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Armenia D.,University of Rome Tor Vergata | Vandenbroucke I.,Virco | Fabeni L.,University of Rome Tor Vergata | Van Marck H.,Virco | And 15 more authors.
Journal of Infectious Diseases | Year: 2012

Background.The dynamics of raltegravir-resistant variants and their impact on virologic response in 23 HIV-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated.Methods.Integrase population sequencing and Ultra-Deep-454 Pyrosequencing (UDPS) were performed on plasma samples at baseline and at raltegravir failure. All integrase mutations detected at a frequency ≥1% were considered to be reliable for the UDPS analyses. Phylogenetic and phenotypic resistance analyses were also performed.Results.At baseline, primary resistance mutations were not detected by both population and UDPS genotypic assays; few secondary mutations (T97A-V151I-G163R) were rarely detected and did not show any statistically association either with virologic response at 24-weeks or with the development of resistant variants at failure. At UDPS, not all resistant variants appearing early during treatment evolved as major populations during failure; only specific resistance pathways (Y143R-Q148H/R-N155H) associated with an increased rate of fitness and phenotypic resistance were selected.Conclusions.Resistance to raltegravir in integrase strand transfer inhibitor-naive patients remains today a rare event, which might be changed by future extensive use of such drugs. In our study, pathways of resistance at failure were not predicted by baseline mutations, suggesting that evolution plus stochastic selection plays a major role in the appearance of integrase-resistance mutations, whereas fitness and resistance are dominant factors acting for the late selection of resistant quasispecies. © 2011 The Author.


De Luca A.,Catholic University | Di Giambenedetto S.,Catholic University | Maserati R.,Clinica Delle Malattie Infettive Policlinico San Matteo | Gianotti N.,Hospital San Raffaele | And 9 more authors.
Antiviral Therapy | Year: 2011

Background: There is not yet consensus on interpretation of genotypic HIV-1 resistance to darunavir (DRV). We validated existing rules and a newly derived score. Methods: Protease inhibitor (PI)-failing patients starting a DRV/ritonavir-based regimen, with available baseline resistance genotypes, were extracted from three Italian databases. Virological response (VR) was analysed between 4 and 32 follow-up weeks, defined as a drop from baseline HIV RNA of ≥2 log10 or a value <50 copies/ml if the last measurement had been obtained at ≤12 weeks and as HIVRNA<50 copies/ml if it had been obtained at >12 weeks of follow-up. DRV/ritonavir resistance was interpreted by seven algorithms. A new weighted score (DRV-2009) was derived and validated, analysing associations of protease mutations with VR. Results: A total of 217 patients were analysed, with a mean (±sd) follow-up time of 17 (±9) weeks. At baseline, median HIV RNA was 4.26 log10 copies/ml (IQR 3.11-5.03); VR was achieved in 135/217 (62%) patients. Adjusting for use of a new drug class, number of previous PIs experienced, CD4+ T-cell count and HIV RNA, only the Rega DRV/ritonavir interpretation was significantly associated with VR (per increase in susceptibility category, OR 1.94, 95% CI 1.32-2.86; P<0.001). The DRV-2009 score V11I+L33F+R41K+I47V+2 *I-50V+2 I54M+K55R+D60E+L74P+L76V+N88D+2*L89V-L10I/ V-I13V-G16E-G48V-F53I/L-I62V-I66F-V77I (<0 indicating susceptibility, 0-1 intermediate resistance and ≥2 resistance) correlated with VR in the derivation set (n=132, R=0.395; P<0.001). In the validation set (n=85), after adjusting for mutual interpretation and new use of enfuvirtide, DRV-2009 (P=0.017) and Rega (P=0.013) were both independently associated with VR. Conclusions: In contrast to the other algorithms, both the DRV-2009 score and Rega interpretation showed a robust predictive capacity of VR to DRV/ritonavir-containing regimens. ©2011 International Medical Press.


Picano E.,CNR Institute of Clinical Physiology | Piccaluga E.,Hospital Sacco | Padovani R.,University of Udine | Traino C.A.,University of Pisa | And 2 more authors.
Journal of Atrial Fibrillation | Year: 2014

The benefits of cardiac imaging are immense, and modern cardiac electrophysiology (EP) requires the extensive and versatile use of a variety of cardiac imaging and radiology-based techniques. In the cardiac electrophysiology lab, doses can range around a reference effective dose (ED) of 15 milliSievert corresponding to 750 chest x-rays for a cardiac radiofrequency ablation, ranging from less than 2 to > 60 mSv. The reference dose for a regular pacemaker or ICD implant is 4 mSv (range 1.4-17) and for a CRT implant is 22 mSv (range 2.2-95). Doses on the order of magnitude of 10-100 milliSievert (mSv) correspond to a low (albeit definite, not negligible) additional lifetime risk of fatal and non-fatal cancer from between 1 in 1000 (10 mSv) to 1 in 100 (100 mSv). The increasing use and complexity of cardiac electrophysiology techniques have not been matched by increasing awareness and knowledge by prescribers and practitioners. The protection of doctors is just as important as protection of patients. Most experienced (and most exposed) interventional cardiologists and electrophysiologists have an exposure per annum of around 5 mSv, two to three times higher than diagnostic radiologists, with a typical cumulative lifetime attributable risk on the order of magnitude of 1 cancer (fatal and non-fatal) per 100 exposed subjects. Operator dose per procedure correlates somewhat with the patient dose, but may be typically 1000 times lower depending upon the shielding employed (one unit of incidence scatter dose for the operator when 1000 units of incident dose are given to the patient). However, adequate radiation protection training and diligent protection can reduce this radiation exposure by 90%. The priority given to radioprotection in every cardiology department is an effective strategy for primary prevention of cancer, a strong indicator of the quality of the cardiology division, and the most effective shielding for enhancing the safety of patients, doctors, and staff.


PubMed | Interventional Cardiology Unit, University of Pisa, University of Udine, Hospital Sacco and CNR Institute of Clinical Physiology
Type: Review | Journal: Journal of atrial fibrillation | Year: 2016

The benefits of cardiac imaging are immense, and modern cardiac electrophysiology (EP) requires the extensive and versatile use of a variety of cardiac imaging and radiology-based techniques. In the cardiac electrophysiology lab, doses can range around a reference effective dose (ED) of 15 milliSievert corresponding to 750 chest x-rays for a cardiac radiofrequency ablation, ranging from less than 2 to > 60 mSv. The reference dose for a regular pacemaker or ICD implant is 4 mSv (range 1.4-17) and for a CRT implant is 22 mSv (range 2.2-95). Doses on the order of magnitude of 10-100 milliSievert (mSv) correspond to a low (albeit definite, not negligible) additional lifetime risk of fatal and non-fatal cancer from between 1 in 1000 (10 mSv) to 1 in 100 (100 mSv). The increasing use and complexity of cardiac electrophysiology techniques have not been matched by increasing awareness and knowledge by prescribers and practitioners. The protection of doctors is just as important as protection of patients. Most experienced (and most exposed) interventional cardiologists and electrophysiologists have an exposure per annum of around 5 mSv, two to three times higher than diagnostic radiologists, with a typical cumulative lifetime attributable risk on the order of magnitude of 1 cancer (fatal and non-fatal) per 100 exposed subjects. Operator dose per procedure correlates somewhat with the patient dose, but may be typically 1000 times lower depending upon the shielding employed (one unit of incidence scatter dose for the operator when 1000 units of incident dose are given to the patient). However, adequate radiation protection training and diligent protection can reduce this radiation exposure by 90%. The priority given to radioprotection in every cardiology department is an effective strategy for primary prevention of cancer, a strong indicator of the quality of the cardiology division, and the most effective shielding for enhancing the safety of patients, doctors, and staff.

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