Klivényi, Gábor; Jancsik, Béla; Pintye-Hódi, Klára; Regdon, Géza

    2016-12-01

    In the literature there are some publications about the effect of impeller and chopper speeds on product parameters. However, there is no information about the effect of temperature. Therefore our main aim was the investigation of elevated temperature and temperature distribution during pelletization in a high shear granulator according to process analytical technology. During our experimental work, pellets containing pepsin were formulated with a high-shear granulator. A specially designed chamber (Opulus Ltd.) was used for pelletization. This chamber contained four PyroButton-TH® sensors built in the wall and three PyroDiff® sensors 1, 2 and 3cm from the wall. The sensors were located in three different heights. The impeller and chopper speeds were set on the basis of 3 2 factorial design. The temperature was measured continuously in 7 different points during pelletization and the results were compared with the temperature values measured by the thermal sensor of the high-shear granulator. The optimization parameters were enzyme activity, average size, breaking hardness, surface free energy and aspect ratio. One of the novelties was the application of the specially designed chamber (Opulus Ltd.) for monitoring the temperature continuously in 7 different points during high-shear granulation. The other novelty of this study was the evaluation of the effect of temperature on the properties of pellets containing protein during high-shear pelletization. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  2. Does Viral Marketing really Effective?

    OpenAIRE

    Chien, Ho-shen

    2012-01-01

    Abstract In this article, we examine the effectiveness of viral marketing toward young adults since the majority of Internet users are in this age group. It is also noted that we will only focus on video type of viral messages, which is the most common way to utilized viral marketing for firms. We will discuss how viral video influence consumer behavior in terms of brand images, brand choice, user experience and working memory in this paper. Our results illustrated viral video helps major...

  3. Concepts in viral pathogenesis II

    Energy Technology Data Exchange (ETDEWEB)

    Notkins, A.L.; Oldstone, M.B.A.

    1986-01-01

    This paper contains papers divided among 10 sections. The section titles are: Viral Structure and Function; Viral Constructs; Oncogenes, Transfection, and Differentiation; Viral Tropism and Entry into Cells; Immune Recognition of Viruses; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Plant and Animal Models; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Diseases in Humans; New Trends in Diagnosis and Epidemiology; and Vaccines and Antiviral Therapy.

  4. Viral mechanisms of immune evasion.

    Science.gov (United States)

    Alcami, A; Koszinowski, U H

    2000-09-01

    During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus-host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.

  5. Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome

    DEFF Research Database (Denmark)

    Katzenstein, T L; Pedersen, C; Nielsen, C

    1996-01-01

    OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty...... seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral...... load within the first year (less or more than 1.5 x 10(4) copies/ml). RESULTS: High viral load at seroconversion was followed by a significant decline within the first months (P

  6. Concentrated loads on concrete

    DEFF Research Database (Denmark)

    Lorenzen, Karen Grøndahl; Nielsen, Mogens Peter

    1997-01-01

    This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas are devel......This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas...

  7. Toward Standardization of BK Virus Monitoring: Evaluation of the BK Virus R-gene Kit for Quantification of BK Viral Load in Urine, Whole-Blood, and Plasma Specimens

    OpenAIRE

    Sueur, Charlotte; Solis, Morgane; Meddeb, Mariam; Soulier, Eric; Domingo-Calap, Pilar; Lepiller, Quentin; Freitag, Rachel; Bahram, Seiamak; Caillard, Sophie; Barth, Heidi; Stoll-Keller, Françoise; Fafi-Kremer, Samira

    2014-01-01

    Screening of BK virus (BKV) replication is recommended to identify patients at increased risk of BKV-associated diseases. However, the heterogeneity of molecular techniques hinders the establishment of universal guidelines for BKV monitoring. Here we aimed to compare the performance of the CE-marked BK virus R-gene kit (R-gene) to the performance of our in-house assay for quantification of BKV DNA loads (BKVL). A 12-specimen panel from the Quality Control for Molecular Diagnostics (QCMD) orga...

  8. PowerPoint Presentation

    Indian Academy of Sciences (India)

    Table of contents. PowerPoint Presentation · Slide 2 · Distribution of viral encephalitis · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20 · Slide 21 · Slide 22 · Slide 23 · Status dystonicus in Japanese encephalitis.

  9. Relationship Dynamics and Partner Beliefs About Viral Suppression: A Longitudinal Study of Male Couples Living with HIV/AIDS (The Duo Project).

    Science.gov (United States)

    Conroy, Amy A; Gamarel, Kristi E; Neilands, Torsten B; Dilworth, Samantha E; Darbes, Lynae A; Johnson, Mallory O

    2016-07-01

    Accurate beliefs about partners' viral suppression are important for HIV prevention and care. We fit multilevel mixed effects logistic regression models to examine associations between partners' viral suppression beliefs and objective HIV RNA viral load tests, and whether relationship dynamics were associated with accurate viral suppression beliefs over time. Male couples (N = 266 couples) with at least one HIV-positive partner on antiretroviral therapy completed five assessments over 2 years. Half of the 407 HIV-positive partners were virally suppressed. Of the 40 % who had inaccurate viral load beliefs, 80 % assumed their partner was suppressed. The odds of having accurate viral load beliefs decreased over time (OR = 0.83; p = 0.042). Within-couple differences in dyadic adjustment (OR = 0.66; p Couple-based approaches are warranted to improve knowledge of partners' viral load.

  10. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  11. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

    2004-01-01

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  12. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  13. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  14. Hepatitis viral C

    Directory of Open Access Journals (Sweden)

    Pedro A. Poma

    2011-12-01

    Full Text Available El virus de la hepatitis C se trasmite por contacto directo con la sangre de la persona infectada. La mayoría de los pacientes no presenta síntomas en la fase aguda o crónica de la hepatitis. Dos a tres décadas después, algunos pacientes progresan a la cirrosis compensada, que también es asintomática. En un examen de sangre, los anticuerpos se presentan como una sorpresa, porque no se les relaciona con un episodio de contagio. Un embarazo ocasiona la posibilidad de efectos negativos de la infección en la madre o el niño. El tratamiento actual no ofrece la certeza de cura, dependiendo del genotipo viral, y presenta efectos adversos que pueden ser severos. La cirrosis descompensada causa la mayoría de muertes relacionadas con esta infección; algunos de estos pacientes desarrollan carcinoma hepatocelular. La reproducción viral causa partículas virales diferentes del virus original, característica que ha impedido el desarrollo de una vacuna. Actualmente, la prevención consiste en evitar el contacto con sangre infectada. Este artículo revisa la infección con el virus de la hepatitis C, incluyendo los últimos progresos en tratamiento. Es necesario educar a la comunidad acerca de los efectos de este virus en la salud pública.

  15. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  16. POINT COORDINATION FUNCTION WLAN TRAFFIC LOADINGS

    African Journals Online (AJOL)

    UNN

    Authors are equally grateful to the University of Nigeria, Nsukka for providing the enabling environment and the Federal Government of. Nigeria for endowing the University with. Centre of Excellence in Networking that made this work possible. REFERENCE. 1. Anindo Mukherjee, Tarun Joshi, Dharma. P. Agrawal,.

  17. Avances recientes en HIV/SIDA: Patogénesis, historia natural y carga viral

    Directory of Open Access Journals (Sweden)

    Rafael E Campo

    1996-10-01

    Full Text Available Results of recent investigations have given us a new understanding of the pathogenesis of HIV infection. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication is the principal force driving the destruction of CD4 lymphocytes. This knowledge will lead us to design better treatment strategies directed to curtail viral replication and prevent the emergence of viral resistance, and the use of combination antiretroviral therapy is a first example of these new strategies. The concept of viral load is introduced, and we discuss the usefulness of viral load in the clinical prognosis of this disease, and its use as an aid in the decision-making process when starling or mordifyng antiretroviral therapy in our patients. (Rev Med Hered 1996; 7: 182-188.

  18. Viral interference with antigen presentation: trapping TAP.

    Science.gov (United States)

    Ressing, Maaike E; Luteijn, Rutger D; Horst, Daniëlle; Wiertz, Emmanuel J

    2013-09-01

    Following primary infection, herpesviruses persist for life in their hosts, even when vigorous anti-viral immunity has been induced. Failure of the host immune system to eliminate infected cells is facilitated by highly effective immune evasion strategies acquired by these herpesviruses during millions of years of co-evolution with their hosts. Here, we review the mechanisms of action of viral gene products that lead to cytotoxic T cell evasion through interference with the function of the transporter associated with antigen processing, TAP. The viral TAP inhibitors impede transport of peptides from the cytosol into the ER lumen, thereby preventing peptide loading onto MHC class I complexes. Recent insights have revealed a pattern of functional convergent evolution. In every herpesvirus subfamily, inhibitors of TAP function have been identified that are, surprisingly, unrelated in genome location, structure, and mechanism of action. Recently, cowpox virus has also been found to encode a TAP inhibitor. Expanding our knowledge on how viruses perturb antigen presentation, in particular by targeting TAP, not only provides information on viral pathogenesis, but also reveals novel aspects of the cellular processes corrupted by these viruses, notably the translocation of peptides by the ATP-binding cassette (ABC) transporter TAP. As the various TAP inhibitors are anticipated to impede discrete conformational transitions it is expected that crystal structures of TAP-inhibitor complexes will reveal valuable structural information on the actual mechanism of peptide translocation by TAP. Viral TAP inhibitors are also used for various (clinical) applications, for example, as effective tools in antigen presentation studies and as immunomodulators in immunotherapy for cancer, heterologous vaccination, and transplant protection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Hepatitis B viral DNA decline at loss of HBeAg is mainly explained by reduced cccDNA load--down-regulated transcription of PgRNA has limited impact.

    Science.gov (United States)

    Malmström, Sebastian; Larsson, Simon B; Hannoun, Charles; Lindh, Magnus

    2012-01-01

    Quantification of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) serum levels have become increasingly important for the assessment of clinical stage and response to treatment for chronic hepatitis B. Effective immune clearance results in reduction of viremia by 4-5 log units and HBsAg levels by 2 log, but these processes are not well understood. Thus, it is uncertain to what extent mechanisms that inhibit transcription of the pregenomic RNA (pgRNA), an RNA intermediate, contribute to suppression of viremia. Likewise, it is unclear if transcriptional regulation is important for the excessive production of surface antigen (HBsAg) that is a hallmark of HBV infection. HBV RNA and cccDNA were quantified in 19 liver biopsies from patients with chronic HBV infection, as well as in transfected Huh7.5 cells and in PLC/PRF/5 cells carrying integrated HBV genome. Patients negative for HBeAg had 2.15 log lower levels of cccDNA in liver tissue, 4.84 log lower serum levels of HBV DNA and 1.45 log lower serum levels of HBsAg, than HBeAg-positive patients. The pgRNA in liver tissue correlated strongly with cccDNA (R(2) = 0.87, ploss of HBeAg was mainly explained by reduced cccDNA load in the liver, whereas the contribution of down-regulation of pgRNA transcription was relatively small. Enhanced transcription of S-RNA does not explain excessive production of HBsAg.

  20. Predictors of CD4 health and viral suppression outcomes for formerly homeless people living with HIV/AIDS in scattered site supportive housing.

    Science.gov (United States)

    Bowen, Elizabeth A; Canfield, James; Moore, Suzanne; Hines, Midge; Hartke, Brent; Rademacher, Chrissy

    2017-11-01

    Stable housing is key to improving health outcomes for people living with HIV/AIDS. Though many formerly homeless HIV positive individuals reside in supportive housing, little research has examined biometric HIV health outcomes for residents of these programs. Through a community-based research partnership, this study analyzed secondary data from a Shelter Plus Care supportive housing program in Cincinnati, Ohio to examine the likelihood of participants achieving a healthy CD4 count (>500 cells/mm 3 ) and viral suppression (viral load housing and to identify participant characteristics associated with these outcomes. The study sample was 86 participants who entered the program between 2008 and 2016, including 50 current residents and 36 exited participants. Participants' average length of stay in Shelter Plus Care was 35.2 months (range 3.2-108.1 months) during the study period. Bivariate analysis indicated statistically significant improvements on both outcome variables, with 45% of participants achieving a healthy CD4 count and 79% achieving viral suppression by program exit or most recent time point. Participants who had health insurance at intake and who had never been incarcerated were more likely to achieve viral suppression, and longer length of stay in the program was also positively associated with viral suppression. These results add to the literature on the relationship between housing conditions and HIV health outcomes by demonstrating that residence in supportive housing is associated with improvements in CD4 count and viral load for a sample of formerly homeless persons living with HIV/AIDS, two-thirds of whom had co-occurring physical health, mental health, or substance abuse problems. Further research collaborations should expand on these findings to examine the service packages that are associated with optimal HIV health outcomes for supportive housing residents.

  1. [Molecular diagnosis of viral materno-fetal infections].

    Science.gov (United States)

    Grangeot-Keros, L

    2003-07-01

    The main viral infections prenatally detected in fetuses are: cytomegalovirus (CMV), parvovirus B19, rubella virus and varicella-zoster virus infections. Prenatal diagnosis is based on the direct detection of the virus by culture (CMV), of its antigens (CMV) or of its genome, essentially by PCR. This direct detection can be done either on fetal blood or on amniotic fluid. Prenatal diagnosis can also be performed by detection of specific IgM in fetal blood (rubella). Non specific markers of viral infections can also help diagnosis. At the present time, prenatal diagnosis is essentially based on the detection of the viral genome in amniotic fluid. In order to better appreciate the severity of fetal infections, some groups have tried to identify prognostic markers of these infections. The viral load could play a role in certain infections (CMV).

  2. Viral infections among couples for assisted reproduction in a fertility ...

    African Journals Online (AJOL)

    2012-09-28

    Sep 28, 2012 ... these clients. The males' seminal parameters were analyzed according to World Health Organization (WHO) criteria. ... Two couples had concordant HIV and HBV infections, respectively. ... for the baby) and antiretroviral therapy for HIV-positive partners to reduce the viral load before fertility treatment is.

  3. Viral infections among couples for assisted reproduction in a fertility ...

    African Journals Online (AJOL)

    Apart from separate laboratory and storage facilities, basic principles to minimize transmission are recommended: HBV vaccination in sero‑discordant partners of HBV carriers (and immunoprophylaxis for the baby) and antiretroviral therapy for HIV‑positive partners to reduce the viral load before fertility treatment is ...

  4. Environmental modulation of mucosal immunity : Opportunities in respiratory viral infections

    NARCIS (Netherlands)

    Schijf, M.A.

    2013-01-01

    The exact cause of severe disease in children during primary RSV infections is not completely clear. There is a link with viral load, but differences virus strains do not seem to be the major reason why in some children the disease manifests as a mild cold while others suffer from a severe lower

  5. [Acute hemorrhagic viral conjunctivitis].

    Science.gov (United States)

    Haicl, P; Vanista, J; Danes, L

    1992-10-01

    Two cases of acute hemorrhagic conjunctivitis are described, in which the enterovirus Coxsackie 24 was found by serological examination to be the etiological agent. The virus was important from Nigeria. The patients suffered by the acute hemorrhagic keratoconjuntivitis with transient iritic irritation without the systemic symptoms. Since now this disease with serological verification was not diagnosed in our country. The question of the viral hemorrhagic conjunctivitis and their treatment is discussed. The necessity of virological investigation in inflammations of the anterior segment is stressed.

  6. Complement and Viral Pathogenesis

    Science.gov (United States)

    Stoermer, Kristina A.; Morrison, Thomas E.

    2011-01-01

    The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. PMID:21292294

  7. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  8. Early viral replication and induced or constitutive immunity in rainbow trout families with differential resistance to Infectious hematopoietic necrosis virus (IHNV)

    Science.gov (United States)

    Purcell, M.K.; LaPatra, S.E.; Woodson, J.C.; Kurath, G.; Winton, J.R.

    2010-01-01

    The main objective of this study was to assess correlates of innate resistance in rainbow trout full-sibling families that differ in susceptibility to Infectious hematopoietic necrosis virus (IHNV). As part of a commercial breeding program, full-sibling families were challenged with IHNV by waterborne exposure at the 1 g size to determine susceptibility to IHNV. Progeny from select families (N = 7 families) that varied in susceptibility (ranging from 32 to 90% cumulative percent mortality (CPM)) were challenged again at the 10 g size by intra-peritoneal injection and overall mortality, early viral replication and immune responses were evaluated. Mortality challenges included 20–40 fish per family while viral replication and immune response studies included 6 fish per family at each time point (24, 48 and 72 h post-infection (hpi)). CPM at the 1 g size was significantly correlated with CPM at the 10 g size, indicating that inherent resistance was a stable trait irrespective of size. In the larger fish, viral load was measured by quantitative reverse-transcriptase PCR in the anterior kidney and was a significant predictor of family disease outcome at 48 hpi. Type I interferon (IFN) transcript levels were significantly correlated with an individual's viral load at 48 and 72 hpi, while type II IFN gene expression was significantly correlated with an individual's viral load at 24 and 48 hpi. Mean family type I but not type II IFN gene expression was weakly associated with susceptibility at 72 hpi. There was no association between mean family susceptibility and the constitutive expression of a range of innate immune genes (e.g. type I and II IFN pathway genes, cytokine and viral recognition receptor genes). The majority of survivors from the challenge had detectable serum neutralizing antibody titers but no trend was observed among families. This result suggests that even the most resistant families experienced sufficient levels of viral replication to trigger specific

  9. Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients.

    Science.gov (United States)

    Maskew, Mhairi; Brennan, Alana T; Westreich, Daniel; McNamara, Lynne; MacPhail, A Patrick; Fox, Matthew P

    2013-02-01

    Treatment outcomes for antiretroviral therapy (ART) patients may vary by gender, but estimates from current evidence may be confounded by disease stage and adherence. We investigated the gender differences in treatment response among HIV-positive patients virally suppressed within 6 months of treatment initiation. We analyzed data from 7,354 patients initiating ART between April 2004 and April 2010 at Themba Lethu Clinic, a large urban public sector treatment facility in South Africa. We estimated the relations among gender, mortality, and mean CD4 response in HIV-infected adults virally suppressed within 6 months of treatment initiation and used inverse probability of treatment weights to correct estimates for loss to follow-up. Male patients had a 20% greater risk of death at both 24 months and 36 months of follow-up compared to females. Older patients and those with a low hemoglobin level or low body mass index (BMI) were at increased risk of mortality throughout follow-up. Men gained fewer CD4 cells after treatment initiation than did women. The mean differences in CD4 count gains made by women and men between baseline and 12, 24, and 36 months were 28.2 cells/mm(3) (95% confidence interval [CI] 22.2-34.3), 60.8 cells/mm(3) (95% CI 71.1-50.5 cells/mm(3)), and 83.0 cells/mm(3) (95% CI 97.1-68.8 cells/mm(3)), respectively. Additionally, patients with a current detectable viral load (>400 copies/mL) and older patients had a lower mean CD4 increase at the same time points. In this initially virally suppressed population, women showed consistently better immune response to treatment than did men. Promoting earlier uptake of HIV treatment among men may improve their immunologic outcomes.

  10. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel José

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of...

  11. Plant viral vectors for delivery by Agrobacterium.

    Science.gov (United States)

    Gleba, Yuri Y; Tusé, Daniel; Giritch, Anatoli

    2014-01-01

    Plant viral vectors delivered by Agrobacterium are the basis of several manufacturing processes that are currently in use for producing a wide range of proteins for multiple applications, including vaccine antigens, antibodies, protein nanoparticles such as virus-like particles (VLPs), and other protein and protein-RNA scaffolds. Viral vectors delivered by agrobacterial T-DNA transfer (magnife