Systemic inflammation and residual viraemia in HIV-positive adults on protease inhibitor monotherapy: a cross-sectional study.

Increased levels of markers of systemic inflammation have been associated with serious non-AIDS events even in patients on fully suppressive antiretroviral therapy. We explored residual viremia and systemic inflammation markers in patients effectively treated with ritonavir-boosted protease inhibitor monotherapy (PImono)

Fast Neutron And Gamma-ray Detectors For The Csiro Air Cargo Scanner

oS(FNDA2006)074 © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence

The seasonal detection of strawberry viruses in Victoria, Australia

AbstractPCR tests were adopted from international, peer-reviewed literature and developed for the detection of Strawberry mottle sadwavirus (SMoV), Strawberry crinkle cytorhabdovirus (SCV), Strawberry mild yellow edge potexvirus (SMYEV), Strawberry vein banding caulimovirus (SVBV), Beet pseudos yellows crinivirus (BPYV), and Strawberry pallidosis associated crinivirus (SPaV) in Victoria, Australia. The PCR tests were applied to 23 positive control plants infected with one or more viruses and these plants have been tested monthly from May 2005 to April 2007. Our results have indicated that the viruses were most reliably detected by PCR during May-October. In November, December and January of each year a decline in the number of positive PCR results for BPYV, SVBV and SPaV was observed. Twelve positive control plants maintained at the AQIS post entry quarantine screenhouse at Knoxfield, Victoria, and also infected with one or more viruses, were tested monthly from August 2006 to April 2007. A similar decline in the ability to detect SMoV, SVBV and SPaV in the AQIS positive control plants was observed in 2006/07 and November was the least reliable month for detection of strawberry viruses in these plants. These results indicate that spring and autumn may be the optimal times for PCR detection of strawberry viruses in south east Australia.Keywords: Strawberry mottle sadwavirus; Strawberry crinkle cytorhabdovirus; Strawberry mild yellow edge potexvirus; Strawberry vein banding caulimovirus; Beet pseudos yellows crinivirus; Strawberry pallidosis associated crinivirus; detection; polymerase chain reaction; PCR; certificatio

No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV

OBJECTIVE: Excessive weight gain has been reported with integrase strand transfer inhibitors (INSTIs). We evaluated weight changes in virologically-suppressed adults with HIV who switched from non-INSTI regimens to raltegravir- or dolutegravir-containing antiretroviral therapy. DESIGN: Retrospective single-centre cohort. METHODS: Adults who switched to raltegravir or dolutegravir before or between January-2015 and October-2017 were identified. Virologically-suppressed, treatment-experienced (≥2 years) individuals, ≥6 months on INSTI, with weight measurements ≤2years pre- and post-switch were included. Our analysis used a random effects model with linear slope pre- and post-INSTI with adjustment for age, gender, ethnicity, pre-switch-regimen (protease inhibitor vs. non-protease inhibitor), and raltegravir vs. dolutegravir use. RESULTS: 378 individuals, 81.2% male, 70.1% white ethnicity, median age of 49 years, median of four weight measurements per participant, and median weight and body mass index (BMI) at switch, of 76.6 kg, and 25.3 kg/m respectively were included. Weight increased by an average of 0.63 kg/year (95% CI 0.17-1.09) pre-switch with no overall change in rate of weight gain post-switch [+0.05 kg/year (-0.61-0.71, p = 0.88)]. In our adjusted model, a transition from minimal weight change to weight gain post-switch was isolated to older individuals though this lacked statistical significance [e.g. +1.59 kg/year (-0.26-3.45) if aged 65 years]. Our findings did not differ by gender, ethnicity, pre-switch regimen, or raltegravir vs. dolutegravir. Similar results were seen for BMI and after adjusting for fixed nucleoside/nucleotide reverse transcriptase inhibitor backbone. CONCLUSION: We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically-suppressed individuals

Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53–63) and 58 (53–63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders

Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).

OBJECTIVES: Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir. METHODS: Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3 or 4 clinical or laboratory adverse events (AEs) related to the PEP medication. RESULTS: Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P  =   0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3 or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P  < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P  < 0.001). There were no HIV seroconversions in the study period. CONCLUSIONS: The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP

Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2. Funding: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth

Consensus on the assessment of systemic sclerosis–associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment

INTRODUCTION: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. METHODS: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. RESULTS: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. CONCLUSION: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice

Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

Objectives: We performed a network meta‐analysis of PEP randomized clinical trials to evaluate the best regimen. / Methods: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three‐drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir‐boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat‐boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non‐completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow‐up and adverse events. / Results: Participants were mostly men who have sex with men (n = 832, 75%) with non‐occupational exposure to HIV (89.86%). Four‐hundred fifty‐four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non‐completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58–1.56; EVG/c: OR 0.65 95% CI 0.30–1.37; RAL: OR 0.68 95% CI 0.41–1.13; and MVC: OR 0.69 95% CI 0.47–1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non‐completion at day 28, switching, lost to follow‐up or adverse events and MVC for PEP discontinuations due to adverse events. / Conclusions: Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single‐Tablet Regimen

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5–300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46–1.00) for the first round and 0.55 (0.44–1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47–1.00)). Criterion validity showed a 78 (73–84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research