Suchergebnisse

IntroductionHIV‐2 infection is endemic in West Africa and some European countries, namely Portugal. HIV‐2 antiretroviral (ARV) treatment presents some restrains related to intrinsic resistance to non‐nucleoside reverse transcriptase inhibitors (NNRTI) and fusion inhibitors, and poorer response to protease inhibitors (PI).Material and MethodsRetrospective observational study of a cohort of 135 infected HIV‐2 patients, diagnosed between 1989 and 2008.ObjectivesEvaluation of epidemiologic, clinical, immunologic and virologic progression, comparing to groups of patients (naïve vs ARV experienced); characterization of therapeutic, immunologic and virologic response. SPSS version 20.0 was used for statistical analysis.ResultsThe study included 135 patients: 41% (n=55) naïve and 59% (n=80) with ARV experience. The comparison between groups (naïve vs ARV) revealed: male prevalence 76% vs 50%; mean age 54.5 years vs 54.8 (p=0.90); main geographic origin Guiné Bissau (47% vs 44%) and Portugal (22% vs 33%); and transmission mainly acquired by heterosexual contact (87% vs 80%). Mean time since diagnosis was 14 vs 13 years (p=0.31); 2% vs 50% presented AIDS criteria at diagnosis (p<0.001) and 93% vs 38% registered TCD4>350 cell/mm3 at diagnosis (p<0.001). Immunological evolution showed no significant decline in naïve population (Δ=−67 cell/mm3 – p=0.18) and a significant recovery in ARV experienced (Δ=+207 cell/mm3 – p<0.001). Global mortality rate found was 18% (6% vs 13% – p=0.122). Eighty patients initiated ARV: 84% presented a time interval of ARV exposure between 0–5 years (42%) and 5–10 years (42%). Fifty percent experienced ≤2 ARV regimens and the remaining >2 regimes. Considering the first ARV therapy: 56% initiated PI, 30% NTRI and 5% integrase inhibitor (II)‐based regimens. Currently, 54 patients maintain regular follow‐up and ARV therapy: 60% NTRI+PI; 37% NRTI+PI+II and 3% NRTI+II. TDF/FTC is the backbone in 56%. Most frequent PIs are LPV/r (54%), DRV/r (19%) and ATV/r (12%). Mean time of exposure to NRTI=3 years, PI=7 years and II=2 years. Immunologic recovery was sustained for each of the ARV class considered (NRTI Δ=+144 cell/mm3; PI=Δ+92 cell/mm3; II=Δ=+116 cell/mm3).ConclusionsThis is a cohort accompanied for a long period and the majority of patients present extensive ARV experience. The ARV‐experienced patients registered a favourable response to treatment, with sustained immune recovery (Δ=+207 cell/mm3) and virologic control in 74%. Immunologic behaviour evidenced a sustained gain for each of the ARV class considered.

Despite the increasing optimization of combined antiretroviral therapy (cART) regimens in the last decades, a significant percentage of patients still do not achieve viral replication control. We present a retrospective analysis focusing on human immunodeficiency virus (HIV)‐infected population on cART, followed at our ambulatory care clinic between 1st January and 31st December 2011, in order to identify the causes of virological failure. From the 1895 patients in our population we included 1854 in the study. Ten percent (187) of the included patients had detectable HIV RNA (≥40 cp/mL) at the time of last laboratory evaluation: 70,1% were males, mean age was 46 years and 72,7% were Portuguese. Patients with detectable HIV RNA were divided into group A (HIV RNA <200 cp/mL) ‐ 78 (41,7%) patients and group B (HIV RNA ≥200 cp/mL) 109 (58,3%) patients. The comparison of both groups revealed an higher mean count of TCD4+ (568 vs 334 cells/mm3; p<0,001) in group A, although similar mean TCD4+ count at time of cART initiation (276 vs 262 cells/mm3; p=0,412). Group A patients experienced longer exposure to cART (10 vs 8 years; p<0,05) and have undergone, on average, 3 previous regimens (p<0,05). With regard to cARV current regimen: 32,1% patients in group A and 30,3% in group B were prescribed non‐nucleoside reverse transcriptase inhibitors based regimes and 51,3% patients in Group A and 59,6% in group B were under cARV based on Protease inhibitors. The identified causes of virologic failure for patients with detectable HIV RNA were: poor adherence (54%); unsuccessful retention in care (14,4%); sporadic detectable HIV RNA (40≤viral load<200), "blips" (14,4%); mutations of resistance to ARVs (13,4%); intolerance to the current regimen (2,1%) and pharmacokinetics drug interactions (1,6%). The estimated rate of virological failure was 10,1% in this population. Insufficient adherence and unsuccessful retention in care were identified in 68,4% of treatment failed patients as main causes of virological failure. Failure of therapy due to intolerance or adverse effects was reported in 2,1% of cases, reflecting a better safety profile and tolerability of recent prescribed regimens. Early identification of causes of virologic failure, timely adjustment of therapeutic regimens, and the adoption of measures to promote adherence and retention in care are key factors for successful treatment of HIV‐infected patients.

IntroductionLate HIV diagnosis is common and associated with an increased risk of clinical progression, blunted immune response on antiretroviral (ARV) therapy and higher risk of drug toxicity. Across Europe, more than a third of patients are diagnosed late and consequently delay medical care. European Consensus definition group identify as late presentation (LP) persons, presenting for care, with a CD4 count below 350 cell/mm3 or presenting with AIDS‐defining event, regardless of CD4 cell count. Additionally, advanced HIV disease (AD) is defined by a CD4 count below 200 cell/mm3 or an AIDS defining condition in persons presenting to care.Materials and MethodsRetrospective observational study of a cohort of 705 HIV‐infected patients diagnosed between 1986 and 2014 and medically followed at an Infectious Diseases Service in Lisbon.ObjectivesEvaluate LP rate evolution in the last three decades (10‐year time intervals considered: 1986–1995; 1996–2005; 2006–2014); compare clinic, immunologic, virologic and therapeutic response over time. Identify main reasons responsible for late HIV diagnosis in order to promote optimized intervention strategies. SPSS version 20.0 was used for statistical analysis.ResultsStudy included 705 patients HIV diagnosed during 3 time intervals: group A n=82 [1986–1995]; group B n=332 [1996–2005]; group C n=291 [2006–2014]. Demographic and epidemiological characterization revealed (A vs B vs C): male predominance of 79% vs 66% vs 66%; mean age at diagnosis 30 vs 36 vs 42 years; Portugal (82% vs 70% vs 58%) and Africa (13% vs 23% vs 29%) as the main places of birth; transmission by heterosexual contact in 21% vs 47% vs 62%, MSM in 21% vs 15% vs 23% and IVDU in 57% vs 35% vs 13%. Mean CD4 at diagnosis was 362 vs 344 vs 377 cell/mm3. Considering the time intervals, LP was found in 52% vs 56% vs 52% of patients and AD in 31% vs 38% vs 35%, respectively. At first health care encounter, 46% vs 43% vs 39% of individuals presented with AIDS. Over follow up, the vast majority initiated ARV (95% vs 98% vs 84%) and mean CD4 at that time was 254 vs 282 vs 250 cell/mm3. The last immunologic and virologic determination available registered mean CD4 of 657 vs 644 vs 584 cell/mm3 and undetectable HIV plasma RNA in 92% vs 84% vs 82% of treated patients.ConclusionsThis study evidenced a maintained LP rate, slightly above 50% in each of the three analyzed last decades, and one‐third of patients presented AD at HIV diagnosis. At initial health care contact, nearly 40% of individuals met AIDS clinical or immunological criteria.

Planck Collaboration. ; The characterization of the Galactic foregrounds has been shown to be the main obstacle in thechallenging quest to detect primordial B-modes in the polarized microwave sky. We make use of the Planck-HFI 2015 data release at high frequencies to place new constraints on the properties of the polarized thermal dust emission at high Galactic latitudes. Here, we specifically study the spatial variability of the dust polarized spectral energy distribution (SED), and its potential impact on the determination of the tensor-to-scalar ratio, r. We use the correlation ratio of the angular power spectra between the 217 and 353 GHz channels as a tracer of these potential variations, computed on different high Galactic latitude regions, ranging from 80% to 20% of the sky. The new insight from Planck data is a departure of the correlation ratio from unity that cannot be attributed to a spurious decorrelation due to the cosmic microwave background, instrumental noise, or instrumental systematics. The effect is marginally detected on each region, but the statistical combination of all the regions gives more than 99% confidence for this variation in polarized dust properties. In addition, we show that the decorrelation increases when there is a decrease in the mean column density of the region of the sky being considered, and we propose a simple power-law empirical model for this dependence, which matches what is seen in the Planck data. We explore the effect that this measured decorrelation has on simulations of the BICEP2-Keck Array/Planck analysis and show that the 2015 constraints from these data still allow a decorrelation between the dust at 150 and 353 GHz that is compatible with our measured value. Finally, using simplified models, we show that either spatial variation of the dust SED or of the dust polarization angle are able to produce decorrelations between 217 and 353 GHz data similar to the values we observe in the data. ; The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, J.A., and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement No. 267934. ; Peer Reviewed

ESA ; CNES (France) ; CNRS/INSU-IN2P3-INP (France) ; ASI (Italy) ; CNR (Italy) ; INAF (Italy) ; NASA (USA) ; DoE (USA) ; STFC (UK) ; UKSA (UK) ; CSIC (Spain) ; MINECO (Spain) ; JA (Spain) ; RES (Spain) ; Tekes (Finland) ; AoF (Finland) ; CSC (Finland) ; DLR (Germany) ; MPG (Germany) ; CSA (Canada) ; DTU Space (Denmark) ; SER/SSO (Switzerland) ; RCN (Norway) ; SFI (Ireland) ; FCT/MCTES (Portugal) ; ERC (EU) ; PRACE (EU) ; UK BIS NEI grants ; Office of Science of the U.S. Department of Energy ; Canada Foundation for Innovation under Compute Canada ; Government of Ontario ; University of Toronto ; Science and Technology Facilities Council ; Office of Science of the U.S. Department of Energy: DE-AC02-05CH11231 ; Science and Technology Facilities Council: ST/L000768/1 ; Science and Technology Facilities Council: ST/L000652/1 ; Science and Technology Facilities Council: ST/J005673/1 ; Science and Technology Facilities Council: ST/M00418X/1 ; Science and Technology Facilities Council: ST/L000393/1 ; Science and Technology Facilities Council: ST/M007065/1 ; Science and Technology Facilities Council: ST/K00333X/1 ; The Planck full mission cosmic microwave background (CMB) temperature and E-mode polarization maps are analysed to obtain constraints on primordial non-Gaussianity (NG). Using three classes of optimal bispectrum estimators - separable template-fitting (KSW), binned, and modal we obtain consistent values for the primordial local, equilateral, and orthogonal bispectrum amplitudes, quoting as our final result from temperature alone f(NL)(local) = 2.5 +/- 5.7, f(NL)(equil) = 16 +/- 70, and f(NL)(ortho) = 34 +/- 33 (68% CL, statistical). Combining temperature and polarization data we obtain f(NL)(local) = 0.8 +/- 5.0, f(NL)(equil) = 4 +/- 43, and f(NL)(ortho) = 26 +/- 21 (68% CL, statistical). The results are based on comprehensive cross-validation of these estimators on Gaussian and non-Gaussian simulations, are stable across component separation techniques, pass an extensive suite of tests, and are consistent with estimators based on measuring the Minkowski functionals of the CMB. The effect of time-domain de-glitching systematics on the bispectrum is negligible. In spite of these test outcomes we conservatively label the results including polarization data as preliminary, owing to a known mismatch of the noise model in simulations and the data. Beyond estimates of individual shape amplitudes, we present model-independent, three-dimensional reconstructions of the Planck CMB bispectrum and derive constraints on early universe scenarios that generate primordial NG, including general single-field models of inflation, axion inflation, initial state modifications, models producing parity-violating tensor bispectra, and directionally dependent vector models. We present a wide survey of scale-dependent feature and resonance models, accounting for the look elsewhere effect in estimating the statistical significance of features. We also look for isocurvature NG, and find no signal, but we obtain constraints that improve significantly with the inclusion of polarization. The primordial trispectrum amplitude in the local model is constrained to be g(NL)(local) = (9.0 +/- 7.7) x 10(4) (68% CL statistical), and we perform an analysis of trispectrum shapes beyond the local case. The global picture that emerges is one of consistency with the premises of the Lambda CDM cosmology, namely that the structure we observe today was sourced by adiabatic, passive, Gaussian, and primordial seed perturbations.