Local epidemics gone viral: Evolution and diffusion of the Italian HIV-1 recombinant form CRF60_BC

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy

No impact of previous NRTIs resistance in HIV positive patients switched to DTG+2NRTIs under virological control: Time of viral suppression makes the difference

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA <50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA >50 copies/mL or one HIV-RNA >1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12-78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted 0.98, 95%CI 0.96-0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF

A large area CsI RICH Detector in ALICE at LHC

A 1m2 CsI RICH prototype has been successfully tested in a hadron beam at CERN SPS. The prototype, fully equipped with 15k electronic channels, has been used to identify particles coming from pi-Be interactions. Track reconstruction has been performed by using a telescope consisting of four gas pad chambers. A detailed description of the detector will be presented and results from the test will be discussed.List of figuresFigure 1 Expected proton and antiproton yields including jet quenching mechanism in central Pb-Pb collisions at LHC.Figure 2 Schematic view of the HMPID CsI-RICHFigure 3 Experimental layout used at the SPS/H4 test beamFigure 4 Distributions of the mean number, per ring, of pad hits (Npad), electrons (Ntot) and Cherenkov photoelectrons (Nres) as a function of the single-electron mean pulse heightFigure 5 Mean single-electron pulse height as a function of high voltage measured at the centre of each of the four photocathodesFigure 6 Evaluation of the uniformity of the chamber gain for the photocathode PC32Figure 7 Azimuthal distribution of the photon pad hits in the Cherenkov fiducial zone (HV=2050 V)Figure 8 Photon angle (a) and track Cherenkov angle (b) distributions for beam events at the SPSFigure 9 Track density on the HMPID cathode plane in real 350 GeV/c pi--Be eventsFigure 10 Three dimensional display of an SPS 350 GeV/c pi--Be event. Eleven tracks are reconstructed in the telescope by requiring one hit on each pad chamber to reconstruct a track</UL

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

The Present Development of CsI Rich Detectors for the ALICE Experiment at CERN

The ALICE Collaboration plans to implement a 12m^2 array consisting of 7 proximity focussed C6F^14 liquid radiator RICH modules devoted to the particle identification in the momentum range: 1 GeV/c - 3.5 GeV/c for pions and kaons. A large area CSI-RICH prototype has been designed and built with the aim to validate the detector parameter assumptions made to predict the performance of the High Momentum Particle Identification System (HMPID) of the ALICE Experiment. The main elements of the prototype will be described with emphasis on the engineering solutions adopted. First results from the analysis of multitrack events recorded with this prototype exposed to hadron beams at the CERN SPS will be discussedList of FiguresFigure 1 General view of the ALICE lay-outFigure 2 Schematic layout of the fast CsI-RICHFigure 3 Perspective view of the HMPID layout with the seven RICH modules tilted according to their position with respect to the interaction vertex. The frame that supports the detectors is also shownFigure 4 Top view of the photodetector anode plane with the wire support spacer. One CsI board, out of six forming the pad cathode plane, is also shown.Figure 5 Perspective view of the HMPID honeycomb panel with the three radiator vesselsFigure 6 Cut away view of the HMPID CsI-RICH showing separately each detector component. Kapton buses that carry signals from the pads to the readout electronics are also shownFigure 7 a)number of resolved photoelectrons per event, b)reconstructed Cherenkov angle per photonFigure 8 C6F14 transmission plots before and after the molecular sieve purificationFigure 9 Display plot showing an SPS event. Three tracks are reconstructed by using the tracking chamber telescope, the associated rings are shown in the HMPID prototypeThis publication also appears as INT-98-20

High-Dose, Extended-Interval Colistin Administration in Critically Ill Patients: Is This the Right Dosing Strategy? A Preliminary Study

In critically ill patients with otherwise untreatable nosocomial infection due to gram-negative bacteria susceptible only to colistin, a high-dose, extended-interval colistin dosing regimen is, according to the pharmacokinetic/pharmacodynamic behavior of the drug, associated with low renal toxicity and high efficacy

A progress report on the development of the CsI-RICH detector for the ALICE experiment at LHC

The particle identification in ALICE (A Large Ion Collider Experiment) at LHC will be achieved by two complementary systems based on time of flight measurement, at low $p_t$, and on the Ring Imaging Cherenkov (RICH) technique, at $p_t$ ranging from 2 to 5 GeV/$c$, respectively. The High Momentum PID (HMPID) system will cover $\sim$5\% of the phase space, the single arm detector array beeing composed by seven 1.3$\times$1.3 m$^2$ CsI-RICH modules placed at 4.7 m from the interaction point where a density of about 50 particles/m$^2$ is expected.\\ A 1 m$^2$ prototype, 2/3 of HMPID module size, has been successfully tested at the CERN/PS beam where 18 photoelectrons per event have been obtained with 3 GeV/c pions and 10 mm liquid $\mathrm{C}_6\mathrm{F}_{14}$ radiator. Mechanical problems related to the liquid radiator vessel construction have been solved and the prototype, fully equipped, will be tested at the CERN/SPS to investigate the PID capability in high particle density events.\\ In this report, after an introductory discussion on the requirements for PID in ALICE, the HMPID prototype is described and the main results of beam tests on large area CsI photocathodes, operated in RICH detectors, are given