Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Multiwavelength observations of 3C 454.3 II. The AGILE 2007 December campaign

We report on the second AGILE multiwavelength campaign of the blazar 3C 454.3 during the first half of December 2007. This campaign involved AGILE, Spitzer, Swift,Suzaku,the WEBT consortium,the REM and MITSuME telescopes,offering a broad band coverage that allowed for a simultaneous sampling of the synchrotron and inverse Compton (IC) emissions.The 2-week AGILE monitoring was accompanied by radio to optical monitoring by WEBT and REM and by sparse observations in mid-Infrared and soft/hard X-ray energy bands performed by means of Target of Opportunity observations by Spitzer, Swift and Suzaku, respectively.The source was detected with an average flux of~250x10^{-8}ph cm^-2s^-1 above 100 MeV,typical of its flaring states.The simultaneous optical and gamma-ray monitoring allowed us to study the time-lag associated with the variability in the two energy bands, resulting in a possible ~1-day delay of the gamma-ray emission with respect to the optical one. From the simultaneous optical and gamma-ray fast flare detected on December 12, we can constrain the delay between the gamma-ray and optical emissions within 12 hours. Moreover, we obtain three Spectral Energy Distributions (SEDs) with simultaneous data for 2007 December 5, 13, 15, characterized by the widest multifrequency coverage. We found that a model with an external Compton on seed photons by a standard disk and reprocessed by the Broad Line Regions does not describe in a satisfactory way the SEDs of 2007 December 5, 13 and 15. An additional contribution, possibly from the hot corona with T=10^6 K surrounding the jet, is required to account simultaneously for the softness of the synchrotron and the hardness of the inverse Compton emissions during those epochs.Comment: 13 pages, 8 figures, 2 tables, Accepted for publication in Ap

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 < 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 > 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 < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 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

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Investigating the peculiar emission from the new VHE gamma-ray source H1722+119

The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes observed the BL Lac object H1722+119 (redshift unknown) for six consecutive nights between 2013 May 17 and 22, for a total of 12.5 h. The observations were triggered by high activity in the optical band measured by the KVA (Kungliga Vetenskapsakademien) telescope. The source was for the first time detected in the very high energy (VHE, $E > 100$ GeV) $\gamma$-ray band with a statistical significance of 5.9 $\sigma$. The integral flux above 150 GeV is estimated to be $(2.0\pm 0.5)$ per cent of the Crab Nebula flux. We used contemporaneous high energy (HE, 100 MeV $< E < 100$ GeV) $\gamma$-ray observations from Fermi-LAT (Large Area Telescope) to estimate the redshift of the source. Within the framework of the current extragalactic background light models, we estimate the redshift to be $z = 0.34 \pm 0.15$. Additionally, we used contemporaneous X-ray to radio data collected by the instruments on board the Swift satellite, the KVA, and the OVRO (Owens Valley Radio Observatory) telescope to study multifrequency characteristics of the source. We found no significant temporal variability of the flux in the HE and VHE bands. The flux in the optical and radio wavebands, on the other hand, did vary with different patterns. The spectral energy distribution (SED) of H1722+119 shows surprising behaviour in the $\sim 3\times10^{14} - 10^{18}$ Hz frequency range. It can be modelled using an inhomogeneous helical jet synchrotron self-Compton model.Comment: 12 pages, 5 figures, 2 table

Multiwavelength Evidence for Quasi-periodic Modulation in the Gamma-ray Blazar PG 1553+113

We report for the first time a gamma-ray and multi-wavelength nearly-periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope (LAT) we have discovered an apparent quasi-periodicity in the gamma-ray flux (E >100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/-0.08 year-period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the OVRO, Tuorla, KAIT, and CSS monitoring programs and Swift UVOT. The optical cycle appearing in ~10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multi-wavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.Comment: 8 pages, 5 figures. Accepted to The Astrophysical Journal Letters. Corresponding authors: S. Ciprini (ASDC/INFN), S. Cutini (ASDC/INFN), S. Larsson (Stockholm Univ/KTH), A. Stamerra (INAF/SNS), D. J. Thompson (NASA GSFC

Long-term multi-wavelength variability and correlation study of Markarian 421 from 2007 to 2009

We study the multi-band variability and correlations of the TeV blazar Mrk 421 on year time scales, which can bring additional insight on the processes responsible for its broadband emission. We observed Mrk 421 in the very high energy (VHE) gamma-ray range with the Cherenkov telescope MAGIC-I from March 2007 to June 2009 for a total of 96 hours of effective time after quality cuts. The VHE flux variability is quantified with several methods, including the Bayesian Block algorithm, which is applied to data from Cherenkov telescopes for the first time. The 2.3 year long MAGIC light curve is complemented with data from the Swift/BAT and RXTE/ASM satellites and the KVA, GASP-WEBT, OVRO, and Mets\"ahovi telescopes from February 2007 to July 2009, allowing for an excellent characterisation of the multi-band variability and correlations over year time scales. Mrk 421 was found in different gamma-ray emission states during the 2.3 year long observation period. Flares and different levels of variability in the gamma-ray light curve could be identified with the Bayesian Block algorithm. The same behaviour of a quiet and active emission was found in the X-ray light curves measured by Swift/BAT and the RXTE/ASM, with a direct correlation in time. The behaviour of the optical light curve of GASP-WEBT and the radio light curves by OVRO and Mets\"ahovi are different as they show no coincident features with the higher energetic light curves and a less variable emission. The fractional variability is overall increasing with energy. The comparable variability in the X-ray and VHE bands and their direct correlation during both high- and low-activity periods spanning many months show that the electron populations radiating the X-ray and gamma-ray photons are either the same, as expected in the Synchrotron-Self-Compton mechanism, or at least strongly correlated, as expected in electromagnetic cascades.Comment: Corresponding authors: Ann-Kristin Overkemping ([email protected]), Marina Manganaro ([email protected]), Diego Tescaro ([email protected]), To be published in Astronomy&Astrophysics (A&A), 12 pages, 9 figure