1,721,076 research outputs found
HIV TREATMENT SIMPLIFICATION: OUTCOMES OF SWITCHING HIV-1 PATIENTS TO PROTEASE-INHIBITOR MAINTENANCE MONOTHERAPY
Get PDFThe work in this thesis characterised the virological outcomes of HIV-1 patients on second-line ART switching to boosted-darunavir maintenance monotherapy in sub-Saharan Africa and explored their determinants, with the aim of providing evidence to inform practice and policy.
Firstly, I took advantage of samples and data collected within a trial of maintenance monotherapy that was conducted in Yaoundé, Cameroon, between August 2014 and July 2015. The trial population was composed of HIV-1 positive adults who were receiving suppressive second-line ART with two NRTIs and a ritonavir-boosted protease inhibitor (PI/b). Patients were randomised to either a switch to maintenance monotherapy with ritonavir-boosted darunavir (DRV/r) for 48 weeks or to continue their current triple ART regimen.
My first question was to investigate the virological outcomes and the relationship between viraemia and drug resistance. I used stored samples to investigate the presence of drug-resistance associated mutations (RAMs) in peripheral blood mononuclear cells (PBMC) collected at study entry (while patients were virologically suppressed on triple ART) and in follow-up plasma samples collected at the time of virological rebound on DRV/r monotherapy. I analysed the viral genomes by Sanger sequencing and ultra-deep sequencing (UDS) and used phylogenetics to assess their relatedness. The resistance analyses focused on reverse transcriptase and protease; in a subset of patients I also sequenced the gag gene to identify mutations in cleavage sites and other regions. I then used the resistance data alongside the available demographic, clinical and laboratory data to identify predictors of virological outcomes by statistical modelling. The results were interesting. I found that presence of RAMs at study entry affecting the NRTIs and the NNRTIs were predictive of a reduced (rather than increased) risk of virological rebound during follow-up on DRV/r monotherapy and the effect was independent of adherence levels. I also found that despite a high prevalence of viraemia during DRV/r monotherapy, there was no emergence of new protease resistance even by sensitive UDS, thus confirming data from previous studies conducted in Europe. While this observation was reassuring as it indicated no loss of treatment options in the monotherapy arm, I wondered whether there were other adverse consequences of frequent viraemia during DRV/r monotherapy.
I thus investigated the kinetics of soluble CD27 (sCD27), a marker of immune activation and inflammation that a previous study from our group had linked to residual viraemia in subjects on suppressive ART. I tested prospective samples taken before and four weeks after the switch from triple ART to DRV/r monotherapy and observed that median sCD27 levels increased significantly after simplification, with the effect driven by a subset of the patients. I used various control populations to place the findings into context using different control populations. Hence, I propose that sCD27 may serve as an indicator of a risk of viraemia, a hypothesis that needs to be investigated prospectively.
One additional research question was related to Hepatitis B Virus (HBV). My research hypothesis was that in a HBV hyperendemic setting like Cameroon, discontinuation of HBV active agents in people with HIV-1 could abolish a prophylactic effect against HBV acquisition and reactivation. To address this question, I measured markers of HBV infection prospectively in MANET trial participants. The results showed discontinuation of NRTIs was associated with a risk of both de-novo acquisition and reactivation of HBV. This represents another factor that makes DRV/r monotherapy undesirable for Cameroon and sub-Saharan Africa in general
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Developing and applying serological and molecular skills to the virological analysis of HIV-infected patients from Kumasi, Ghana
No full textBackground : Virological monitoring is critical in the management of HIV-infected patients, providing a standard in the assessment of disease prognosis and progression, guiding the initiation of ART and treatment selection, monitoring therapeutic success and establishing treatment failure and drug resistance. The absence of viral load monitoring can impact upon individual and public health through failure to maintain viral suppression, and increased risk of drug resistance. HIV management at the KATH HIV clinic, Kumasi, Ghana, does not include virological monitoring due to the lack of laboratory infrastructure and technical skills, thus the virological response to ART among treated patients at the centre is not fully understood. Moreover, data on the prevalence of HCV infection in both the general population and HIV-positive patients in Ghana are limited, with seroprevalence estimates ranging from 0.5% to 18.7% documented among different Ghanaian populations, possibly due to differences in study populations and the serological assays employed. Furthermore, these previous studies did not attempt confirmation of HCV status by PCR or RIBA. The aim of this study is to determine the HIV virological response in a HIV/HBV co-infected cohort from KATH, ascertain the specificity and sensitivity of commercially available HCV serological assays, and develop an assay that could be used as an alternative for HCV RNA testing in Kumasi.
Methods: 247 HIV/HBV co-infected patients attending the KATH HIV clinic were recruited into a prospective HIV and viral hepatitis study, of which HIV-1 viral load was determined for 183 ART-experienced patients at study entry using the Abbott Real Time HIV-1 assay. The HIV-1 viral load detection among patients who had been on ART for at least 24 weeks was assessed. HIV positive samples from KATH with known HCV-RNA status were tested with two automated anti-HCV antibody assays, the Abbott Architect anti-HCV, Vitros Anti-HCV, and two manual EIAs, Monolisa HCV Ag-Ab ULTRA, and the ORTHO HCV 3.0 ELISA System with Enhanced SAVe. Of the last three assays the performance and the respective assay cut-offs likely to be indicative of RNA positivity were evaluated using their PCR and Architect results as reference. The development of an in-house indirect sandwich HCV core antigen EIA which could be used as an alternative for HCV-RNA testing was attempted.
Results: Overall, 58/183 (37.4%) patients who received treatment for at least 24 weeks showed a viral load >40 copies/mL with a median level of 826 copies/mL (IQR: 65 - 26752). Their CD4 T-cell counts were lower compared to patients with undetectable viral load (P= 0.002, Mann Whitney U test). Among the four HCV antibody assays the Ortho was found to be the most specific assay that could be employed in a limited resource setting such as Kumasi, and an S/CO ratio of 3.65 was found to be most likely to be indicative of HCV RNA positivity. The HCV core EIA development was not completed in time due to poor activity of commercially available agents.
Conclusion: Through this study, skills in HIV viral load and EIA development have been acquired that could be applied to improve virological monitoring at KATH with the necessary infrastructure in place. Further studies are required to identify factors that are associated with poor viral response in this cohort. The ORTHO HCV 3.0 ELISA System with Enhanced SAVe can be regarded as a suitable diagnostic tool for HCV infection in Kumasi, but further studies are required to establish the S/CO ratio most likely to be indicative of HCV RNA positivity
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Hepatitis B and C in Malawi: Epidemiology, Disease Burden and Opportunities for a Public Health Treatment Programme
Get PDFAbstract
In sub-Saharan Africa, hepatitis B virus (HBV) infection is the principal cause of liver cirrhosis and hepatocellular carcinoma (HCC). Mortality from cirrhosis and HCC is projected to rise beyond 2030 unless adult HBV treatment programmes are implemented. Infant HBV vaccination was introduced across sub-Saharan Africa between 1994-2014, and in Malawi in 2002 where it is given at 6, 10 and 14 weeks of life. Hepatitis C virus (HCV) is an important contributor to liver disease globally, with an estimated population prevalence of 1% in sub-Saharan Africa. In Southern Africa there is a paucity of HCV prevalence data, with no previous random probability-sampling community studies.
A hospital-based study of cirrhosis and HCC in a tertiary hospital, and seroprevalence studies in an urban township, were conducted in Blantyre, Malawi, to determine HBV and HCV prevalence and HBV vaccine impact. Of 97,386 censused individuals, single stage non-replacement age-stratified probability sampling was used to select 6,073 individuals who were tested for hepatitis B surface antigen (HBsAg) in a community serosurvey. HBsAg-positive individuals aged ≥16 were recruited to assess treatment eligibility. Among individuals aged ≥16 in the serosurvey, 1661 (51%) were randomly selected for HCV antigen/antibody (Ag/Ab) testing with confirmatory HCV RNA PCR. Prevalence estimates were standardised to census age and sex distribution using post-stratification proportional fitting.
In the hospital study, the population attributable fraction (PAF) of HBV to cirrhosis and HCC was 23.1% (95% CI 15.7- 29.8) and 71.5% (59.3- 80.1) respectively among 250 consecutively recruited patients. For HCV the PAF was 1.6% (95% CI -0.4 – 3.6) for cirrhosis and 4.8% (-0.1, 9.5) for HCC. Patients with HCC were diagnosed at an advanced stage with a median tumour size of 12.6cm and a median survival of 1.3 months. Six-month survival was 67% (59.0- 73.8) among patients with cirrhosis.
Standardised HBsAg prevalence in serosurvey participants born prior to, and after HBV vaccine introduction, was 5.1% (95% CI 4.3- 6.1) and 0.3% (95% CI 0.1- 0.6) respectively. Three-dose vaccination coverage was 97.4% (1141/1171) among 1171/2085 children aged ≤10 years with known vaccine status. By comparison of participants born 5 years before and after vaccine introduction, vaccine impact was 95.9% (95% CI 70.6- 99.4). Treatment eligibility was assessed in 94/150 HBsAg positive people aged ≥16 years from the serosurvey, of whom 24/93 (26%) were HIV positive, and 16/24 (67%) were receiving antiretroviral therapy containing tenofovir, with HBV DNA suppression. Among 69 HIV-negative HBsAg positive individuals, 3,6 and 9% were eligible for HBV treatment by WHO, EASL and AASLD criteria respectively.
Standardised HCV Ag/Ab prevalence was 0.78% (95% CI 0.46- 1.33) and HCV RNA prevalence was 0.18% (95% CI 0.06- 0.53). HCV Ag/Ab positive individuals were older than the general population but no differences in sex, educational, employment or marital status were observed.
In an urban township in Malawi, HBV prevalence was intermediate at 5.1% among unvaccinated adults. Infant HBV vaccination was associated with a vaccine impact of 96%. Among HBsAg-positive adults, one quarter were HIV-positive and 3-9% of HIV-negative adults were eligible for antiviral therapy. Estimated population HCV RNA prevalence was 0.2%. Future prevalence studies should sample rural communities and specific risk groups. HCC is diagnosed at an advanced stage with a poor prognosis in Malawi, and HBV is an important cause. The burden of HBV and HCV associated liver disease represents both a challenge, and an opportunity to implement public health treatment programmes to reverse rising liver-related mortality in Southern Africa
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