The ANTARES deep-sea neutrino telescope comprises a three-dimensional array of photomultipliers to detect the Cherenkov light induced by upgoing relativistic charged particles originating from ...neutrino interactions in the vicinity of the detector. The large scattering length of light in the deep sea facilitates an angular resolution of a few tenths of a degree for neutrino energies exceeding 10
TeV. In order to achieve this optimal performance, the time calibration procedures should ensure a relative time calibration between the photomultipliers at the level of ∼1
ns. The methods developed to attain this level of precision are described.
Abstract
Objectives
Even in an ‘optimal’ health system, patients’ characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV ...care continuum in France, a country with a universal free healthcare system.
Methods
We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat’AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987.
Results
Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% of person-time on ART and 74.6% and 62.9% suppressed, respectively. Young men born abroad were found to spend the smallest person-time with non-detectable viral load (53% for MSW and 58.1% for MSM).
Conclusions
Despite free access to care and universal ART in France, disparities remain in the HIV continuum care across age, country of birth and way of HIV acquisition. Clinical and public health interventions targeting specific patients’ conditions are needed.
There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined ...antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.
We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, had CD4 cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4 cell count and HIV-RNA via inverse probability weighting.
Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 13,65 months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.
With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.
Atmospheric neutrinos are produced during cascades initiated by the interaction of primary cosmic rays with air nuclei. In this paper, a measurement of the atmospheric
νμ + ¯νμ energy spectrum in the ...energy range 0.1–200 TeV is presented, using data collected by the ANTARES underwater neutrino telescope from 2008 to 2011. Overall,
the measured flux is ∼25 % higher than predicted by the conventional neutrino flux, and compatible with the measurements
reported in ice. The flux is compatible with a single power-law dependence with spectral index γmeas = 3.58 ± 0.12. With the present statistics the contribution of prompt neutrinos cannot be established.
Unlike their younger counterparts, some of today's older HIV patients were diagnosed before the advent of highly active antiretroviral therapy (HAART). The psychosocial and behavioral outcomes of ...people living with HIV (PLWH) have been widely studied, and associated factors are well known. However, their evolution both in terms of age and diagnosis-specific cohort effects is not well understood.
Data from the ANRS-VESPA2 cross-sectional survey, representative of French PLWH, were used to investigate whether psychosocial and behavioral outcomes such as quality of life, need for support and HIV status disclosure, evolve under both the influence of patients' age and diagnosis-specific cohort effects. A semi-parametric generalized additive model (GAM) was employed. The physical and mental components of health-related quality of life, the need for material and moral support, and HIV-status disclosure, constituted our outcomes.
Non-linear diagnosis-specific cohort effects were found for physical and mental QoL and HIV-status disclosure. Overall, physical QoL was better in recently diagnosed patients than in those diagnosed in the early 1980s. An increasing influence of diagnosis-specific cohort effects between 1983 and 1995 was observed. No cohort effects were noticeable between 1996 and 2000, while an increasing influence was apparent for patients diagnosed with HIV from 2000 to 2011 (year of study). For mental QoL, the only increase was observed in participants diagnosed with HIV between 1983 and 2000. The relationship between diagnosis-specific cohort effects and HIV status disclosure was negative overall: participants diagnosed after 2000 were much less likely to disclose than those diagnosed before 1995. The effect of age was significantly associated with all outcomes, with a non-linear influence on mental QoL and with the need for material/moral support.
Psychosocial and behavioral outcomes are complex processes which can be explained in different ways by a combination of the clinical and social contexts which PLWH are exposed to at the time of diagnosis, and by developmental characteristics. A greater understanding of these processes could inform healthcare policy-making for specific HIV generations and different HIV age groups.
Context. The source(s) of the neutrino excess reported by the IceCube Collaboration is unknown. The TANAMI Collaboration recently reported on the multiwavelength emission of six bright, variable ...blazars which are positionally coincident with two of the most energetic IceCube events. Objects like these are prime candidates to be the source of the highest-energy cosmic rays, and thus of associated neutrino emission. Aims. We present an analysis of neutrino emission from the six blazars using observations with the ANTARES neutrino telescope. Methods. The standard methods of the ANTARES candidate list search are applied to six years of data to search for an excess of muons – and hence their neutrino progenitors – from the directions of the six blazars described by the TANAMI Collaboration, and which are possibly associated with two IceCube events. Monte Carlo simulations of the detector response to both signal and background particle fluxes are used to estimate the sensitivity of this analysis for different possible source neutrino spectra. A maximum-likelihood approach, using the reconstructed energies and arrival directions of through-going muons, is used to identify events with properties consistent with a blazar origin. Results. Both blazars predicted to be the most neutrino-bright in the TANAMI sample (1653−329 and 1714−336) have a signal flux fitted by the likelihood analysis corresponding to approximately one event. This observation is consistent with the blazar-origin hypothesis of the IceCube event IC 14 for a broad range of blazar spectra, although an atmospheric origin cannot be excluded. No ANTARES events are observed from any of the other four blazars, including the three associated with IceCube event IC20. This excludes at a 90% confidence level the possibility that this event was produced by these blazars unless the neutrino spectrum is flatter than −2.4.
Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of ...treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.
Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.
LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).
Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.
Objectives
The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)‐coinfected individuals and to characterize the continuum ...in Europe on 1 January 2015, prior to widespread access to direct‐acting antiviral (DAA) therapy.
Methods
Stages included in the continuum were as follows: anti‐HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow‐up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow‐up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment.
Results
Numbers and percentages for the stages of the HCV continuum of care were as follows: anti‐HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow‐up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001).
Conclusions
In the proposed HCV continuum of care for HIV/HCV‐coinfected individuals, we found major gaps at all stages, with almost 20% of anti‐HCV‐positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre‐DAA era.
Objectives
HIV‐positive people have increased risk of infection‐related malignancies (IRMs) and infection‐unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on ...future IRM and IURM incidence.
Methods
People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence.
Results
A total of 15 648 people contributed 95 033 person‐years of follow‐up, of whom 610 developed 643 malignancies IRMs: 388 (60%); IURMs: 255 (40%). After adjustment, a higher IRM incidence was associated with a lower CD4 count adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL, independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5‐year period from 3.1 (95% CI 1.5–5.9) per 1000 person‐years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person‐years over the same period.
Conclusions
Demographic and HIV‐related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV‐infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV‐infected populations.
Objectives
People living with HIV (PLHIV) are at a higher risk of dying by suicide than the general population. Epidemiological data regarding determinants of suicide in PLHIV are scarce. The aim of ...this study was thus to study demographic, socio‐economic, psychiatric history and immunovirological characteristics associated with death from suicide in the French multicenter Dat'AIDS cohort, from January 2000 to July 2013.
Methods
This was a nested case–control study. All deceased PLHIV during the study period who died by suicide and whose medical files could be checked were included as cases. Controls were selected using incidence density sampling. For each case, up to four controls were selected among all actively followed PLHIV at the index date (date of death of cases). Controls were matched for time from HIV diagnosis (5‐year periods) and clinical centre.
Results
Seventy cases and 279 controls were included in the study. By multivariable analysis, the factors significantly associated with death from suicide were: not having children, active or substituted drug consumption, alcohol intake > 20 g/day or history of alcohol abuse, history of depressive disorder and/or of attempted suicide, and psychotropic drug intake. Conversely, age, gender, country of birth, positive HCV serology and HIV‐related factors, such as AIDS status, use of combination antiretroviral therapy (cART), nadir and current CD4 counts and HIV viral load, were not significantly associated with the risk of death from suicide.
Conclusions
In the cART era, HIV‐related factors are not associated with a higher risk of suicide mortality. Suicide prevention measures should target PLHIV with the psychological morbidities observed in our cohort.
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