Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.S

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes.MethodsThis national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up).FindingsOf 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index 2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes.InterpretationMDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens.FundingWellcome Trust, Joint Global Health Trials

Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte-like cells

Cyclosporin A (CsA) is an immunosuppresor drug that has been used in the treatment of several types of inflammatory diseases. In some of them the inhibition of T-lymphocyte activation does not suitably account for the observed beneficial effect, suggesting that CsA could act on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by U937 monocyte cells. Undifferentiated and dimethylsulfoxide (DMSO) differentiated U937 cells were incubated with different concentrations of CsA (200, 20 and 2 ng/mL) in the presence or absence of phorbol-myristateacetate (PMA). Interleukin-1g (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. At the highest concentration used (200 ng/mL) CsA decreased the basal and stimulated secretion of all the inflammatory cytokines studied in both undifferentiated and differentiated cells, with the only exception of PMA-stim ulated IL-1 secretion by undifferentiated cells. However, only basal secretion of interleukin-8 in both undifferentiated and DMSO-differentiated U937 cells was significantly reduced by CsA at the highest concentration (200 ng/ mL). At therapeutic concentrations in vivo, CsA exerts a predominant effect on IL-8 secretion by human mononuclear phagocytes

KM3NeT front-end and readout electronics system: hardware, firmware, and software

he KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host water-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large volume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced by neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for calibration of the photomultiplier signal and positioning of the optical module, and all associated electronics boards. By design, the total electrical power consumption of an optical module has been capped at seven Watts. We present an overview of the front-end and readout electronics system inside the optical module, which has been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life time of at least 20 years

Architecture and performance of the KM3NeT front-end firmware

The KM3NeT infrastructure consists of two deep-sea neutrino telescopes being deployed in the Mediterranean Sea. The telescopes will detect extraterrestrial and atmospheric neutrinos by means of the incident photons induced by the passage of relativistic charged particles through the seawater as a consequence of a neutrino interaction. The telescopes are configured in a three-dimensional grid of digital optical modules, each hosting 31 photomultipliers. The photomultiplier signals produced by the incident Cherenkov photons are converted into digital information consisting of the integrated pulse duration and the time at which it surpasses a chosen threshold. The digitization is done by means of time to digital converters (TDCs) embedded in the field programmable gate array of the central logic board. Subsequently, a state machine formats the acquired data for its transmission to shore. We present the architecture and performance of the front-end firmware consisting of the TDCs and the state machine

KM3NeT front-end and readout electronics system: hardware, firmware, and software

The KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host water-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large volume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced by neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for calibration of the photomultiplier signal and positioning of the optical module, and all associated electronics boards. By design, the total electrical power consumption of an optical module has been capped at seven Watts. We present an overview of the front-end and readout electronics system inside the optical module, which has been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life time of at least 20 year