507 results on '"S. Bonora"'
Search Results
202. Malignant Melanoma in People Living with HIV/AIDS: Can We Know More, Can We Do Better?
- Author
-
Trunfio M, Ribero S, Bonora S, Di Perri G, Quaglino P, and Calcagno A
- Subjects
- Clinical Trials as Topic, Humans, Immunologic Factors therapeutic use, Melanoma epidemiology, Disease Management, HIV Infections complications, Melanoma diagnosis, Melanoma therapy
- Abstract
Thanks to the advancement in understanding of molecular mechanisms driving immune surveillance, we have now approached a revolutionary era for the treatment of malignant melanoma (MM). Meanwhile, people living with HIV/AIDS (PLWHA) are aging and non-AIDS-related cancers have become a leading cause of death. Both HIV infection and melanoma share common immune-pathological pathways: immune checkpoints are being targeted for melanoma immunotherapy and investigated as a "shock and kill" strategy for latency reversion among HIV-positive individuals. Nevertheless, a substantial lack of information exists on epidemiology, clinical features, and management of MM in HIV, due to compartmentalized approaches and poor awareness about the problem. In this narrative review, we aimed at analyzing available data regarding MM in PLWHA to point out key knowledge gaps and future opportunities from an integrated dermatology, oncology, and infectious diseases standpoint. To date, a strong association between HIV infection and MM risk still needs to be effectively demonstrated; nevertheless, once this cancer has developed in HIV-positive people, it shows more aggressive course, worse prognosis, and seemingly peculiar clinical and histological features. Despite these challenges, a syndemic framework should lead us toward a tailored and multidisciplinary approach not to miss valuable opportunities from the worst situations including the enrolment of HIV-positive patients in the ongoing trials with immune checkpoint inhibitors., (Copyright: © 2019 Permanyer.)
- Published
- 2019
- Full Text
- View/download PDF
203. Optical characterization and adaptive optics correction of polymer adaptive lens aberrations.
- Author
-
Quintavalla M, Santiago F, Bonora S, and Restaino S
- Abstract
Adaptive lenses based on fluid-filled polymer membranes allow for great simplification of optical systems providing large focal length variation and reduction of size, weight, and power consumption. However, aberrations can reduce their optical quality and, for some demanding applications, their correction by means of adaptive optics implies increased complexity, especially if reflective wavefront correctors are used. In this work, we characterize two adaptive lenses in terms of optical power and aberrations. We then correct the gravity-induced aberrations by means of a multiactuator adaptive lens in a closed-loop adaptive optics configuration, with a minimal increase in optical setup complexity. The improvements in the performance of an imaging system are shown.
- Published
- 2019
- Full Text
- View/download PDF
204. The clinical pharmacology of integrase inhibitors.
- Author
-
Di Perri G, Calcagno A, Trentalange A, and Bonora S
- Subjects
- Animals, Drug Development methods, Drug Therapy, Combination, HIV Infections enzymology, HIV Infections virology, HIV Integrase Inhibitors adverse effects, HIV Integrase Inhibitors pharmacology, Humans, Life Expectancy, Practice Guidelines as Topic, HIV Infections drug therapy, HIV Integrase Inhibitors administration & dosage, Virus Replication drug effects
- Abstract
Introduction : Treatment of HIV infection has consistently evolved in the last three decades. A steady improvement in efficacy tolerability, safety, and practical aspects of treatment intake has made HIV infection much easier to manage over the long term, and in optimal treatment conditions the life expectancy of persons living with HIV infection now approaches the values of the general population. The last category of antiretrovirals to be fully developed for clinical use is the one of strand-transfer integrase inhibitors (INSTIs). Areas covered : In this review, the evolution of the knowledge on INSTIs use in the clinical setting is reviewed, analyzed, and interpreted. Emphasis is placed on the properties possibly accounting for several superiority results achieved by INSTIs in non-inferiority designed comparative clinical trials, which led to their inclusion as first line options in all versions of HIV therapeutic guidelines. Expert commentary : Some unprecedented clinical-pharmacological properties of INSTIs, such as their rapid and sustained action against HIV replication, the optimal tolerability and safety profile and a clinically proven robust genetic barrier are the main factors justifying the successful clinical use of INSTIs. Based on these unique features, novel INSTIs-based treatment modalities are being developed, including the reduction of antiretroviral regimens to two drugs only.
- Published
- 2019
- Full Text
- View/download PDF
205. Effect of ABCC2 and ABCG2 Gene Polymorphisms and CSF-to-Serum Albumin Ratio on Ceftriaxone Plasma and Cerebrospinal Fluid Concentrations.
- Author
-
Allegra S, Cardellino CS, Fatiguso G, Cusato J, De Nicolò A, Avataneo V, Bonora S, D'Avolio A, Di Perri G, and Calcagno A
- Subjects
- Adult, Aged, Anti-Bacterial Agents blood, Anti-Bacterial Agents cerebrospinal fluid, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents therapeutic use, Ceftriaxone pharmacokinetics, Ceftriaxone therapeutic use, Female, Humans, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics, Ceftriaxone blood, Ceftriaxone cerebrospinal fluid, Meningitis, Bacterial drug therapy, Multidrug Resistance-Associated Proteins genetics, Neoplasm Proteins genetics, Polymorphism, Single Nucleotide
- Abstract
We measured ceftriaxone pharmacokinetics in patients' plasma and cerebrospinal fluid (CSF) and assessed the influence of biometric, demographic, genetic (ABCB1, ABCC2, ABCB11, ABCG2, and SLCO1A2 polymorphisms) and pathological features. Adult patients with signs and symptoms of central nervous system infections, receiving intravenous ceftriaxone, were enrolled. Ceftriaxone plasma and CSF concentrations were measured by high-precision liquid chromatographic methods; allelic discrimination was performed by real-time polymerase chain reaction. Forty-three patients were included: median ceftriaxone maximal concentration was 15,713 ng/mL in plasma and 3512 ng/mL in CSF with a CSF-to-plasma ratio of 0.3. ABCC2 1249 rs2273697 (P = .027) and ABCG2 1194+928 rs13120400 (P = .015) variants were significantly associated with CSF concentrations and CSF-to-plasma ratios. At linear regression analysis, CSF-to-serum albumin ratio was an independent predictor of ceftriaxone CSF concentrations (P = .001; also in those with intact blood-brain barrier: P = .031) and CSF-to-plasma ratio (P = .001; also in those with blood-brain barrier impairment: P = .040). We here report the role of transporters' genetic variants as well as of blood-brain barrier permeability in predicting ceftriaxone exposure in the central nervous system., (© 2018, The American College of Clinical Pharmacology.)
- Published
- 2018
- Full Text
- View/download PDF
206. Peripheral and cerebrospinal fluid immune activation and inflammation in chronically HIV-infected patients before and after virally suppressive combination antiretroviral therapy (cART).
- Author
-
Merlini E, Iannuzzi F, Calcagno A, Bai F, Trunfio M, d'Arminio Monforte A, Bonora S, and Marchetti G
- Subjects
- AIDS Dementia Complex cerebrospinal fluid, AIDS Dementia Complex drug therapy, Adult, Female, Humans, Male, Middle Aged, RNA, Viral blood, RNA, Viral cerebrospinal fluid, AIDS Dementia Complex immunology, Anti-HIV Agents therapeutic use, HIV Infections cerebrospinal fluid, HIV Infections drug therapy, HIV Infections immunology
- Abstract
Cerebrospinal fluid (CSF)/plasma HIV-RNA ratio has been associated with residual neurocognitive impairment on cART, leading us to hypothesize a specific peripheral and/or CSF immune feature in patients with high CSF/plasma ratio (≥ 1). In patients with diverse pre-cART CSF/plasma ratio (61/70 with CSF/plasma ratio < 1, L-CSF, 9/70 with CSF/plasma ratio ≥ 1, H-CSF), we investigated the effects of 12 months of effective cART on peripheral and CSF inflammatory markers, on T cell activation/maturation and HIV/CMV-specific intracellular cytokine pattern. We also studied the possible clinical association between peripheral/CSF pro-inflammatory milieu and neurocognitive screening tests (MMSE, FAB, IHDS). Prior to cART, the two groups were comparable for peripheral and CSF inflammation, T cell activation/proliferation and maturation, and HIV/CMV-specific response. Upon cART initiation, both H-CSF and L-CSF featured a significant reduction in plasma TNF-α and circulating CD8 activation, with a redistribution of memory/naïve T cell subsets in L-CSF alone. In the CSF compartment, cART seemed able to reduce pro-inflammatory cytokine/chemokine levels in both H-CSF and L-CSF patients. Interestingly, despite a reduction in the pro-inflammatory milieu, no changes were shown in neurocognitive screening tests in both patients' groups. We hereby show that 12-month cART is able to reduce intratechal and peripheral pro-inflammatory burden; a longer cART exposure and a more comprehensive neuropsychological evaluation might be necessary to gain a broader insight into the possible effects on neurocognitive performance.
- Published
- 2018
- Full Text
- View/download PDF
207. Fast stabilization of a high-energy ultrafast OPA with adaptive lenses.
- Author
-
Negro M, Quintavalla M, Mocci J, Ciriolo AG, Devetta M, Muradore R, Stagira S, Vozzi C, and Bonora S
- Abstract
The use of fast closed-loop adaptive optics has improved the performance of optical systems since its first application. Here we demonstrate the amplitude and carrier-envelope phase stabilization of a high energy IR optical parametric amplifier devoted to Attosecond Science exploiting two high speed adaptive optical systems for the correction of static and dynamic instabilities. The exploitation of multi actuator adaptive lenses allowed for a minimal impact on the optical setup.
- Published
- 2018
- Full Text
- View/download PDF
208. Effect of a contact lens on mouse retinal in vivo imaging: Effective focal length changes and monochromatic aberrations.
- Author
-
Zhang P, Mocci J, Wahl DJ, Meleppat RK, Manna SK, Quintavalla M, Muradore R, Sarunic MV, Bonora S, Pugh EN Jr, and Zawadzki RJ
- Subjects
- Aberrometry, Animals, Mice, Mice, Inbred C57BL, Ophthalmoscopes, Pupil physiology, Contact Lenses, Cornea physiopathology, Corneal Wavefront Aberration physiopathology, Refraction, Ocular physiology, Retina diagnostic imaging
- Abstract
For in vivo mouse retinal imaging, especially with Adaptive Optics instruments, application of a contact lens is desirable, as it allows maintenance of cornea hydration and helps to prevent cataract formation during lengthy imaging sessions. However, since the refractive elements of the eye (cornea and lens) serve as the objective for most in vivo retinal imaging systems, the use of a contact lens, even with 0 Dpt. refractive power, can alter the system's optical properties. In this investigation we examined the effective focal length change and the aberrations that arise from use of a contact lens. First, focal length changes were simulated with a Zemax mouse eye model. Then ocular aberrations with and without a 0 Dpt. contact lens were measured with a Shack-Hartmann wavefront sensor (SHWS) in a customized AO-SLO system. Total RMS wavefront errors were measured for two groups of mice (14-month, and 2.5-month-old), decomposed into 66 Zernike aberration terms, and compared. These data revealed that vertical coma and spherical aberrations were increased with use of a contact lens in our system. Based on the ocular wavefront data we evaluated the effect of the contact lens on the imaging system performance as a function of the pupil size. Both RMS error and Strehl ratios were quantified for the two groups of mice, with and without contact lenses, and for different input beam sizes. These results provide information for determining optimum pupil size for retinal imaging without adaptive optics, and raise critical issues for design of mouse optical imaging systems that incorporate contact lenses., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
209. Evaluation of coronary features of HIV patients presenting with ACS: The CUORE, a multicenter study.
- Author
-
Peyracchia M, De Lio G, Montrucchio C, Omedè P, d'Ettore G, Calcagno A, Vullo V, Cerrato E, Pennacchi M, Sardella G, Manga P, GrossoMarra W, Vullo F, Fedele F, Biondi-Zoccai G, Moretti C, Vachiat A, Bonora S, Rinaldi M, Mancone M, and D'Ascenzo F
- Subjects
- Acute Coronary Syndrome diagnostic imaging, Acute Coronary Syndrome mortality, Acute Coronary Syndrome physiopathology, Aged, Antiretroviral Therapy, Highly Active, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease mortality, Coronary Artery Disease physiopathology, Female, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections mortality, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Plaque, Atherosclerotic, Predictive Value of Tests, Prevalence, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Ultrasonography, Interventional, Acute Coronary Syndrome epidemiology, Coronary Artery Disease epidemiology, Coronary Vessels diagnostic imaging, Coronary Vessels physiopathology, HIV Infections epidemiology
- Abstract
Background and Aims: The risk of recurrence of myocardial infarction (MI) in HIV patients presenting with acute coronary syndrome (ACS) is well known, but there is limited evidence about potential differences in coronary plaques compared to non-HIV patients., Methods: In this multicenter case-control study, HIV patients presenting with ACS, with intravascular-ultrasound (IVUS) data, enrolled between February 2015 and June 2017, and undergoing highly active antiretroviral therapy (HAART), were retrospectively compared to non-HIV patients presenting with ACS, before and after propensity score with matching, randomly selected from included centers. Primary end-point was the prevalence of multivessel disease. Secondary end-points were the prevalence of abnormal features at IVUS, the incidence of major-acute-cardiovascular-events (MACE), a composite end point of cardiovascular death, MI, target lesion revascularization (TLR), stent thrombosis (ST), non-cardiac death and target vessel revascularization (TVR). For each end-point, a subgroup analysis was conducted in HIV patients with CD4 cell count <200/mm
3 ., Results: Before propensity score, 66 HIV patients and 120 non-HIV patients were selected, resulting in 20 and 40 after propensity score. Patients with multivessel disease were 11 and 17, respectively (p = 0.56). IVUS showed a lower plaque burden (71% vs. 75%, p < 0.001) and a higher prevalence of hyperechoic non-calcified plaques (100% vs. 35%, p < 0.05) in HIV patients; a higher prevalence of hypoechoic plaques (7% vs. 0%, p < 0.05), a higher incidence of MACE (17.4% vs. 9.1% vs. l'8.0%, p < 0.05), MI recurrence (17.2% vs. 0.0% vs. 2.3%, p < 0.05), and ST (6.7% vs. 0.3% vs. 03%, p < 0.05) in HIV patients with CD4 < 200/mm3 ., Conclusions: Our study may provide a part of the pathophysiological basis of the differences in coronary arteries between HIV-positive and HIV-negative patients, suggesting that the former present with peculiar morphological features at IVUS, even after adjustment for clinical variables. Furthermore, we confirmed that an advanced HIV infection is associated with a high risk of non-calcific plaques and with a worse prognosis, including cardiovascular events and ACS recurrence., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
210. Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir.
- Author
-
Focà E, Calcagno A, Bonito A, Cusato J, Domenighini E, D'Avolio A, Quiros Roldan E, Trentini L, Castelnuovo F, Di Perri G, Castelli F, and Bonora S
- Subjects
- Adult, Atazanavir Sulfate blood, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Protease Inhibitors blood, HIV Protease Inhibitors pharmacokinetics, Humans, Polymorphism, Single Nucleotide genetics, Pregnancy, Pregnancy Complications, Infectious drug therapy, Pregnancy Trimester, Third, Prospective Studies, Ritonavir blood, Atazanavir Sulfate pharmacokinetics, Atazanavir Sulfate therapeutic use, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, Liver-Specific Organic Anion Transporter 1 genetics, Pregnane X Receptor genetics, Ritonavir pharmacokinetics, Ritonavir therapeutic use
- Abstract
Atazanavir-ritonavir concentrations change over time during pregnancy in HIV-positive patients; the impact of genetic variants is unknown. Twenty patients were enrolled in this study; plasma and intracellular concentrations of antiretrovirals were measured, in addition to single-nucleotide polymorphisms in transport-related genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1- and pregnane-X-receptor-encoding genes affected third-trimester atazanavir exposure. In this prospective study, genetic variants partially explained the observed interpatient variability in third-trimester exposure to antiretrovirals., (Copyright © 2018 American Society for Microbiology.)
- Published
- 2018
- Full Text
- View/download PDF
211. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.
- Author
-
Calcagno A, Pinnetti C, De Nicolò A, Scarvaglieri E, Gisslen M, Tempestilli M, D'Avolio A, Fedele V, Di Perri G, Antinori A, and Bonora S
- Subjects
- Adult, Anti-HIV Agents blood, Chromatography, High Pressure Liquid, Dideoxynucleosides blood, Drug Administration Schedule, Drug Monitoring methods, Female, HIV Infections blood, HIV Infections cerebrospinal fluid, HIV Infections diagnosis, Humans, Italy, Male, Middle Aged, Tandem Mass Spectrometry, Time Factors, Treatment Outcome, Anti-HIV Agents administration & dosage, Anti-HIV Agents cerebrospinal fluid, Dideoxynucleosides administration & dosage, Dideoxynucleosides cerebrospinal fluid, HIV Infections drug therapy
- Abstract
Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml
-1 , P = 0.038 and 123 vs. 49 ng ml-1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment., (© 2018 The British Pharmacological Society.)- Published
- 2018
- Full Text
- View/download PDF
212. First-line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison.
- Author
-
Taramasso L, Di Biagio A, Maggiolo F, Tavelli A, Lo Caputo S, Bonora S, Zaccarelli M, Caramello P, Costantini A, Viscoli C, d'Arminio Monforte A, and Cozzi-Lepri A
- Abstract
Objectives: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens., Methods: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan-Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed., Results: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30-43) years vs. 33 (IQR 27-39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257-421) cells/μL vs. 447 (IQR 347-580) cells/μL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92-4.74) log
10 copies/mL vs. 4.23 (IQR 3.81-4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89-5.80], for toxicity (RH 2.23; 95% CI 1.05-4.73) for intolerance (RH 5.17; 95% CI 2.66-10.07) and for proactive switch (RH 10.96; 95% CI 3.17-37.87) than those starting RPV., Conclusions: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures., (© 2018 British HIV Association.)- Published
- 2018
- Full Text
- View/download PDF
213. Wavefront correction in two-photon microscopy with a multi-actuator adaptive lens.
- Author
-
Bueno JM, Skorsetz M, Bonora S, and Artal P
- Abstract
A multi-actuator adaptive lens (AL) was incorporated into a multi-photon (MP) microscope to improve the quality of images of thick samples. Through a hill-climbing procedure the AL corrected for the specimen-induced aberrations enhancing MP images. The final images hardly differed when two different metrics were used, although the sets of Zernike coefficients were not identical. The optimized MP images acquired with the AL were also compared with those obtained with a liquid-crystal-on-silicon spatial light modulator. Results have shown that both devices lead to similar images, which corroborates the usefulness of this AL for MP imaging.
- Published
- 2018
- Full Text
- View/download PDF
214. Diagnostic accuracy of new and old cognitive screening tools for HIV-associated neurocognitive disorders.
- Author
-
Trunfio M, Vai D, Montrucchio C, Alcantarini C, Livelli A, Tettoni MC, Orofino G, Audagnotto S, Imperiale D, Bonora S, Di Perri G, and Calcagno A
- Abstract
Objectives: Considering the similarities between HIV-associated neurocognitive disorders (HAND) and neurodegenerative dementias and the frequency of executive dysfunctions among HIV-positive patients, we evaluated the accuracy of the Frontal Assessment Battery and Clock-Drawing Test together with the Three Questions Test and International HIV Dementia Scale to screen for HAND., Methods: A cross-sectional monocentric study was conducted from 2010 to 2017. The index tests were represented by the four screening tools; the reference standard was represented by a comprehensive neurocognitive battery used to investigate 10 cognitive domains. Patients were screened by a trained infectious diseases physician and those showing International HIV Dementia Scale scores ≤ 10 and/or complaining of neurocognitive symptoms were then evaluated by a trained neuropsychologist., Results: A total of 650 patients were screened and 281 received the full neurocognitive evaluation. HAND was diagnosed in 140 individuals. The sensitivity, specificity, correct classification rate and area under the receiver operating characteristic curve (AUROC) were, respectively, as follows: Frontal Assessment Battery, 40.7%, 95.1%, 68.3% and 0.81; International HIV Dementia Scale, 74.4%, 56.8%, 65.4% and 0.73; Clock-Drawing Test, 30.9%, 73.4%, 53.8% and 0.56; and Three Questions Test, 37.3%, 54.1% and 45.7%. Raising the Frontal Assessment Battery's cut-off to ≤ 16 improved its sensitivity, specificity and correct classification rate to 78.0%, 63.9% and 70.8%, respectively., Conclusions: We observed poor screening performances of the Three Questions and Clock-Drawing Tests. While the International HIV Dementia Scale showed a poor specificity, the Frontal Assessment Battery showed the highest correct classification rate and a promising performance at different exploratory cut-offs., (© 2018 British HIV Association.)
- Published
- 2018
- Full Text
- View/download PDF
215. Evolution of the prevalence of hepatitis C virus infection and hepatitis C virus genotype distribution in human immunodeficiency virus-infected patients in Italy between 1997 and 2015.
- Author
-
Rossetti B, Bai F, Tavelli A, Galli M, Antinori A, Castelli F, Pellizzer G, Cozzi-Lepri A, Bonora S, Monforte AD, Puoti M, and De Luca A
- Subjects
- Adult, Female, HIV, Hepacivirus isolation & purification, Humans, Italy epidemiology, Male, Middle Aged, Prevalence, Prospective Studies, Genotype, HIV Infections complications, Hepacivirus classification, Hepacivirus genetics, Hepatitis C, Chronic epidemiology, Hepatitis C, Chronic virology
- Abstract
Objectives: To analyse the variation of hepatitis C virus (HCV) prevalence and genotype distribution and their determinants in people living with human immunodeficiency virus (HIV) who entered care between 1997 and 2015., Methods: HIV-infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab) were included., Results: Overall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of 12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotypes 1 and 3. The prevalence of HCV infection decreased from 49.2% (2565/5217) during 1997-2002 to 10.2% (556/5466) during 2009-2015. The frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300), whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI 1.04-1.50, p = 0.01), risk category (versus injecting drug users: men who have sex with men AOR 0.01, 95% CI 0.01-0.01, p <0.001; heterosexuals AOR 0.01, 95% CI 0.01-0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01-0.02, p <0.001), being cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85, 95% CI 0.73-0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16-1.80, p = 0.001) and being enrolled in less recent calendar years (versus 1997-2002: 2009-2015 AOR 0.23, 95% CI 0.19-0.27, p <0.001; 2003-2008 AOR 0.49, 95% CI 0.41-0.61, p <0.001)., Conclusions: The prevalence of HCV infection in HIV-infected patients entering into care in Italy significantly declined in more recent calendar years. After adjusting for risk factors and calendar years, HCV co-infection was more frequent in females and in those born in Italy., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
216. Lower dolutegravir plasma concentrations in HIV-positive patients receiving valproic acid.
- Author
-
Palazzo A, Trunfio M, Pirriatore V, Milesi M, De Nicolò A, Alcantarini C, D'Avolio A, Bonora S, Di Perri G, and Calcagno A
- Subjects
- Anticonvulsants administration & dosage, Drug Interactions, Female, HIV Infections complications, HIV Integrase Inhibitors therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Oxazines, Piperazines, Pyridones, Registries, Valproic Acid administration & dosage, Anticonvulsants therapeutic use, HIV Infections drug therapy, HIV Integrase Inhibitors blood, Heterocyclic Compounds, 3-Ring blood, Valproic Acid therapeutic use
- Published
- 2018
- Full Text
- View/download PDF
217. Undetectable antimicrobial plasma concentrations in an HIV-positive patient with protein-losing enteropathy and chylothorax during Mycobacterium genavense and Leishmania abdominal infections.
- Author
-
Motta I, Trunfio M, Calcagno A, Pirriatore V, Scabini S, Palazzo A, Audagnotto S, Fatiguso G, Liberini V, Bellò M, D'Avolio A, Di Perri G, and Bonora S
- Subjects
- Chylothorax diagnosis, Coinfection diagnosis, Humans, Leishmaniasis diagnosis, Lymphoscintigraphy, Male, Middle Aged, Mycobacterium Infections, Nontuberculous diagnosis, Plasma chemistry, Protein-Losing Enteropathies diagnosis, Radiography, Abdominal, Radiography, Thoracic, South America, Tomography, X-Ray Computed, Anti-Infective Agents blood, Chylothorax pathology, Coinfection pathology, HIV Infections complications, Leishmaniasis pathology, Mycobacterium Infections, Nontuberculous pathology, Protein-Losing Enteropathies pathology
- Published
- 2018
- Full Text
- View/download PDF
218. From large to small: the immunohistochemical panel in the diagnosis of early hepatocellular carcinoma.
- Author
-
Vasuri F, Malvi D, Bonora S, Fittipaldi S, Renzulli M, Tovoli F, Golfieri R, Bolondi L, and D'Errico A
- Subjects
- Adult, Aged, Biopsy, Biopsy, Needle, Enhancer of Zeste Homolog 2 Protein analysis, Female, Glutamate-Ammonia Ligase analysis, Glypicans analysis, HSP70 Heat-Shock Proteins analysis, Humans, Immunohistochemistry methods, Male, Middle Aged, Sensitivity and Specificity, Biomarkers, Tumor analysis, Carcinoma, Hepatocellular diagnosis, Liver Neoplasms diagnosis
- Abstract
Aims: The aims of this study were to: validate the use of the immunohistochemical (IHC) markers glutamine synthetase (GS), glypican-3 (GPC3), heat shock protein-70 (HSP70) and enhancer of zeste homologue 2 (EZH2) in liver biopsies for the differential diagnosis between small hepatocellular carcinoma (HCC) and non-neoplastic liver nodules, with special attention to <10-mm nodules; and assess the actual sensitivity and specificity of the single markers, and their combination, in needle biopsies., Methods and Results: One hundred liver nodules, i.e. 66 HCCs and 34 non-neoplastic nodules, were prospectively collected from 43 consecutive orthotopic liver transplantation patients, and subjected to 'backtable' needle biopsies directly on surgical specimens. IHC evaluation was semi-automatically performed with a Benchmark Ultra immunostainer. The morphological and IHC diagnosis in surgical specimens was considered to be the gold standard. GS, GPC3, HSP70 and EZH2 showed 16.6%, 10.7%, 28.8% and 62.1% decreases in sensitivity, respectively, from surgical specimen to needle biopsy. Higher decreases were observed in <10-mm nodules. In 18 HCCs with no morphological diagnostic features of malignancy in biopsies, GPC3 or GS were positive in 16; in seven HCCs, neither morphology nor IHC evaluation ruled out the differential diagnosis made on the basis of needle biopsy., Conclusions: We present for the first time a direct comparison between surgical specimens and needle biopsies to confirm the usefulness and reproducibility of the most widely used antibodies for the diagnosis of small liver nodules. Our results support the use of IHC evaluation in biopsies for the diagnosis of small liver lesions, although the IHC panel could also give negative results in the presence of obvious HCC, and the possibility of false positives should always be considered., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
219. CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose.
- Author
-
Calcagno A, Barco A, Trunfio M, and Bonora S
- Subjects
- AIDS Dementia Complex pathology, Alkynes, Benzoxazines cerebrospinal fluid, Benzoxazines therapeutic use, Brain virology, Cerebrospinal Fluid virology, Cyclopropanes, HIV-1 drug effects, Humans, Neopterin cerebrospinal fluid, Neopterin therapeutic use, Neurocognitive Disorders pathology, Neurocognitive Disorders virology, AIDS Dementia Complex drug therapy, Anti-HIV Agents cerebrospinal fluid, Anti-HIV Agents therapeutic use, Central Nervous System virology, HIV Infections drug therapy, Neurocognitive Disorders drug therapy
- Abstract
Purpose of Review: Neurocognitive disorders are not uncommon in HIV-positive patients but their pathogenesis is multifactorial and incompletely understood. After excluding contributing comorbidities, several factors may impair neurocognition including severe immune suppression, incomplete antiviral efficacy, drugs' persistent immune activation, vascular abnormalities, and drugs' neurotoxicity. The effectiveness of targeted antiretroviral strategies on these risk factors is unknown., Recent Findings: Recent studies support the idea that residual cerebrospinal fluid HIV RNA in the setting of plasma viral suppression is associated with compartmental immune activation but the link to neuronal damage is debated. Some authors have reported an incomplete antiviral efficacy in macrophage-derived cells but targeted antiretroviral regimen switches have not been performed. Additionally, improvements in neurocognition using drugs with better central nervous system penetration or maraviroc (associated with favorable immunological properties) have been observed in pilot studies. Trials evaluating specific interventions for cardiovascular health (including brain white matter abnormalities) and neurotoxicity of antiretrovirals are warranted. Central nervous system-targeted antiretroviral strategies are needed in patients with uncontrolled cerebrospinal HIV replication, and they may be suggested in subjects with low CD4 nadir, individuals carrying drug-resistant viruses, and those with compartmental immune activation.
- Published
- 2018
- Full Text
- View/download PDF
220. The outcome of HIV-positive late presenters according to detectable CMV DNA and anti-CMV treatment.
- Author
-
Bigliano P, Calcagno A, Lucchini A, Audagnotto S, Montrucchio C, Marinaro L, Alcantarini C, Ghisetti V, Di Perri G, and Bonora S
- Subjects
- AIDS-Related Opportunistic Infections immunology, AIDS-Related Opportunistic Infections mortality, AIDS-Related Opportunistic Infections virology, Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes pathology, CD4-Positive T-Lymphocytes virology, Cytomegalovirus genetics, Cytomegalovirus metabolism, Cytomegalovirus Infections immunology, Cytomegalovirus Infections mortality, Cytomegalovirus Infections virology, DNA, Viral antagonists & inhibitors, DNA, Viral metabolism, Female, HIV Infections immunology, HIV Infections mortality, HIV Infections virology, HIV-1 genetics, HIV-1 metabolism, Humans, Male, Middle Aged, Multivariate Analysis, Retrospective Studies, Survival Analysis, Time Factors, Virus Activation drug effects, AIDS-Related Opportunistic Infections drug therapy, Antiviral Agents therapeutic use, Cytomegalovirus drug effects, Cytomegalovirus Infections drug therapy, DNA, Viral genetics, HIV Infections drug therapy, HIV-1 drug effects
- Abstract
Background: HIV late presenters are at high risk of cytomegalovirus (CMV) reactivation and end-organ disease. CMV viraemia has been associated with poor survival but the effect of anti-CMV treatment has not been studied in this setting., Methods: HIV-positive patients were included in a retrospective study if presenting with <350 CD4
+ T-cells/μl and starting an antiretroviral treatment within 3 months of the diagnosis. Primary end point was 5-year survival according to the presence of CMV viraemia, CMV end-organ disease and anti-CMV treatment., Results: 302 patients were included. 157 patients (52%) presented CMV viraemia (CMV-V) and 44 (14.6%) CMV end-organ disease (CMV-EOD). 5-year mortality was higher in CMV-EOD and CMV-V patients than in CMV-negative patients (11.4 versus 9.6 versus 0%; P=0.002). In patients with CMV-V, 5-year mortality was numerically higher in untreated patients (12.9% versus 6.9%; P=0.257) without reaching statistical significance. At univariate analysis the diagnosis of serious opportunistic infections (cryptococcosis, progressive multifocal leukoencephalopathy, lymphoma; P=0.001) and the absence of a negative CMV DNA in the follow-up (P<0.001) were associated with poor outcome. At multivariate analysis HCV coinfection (P=0.016; aOR 6.98, 95% CI 1.50, 32.59), the absence of a negative CMV DNA in the follow-up (P<0.001; aOR 19.40, 95% CI 3.70, 101.64) and marginally the absence of anti-CMV treatment (P=0.052; aOR 4.944, 95% CI 0.99, 24.73) were independent predictors of poor outcome., Conclusions: CMV reactivation in HIV-positive patients with poor immunity is associated with worse prognosis: the pre-emptive use of anti-CMV therapy was associated with a better outcome in patients with CMV-V.- Published
- 2018
- Full Text
- View/download PDF
221. Pharmacokinetics and pharmacogenetics of anti-tubercular drugs: a tool for treatment optimization?
- Author
-
Motta I, Calcagno A, and Bonora S
- Subjects
- Animals, Antitubercular Agents adverse effects, Antitubercular Agents pharmacokinetics, Dose-Response Relationship, Drug, Drug Monitoring methods, Drug Resistance, Bacterial, Humans, Isoniazid administration & dosage, Isoniazid pharmacokinetics, Models, Biological, Rifampin administration & dosage, Rifampin pharmacokinetics, Tuberculosis genetics, Antitubercular Agents administration & dosage, Pharmacogenetics, Tuberculosis drug therapy
- Abstract
Introduction: WHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Areas covered: This review discusses available pharmacokinetic and pharmacogenetic data of first and second-line antitubercular agents in relation to efficacy and toxicity. Pharmacodynamic implications of optimized drugs and new options regimens are reviewed. Moreover a specific session describes innovative investigations on drug penetration. Expert opinion: The optimal use of available antitubercular drugs is paramount for tuberculosis control and eradication. Whilst trials are still on-going, higher rifampicin doses should be reserved to treatment for tubercular meningitis. Therapeutic Drug Monitoring with limiting sampling strategies is advised in patients at risk of failure or with slow treatment response. Further studies are needed in order to provide definitive recommendations of pharmacogenetic-based individualization: however lower isoniazid doses in NAT2 slow acetylators and higher rifampicin doses in individuals with SLCO1B1 loss of function genes are promising strategies. Finally in order to inform tailored strategies we need more data on tissue drug penetration and pharmacological modelling.
- Published
- 2018
- Full Text
- View/download PDF
222. Socioeconomic status and biomedical risk factors in migrants and native tuberculosis patients in Italy.
- Author
-
Pittalis S, Piselli P, Contini S, Gualano G, Alma MG, Tadolini M, Piccioni P, Bocchino M, Matteelli A, Bonora S, Di Biagio A, Franzetti F, Carbonara S, Gori A, Sotgiu G, Palmieri F, Ippolito G, and Girardi E
- Subjects
- Adult, Aged, Chronic Disease, Comorbidity, Cross-Sectional Studies, Female, Humans, Incidence, Italy, Male, Middle Aged, Poverty, Prevalence, Risk Factors, Socioeconomic Factors, Young Adult, Social Class, Transients and Migrants, Tuberculosis diagnosis, Tuberculosis epidemiology
- Abstract
Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18-64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31-53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent.
- Published
- 2017
- Full Text
- View/download PDF
223. Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients.
- Author
-
Focà E, Calcagno A, Bonito A, Simiele M, Domenighini E, D'Avolio A, Quiros Roldan E, Trentini L, Casari S, Di Perri G, Castelli F, and Bonora S
- Subjects
- Adult, Atazanavir Sulfate adverse effects, Atazanavir Sulfate therapeutic use, CD4 Lymphocyte Count, Chromatography, High Pressure Liquid, Drug Therapy, Combination, Emtricitabine therapeutic use, Female, HIV Infections metabolism, HIV Infections virology, HIV Protease Inhibitors blood, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, Humans, Infant, Newborn, Leukocytes, Mononuclear chemistry, Pregnancy, Pregnancy Complications, Infectious metabolism, Pregnancy Complications, Infectious virology, Pregnancy Trimesters metabolism, Prospective Studies, RNA, Viral blood, Ritonavir administration & dosage, Ritonavir therapeutic use, Tenofovir therapeutic use, Viral Load, Atazanavir Sulfate administration & dosage, Atazanavir Sulfate pharmacokinetics, HIV Infections drug therapy, HIV Protease Inhibitors administration & dosage, HIV Protease Inhibitors pharmacokinetics, Pregnancy Complications, Infectious drug therapy
- Abstract
Background: Atazanavir (300 mg) boosted by ritonavir (100 mg) is the preferred third drug in pregnancy. However, there is still discordance on atazanavir dose increase during the third trimester., Objectives: To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery., Methods: This was an observational study. HIV-infected pregnant patients treated with atazanavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine had been prospectively enrolled after having signed a written informed consent form. Plasma and intracellular atazanavir and ritonavir Ctrough (24 ± 3 h after drug intake) were measured at each visit during the first, second and third trimesters and post-partum using validated HPLC-MS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests., Results: Twenty-five patients were enrolled; at baseline, the median age was 32 years (27-35). All patients had plasma HIV RNA <50 copies/mL; the median CD4+ count was 736 cells/mm3 (542-779). Atazanavir plasma concentrations were 441 ng/mL (261-1557), 710 ng/mL (338-1085), 556 ng/mL (334-1022) and 837 ng/mL (608-1757) during the first, second and third trimesters and post-partum, respectively; intracellular concentrations were 743 ng/mL (610-1928), 808 ng/mL (569-1620), 756 ng/mL (384-1074) and 706 ng/mL (467-2688), respectively. Atazanavir intracellular/plasma ratios were 1.32 (0.98-2.77), 1.34 (1.13-1.88), 1.38 (0.61-2.63) and 1.07 (0.56-2.69), respectively. Atazanavir intracellular concentrations and intracellular/plasma ratios showed non-significant changes over time (P > 0.05)., Conclusions: This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100 mg atazanavir/ritonavir dosing throughout pregnancy., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
224. Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?
- Author
-
Mornese Pinna S, Scarvaglieri E, Milia MG, Imperiale D, Ghisetti V, Audagnotto S, Prochet A, Lipani F, Bonora S, Di Perri G, and Calcagno A
- Subjects
- AIDS-Related Opportunistic Infections complications, Adult, Brain Diseases complications, Brain Diseases pathology, Female, HIV Infections complications, HIV-1, Humans, JC Virus, Leukoencephalopathy, Progressive Multifocal virology, Male, Middle Aged, Polyomavirus Infections pathology, Retrospective Studies, AIDS-Related Opportunistic Infections virology, Brain Diseases virology, DNA, Viral cerebrospinal fluid, HIV Infections virology, Polyomavirus Infections complications
- Abstract
In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.
- Published
- 2017
- Full Text
- View/download PDF
225. miRNA Signature of Hepatocellular Carcinoma Vascularization: How the Controls Can Influence the Signature.
- Author
-
Fittipaldi S, Vasuri F, Bonora S, Degiovanni A, Santandrea G, Cucchetti A, Gramantieri L, Bolondi L, and D'Errico A
- Subjects
- Aged, Aged, 80 and over, Animals, Biomarkers, Tumor biosynthesis, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Disease Progression, Female, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, MicroRNAs biosynthesis, Middle Aged, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic pathology, Retrospective Studies, Biomarkers, Tumor genetics, Carcinoma, Hepatocellular genetics, Gene Expression Regulation, Neoplastic, Liver Neoplasms genetics, MicroRNAs genetics, Neovascularization, Pathologic genetics
- Abstract
Background: miRNA deregulation and vascular modifications constitute promising predictors in the study of hepatocellular carcinoma (HCC). In the literature, the relative miRNA abundance in HCC is usually determined using as control non-matched tumoral tissue, healthy liver, or cirrhotic liver. However, a common standard RNA control for the normalization toward the tissue gene expression was not settled yet., Aim: To assess the differences existing in the quantitative miRNA gene expression in HCC on tissue according to two different liver controls., Methods: A wide array of miRNAs was analyzed on 22 HCCs arisen in cirrhotic and non-cirrhotic livers by means of microfluidic cards. Control samples included total RNA extracted from healthy and cirrhotic livers. Immunohistochemistry for CD34 and Nestin was performed to assess the pattern of intratumoral vascular modifications., Results: Six miRNAs were deregulated in HCCs using either controls: miR-532, miR-34a, miR-93, miR-149#, miR-7f-2#, and miR-30a-5p. Notably, the miRNA expression changed significantly between HCCs arisen in cirrhotic and non-cirrhotic livers, according to the control used for normalization. Different miRNA profiles were found also in HCCs with different vascular patterns, according to the control used for normalization., Conclusions: Our data confirm that the choice of the methodology, and particularly the control used for normalization, represents the main concern in miRNA evaluation, particularly in a heterogeneous model such as liver pathology. Still we observed the deregulation of some common miRNAs as promising in HCC cancerogenesis and progression. A standardized control will be a crucial achievement to compare miRNA expression among different laboratories.
- Published
- 2017
- Full Text
- View/download PDF
226. Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL.
- Author
-
Madeddu G, Rusconi S, Cozzi-Lepri A, Di Giambenedetto S, Bonora S, Carbone A, De Luca A, Gianotti N, Di Biagio A, and Antinori A
- Subjects
- Adult, Anti-HIV Agents adverse effects, Cohort Studies, Darunavir adverse effects, Drug Therapy, Combination adverse effects, Female, HIV-1 genetics, Humans, Italy, Male, Middle Aged, RNA, Viral genetics, Raltegravir Potassium adverse effects, Ritonavir adverse effects, Anti-HIV Agents therapeutic use, Darunavir therapeutic use, HIV Infections drug therapy, Raltegravir Potassium therapeutic use, Ritonavir therapeutic use, Viral Load
- Abstract
Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens., Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting., Study Design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan-Meier curves and Cox regression models were performed to estimate time to event probability., Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9-31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1-13%] by 12 and 9% (95% CI 2-16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1-17%) and 22% (95% CI 11-33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01-0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25-0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6-779; p = 0.004)., Conclusions: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.
- Published
- 2017
- Full Text
- View/download PDF
227. PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.
- Author
-
Di Biagio A, Riccardi N, Signori A, Maserati R, Nozza S, Gori A, Bonora S, Borderi M, Ripamonti D, Rossi MC, Orofino G, Quirino T, Nunnari G, Celesia BM, Martini S, Sagnelli C, Mazzola G, Colletti P, Bartolozzi D, Bini T, Ladisa N, Castelnuovo F, Saracino A, and Lo Caputo S
- Subjects
- Anti-HIV Agents adverse effects, Anti-HIV Agents economics, Cross-Sectional Studies, HIV Infections economics, Humans, Italy, Risk, Surveys and Questionnaires, Anti-HIV Agents therapeutic use, HIV Infections prevention & control, Health Knowledge, Attitudes, Practice, Physicians psychology, Pre-Exposure Prophylaxis economics
- Abstract
Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.
- Published
- 2017
- Full Text
- View/download PDF
228. Prevalence and predictors of long corrected QT interval in HIV-positive patients: a multicenter study.
- Author
-
Gili S, Mancone M, Ballocca F, Grosso Marra W, Calcagno A, D'Ettorre G, Cannillo M, D'Ascenzo F, Orofino G, Marruncheddu L, Lonni E, Cinque A, Vullo F, Ceccarelli G, Vilardi I, Sardella G, Vullo V, Moretti C, Fedele F, Bonora S, and Gaita F
- Subjects
- Action Potentials, Adult, Aged, Antiretroviral Therapy, Highly Active, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac physiopathology, CD4 Lymphocyte Count, Chi-Square Distribution, Electrocardiography, Female, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections immunology, Humans, Italy epidemiology, Logistic Models, Male, Middle Aged, Multivariate Analysis, Prevalence, Retrospective Studies, Risk Factors, Time Factors, Arrhythmias, Cardiac epidemiology, HIV Infections epidemiology, Heart Conduction System physiopathology, Heart Rate
- Abstract
Aims: HIV and highly active antiretroviral therapy (HAART) may affect cardiac conduction, and a higher incidence of sudden death has been recognized in HIV-positive patients. Nevertheless, predictors of prolonged corrected QT interval (cQT) have been poorly described. The aim of the study was to investigate the prevalence and predictors of long cQT in a cohort of HIV-positive patients., Methods: Consecutive HIV-positive patients followed in a primary prevention clinic at two Italian institutions were retrospectively enrolled. A 12-lead ECG was recorded in all patients; main clinical features were collected. Prevalence of long cQT (defined as cQT >470 ms in women and >450 ms in men) was the primary end-point. Secondary end-points were the identification of predictors of cQT prolongation, and the association between HAART and HIV-related features with long cQT., Results: Three hundred and fifty-one HIV-positive patients were included, 26 (7.4%) with long cQT. Mean age was higher among those with long cQT (51.6 vs. 57.6 years; P = 0.007). A higher prevalence of long cQT was reported for patients with a CD4+ cell count below 200 cells/μl at the moment of ECG (60 vs. 24.2%; P = 0.002) and with a nadir of CD4+ cell count below 200 cells/μl (91.3 vs. 58.6%; P = 0.001). At multivariate analysis, only the nadir of CD4+ cell count below 200 cells/μl consistently related to the presence of long cQT (odds ratio 5.8, 95% confidence interval 1.3-26.4)., Conclusion: A low CD4+ cell count is associated with long cQT independently from HAART in HIV-positive patients and may be useful to correctly stratify arrhythmic risk in these patients.
- Published
- 2017
- Full Text
- View/download PDF
229. Role of vitamin D pathway gene polymorphisms on rifampicin plasma and intracellular pharmacokinetics.
- Author
-
Allegra S, Fatiguso G, Calcagno A, Baietto L, Motta I, Favata F, Cusato J, Bonora S, Di Perri G, and D'Avolio A
- Subjects
- Adult, Alleles, Female, Genotype, Humans, Liver-Specific Organic Anion Transporter 1 genetics, Male, Middle Aged, Plasma metabolism, Retrospective Studies, Polymorphism, Single Nucleotide genetics, Rifampin blood, Rifampin pharmacokinetics, Vitamin D genetics
- Abstract
Aim: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations., Patients & Methods: Rifampicin C
max and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction., Results: Twenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells Cmax , remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma Cmax regression model., Conclusion: This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.- Published
- 2017
- Full Text
- View/download PDF
230. Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure.
- Author
-
Calcagno A, Pagani N, Ariaudo A, Arduino G, Carcieri C, D'Avolio A, Marinaro L, Tettoni MC, Trentini L, Di Perri G, and Bonora S
- Subjects
- Adult, Atazanavir Sulfate blood, Atazanavir Sulfate therapeutic use, Darunavir blood, Darunavir therapeutic use, Drug Therapy, Combination, Female, Follow-Up Studies, HIV Infections virology, HIV Protease Inhibitors therapeutic use, HIV-1 isolation & purification, Humans, Lopinavir blood, Lopinavir therapeutic use, Male, Medication Adherence, Middle Aged, RNA, Viral blood, Registries, Regression Analysis, Retrospective Studies, Ritonavir therapeutic use, Treatment Failure, Drug Monitoring, HIV Infections drug therapy, HIV Protease Inhibitors blood, Ritonavir blood, Viral Load
- Abstract
Background: Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure., Methods: A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards., Results: The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P < 0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P = 0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P < 0.001), genotypic susceptibility score ≤2 ( P = 0.001), lower nadir CD4 cell count ( P = 0.003) and not being in the adherent group ( P = 0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks., Conclusions: The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
231. UPLC-MS/MS method for the simultaneous quantification of three new antiretroviral drugs, dolutegravir, elvitegravir and rilpivirine, and other thirteen antiretroviral agents plus cobicistat and ritonavir boosters in human plasma.
- Author
-
Simiele M, Ariaudo A, De Nicolò A, Favata F, Ferrante M, Carcieri C, Bonora S, Di Perri G, and De Avolio A
- Subjects
- Anti-HIV Agents blood, Anti-HIV Agents chemistry, Cobicistat blood, Cobicistat chemistry, Heterocyclic Compounds, 3-Ring blood, Heterocyclic Compounds, 3-Ring chemistry, Humans, Limit of Detection, Oxazines, Piperazines, Pyridones, Quinolones blood, Quinolones chemistry, Reproducibility of Results, Rilpivirine blood, Rilpivirine chemistry, Ritonavir blood, Ritonavir chemistry, Anti-Retroviral Agents blood, Anti-Retroviral Agents chemistry, Chromatography, High Pressure Liquid methods, Tandem Mass Spectrometry methods
- Abstract
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs. In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma. One hundred microliters of plasma samples were added with internal standard (6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline), underwent a simple protein precipitation with methanol:acetonitrile (50:50v/v) followed by sample dilution with water. Chromatographic separation was performed on a Acquity
® UPLC HSS T3 column (150mm x 2.1mm I.D) with a particle size of 1.8μm and compounds were detected with a tandem mass detector, monitoring two ion transitions for each drugs. The mean recovery of RPV, DTG and EVG were 101%, 87% and 112.3% respectively. Accuracy and precision inter/intra-day were below 15% for all drugs, in accordance to Food and Drug Administration guidelines requirements. The UPLC-MS/MS method reported here could be used routinely to monitor plasma concentrations of antiviral drugs, including RPV, DTG and EVG., (Copyright © 2017. Published by Elsevier B.V.)- Published
- 2017
- Full Text
- View/download PDF
232. Pharmacokinetics of first-line antitubercular drugs in plasma and PBMCs.
- Author
-
Motta I, Calcagno A, Baietto L, Bigliano P, Costa C, Baruffi K, Fatiguso G, D'Avolio A, Di Perri G, and Bonora S
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Antitubercular Agents blood, Antitubercular Agents pharmacokinetics, Leukocytes, Mononuclear metabolism, Tuberculosis blood
- Published
- 2017
- Full Text
- View/download PDF
233. Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs.
- Author
-
Calcagno A, Cusato J, D'Avolio A, and Bonora S
- Subjects
- Animals, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, Anti-Retroviral Agents therapeutic use, Drug Interactions physiology, HIV Infections drug therapy, Humans, Polymorphism, Genetic drug effects, Tissue Distribution drug effects, Tissue Distribution physiology, Anti-Retroviral Agents pharmacokinetics, HIV Infections genetics, HIV Infections metabolism, Polymorphism, Genetic genetics
- Abstract
Background: Antiretroviral treatment is highly effective in enhancing HIV-positive patients' survival and quality of life. Despite an increased tolerability in recent years, a substantial amount of patients experience side effects. Antiretrovirals' efficacy and tolerability have been associated with plasma concentrations and single nucleotide polymorphisms in selected genes involved in drug disposition., Objective: Our aim was to review the current knowledge in genetic polymorphisms affecting plasma, intracellular or compartmental concentrations of antiretrovirals., Methods: A search of the PubMed database was conducted to identify relevant articles, using the following terms: 'pharmacogenetics' or 'pharmacogenomics' or 'single nucleotide polymorphisms' or 'genetic/allelic variants' and 'pharmacokinetics' or 'concentrations' and 'HIV' or 'antiretroviral'. Abstracts from the main HIV conferences during 2015 and 2016 were also searched using the same keywords. Abstracts were manually checked and, if relevant, full papers were obtained. Only articles published in English were selected., Results: Several genetic polymorphisms in genes coding enzymes involved in drug metabolism (cytochrome P450 isoenzymes and uridine diphosphate glucuronosyltransferases) and transport (P-glycoprotein, anionic and cationic transporters, other transporters), as well as nuclear receptors (pregnane X receptor and the constitutive androstane receptor), have been associated with concentrations of antiretrovirals. The extent of such influence, the conflicting data, and the potential clinical relevance are discussed in the main section of this article., Conclusion: Genetic polymorphisms may affect antiretroviral disposition, as well as both efficacy and toxicity. Despite a large amount of data, such precious knowledge has seldom been applied in patients. Studies on the clinical relevance and cost effectiveness of tailoring antiretroviral regimens to patients' genetic assets are lacking, but their importance may grow with the increasing age and complexity of persons living with HIV/AIDS.
- Published
- 2017
- Full Text
- View/download PDF
234. Pupil segmentation adaptive optics for invivo mouse retinal fluorescence imaging.
- Author
-
Wahl DJ, Huang C, Bonora S, Jian Y, and Sarunic MV
- Abstract
Adaptive Optics (AO) for scanning laser ophthalmoscopy enables high-resolution retinal imaging that can be used for preclinical research of diseases causing vision loss. Pupil Segmentation (PS) is an approach to wavefront-sensorless AO that acquires images within subregions across the imaging pupil to measure the wavefront slopes at the corresponding locations of the beam. We present PS-AO as an approach to correct ocular aberrations in ∼7 s, implemented to minimize respiratory motion from an anesthetized mouse. We demonstrated an improvement in resolution and an image intensity increase of ∼25% across all results using PS-AO for in vivo fluorescence retinal imaging in mice using a MEMS-based segmented deformable mirror.
- Published
- 2017
- Full Text
- View/download PDF
235. Wavefront sensorless adaptive optics OCT with the DONE algorithm for in vivo human retinal imaging [Invited].
- Author
-
Verstraete HRGW, Heisler M, Ju MJ, Wahl D, Bliek L, Kalkman J, Bonora S, Jian Y, Verhaegen M, and Sarunic MV
- Abstract
In this report, which is an international collaboration of OCT, adaptive optics, and control research, we demonstrate the Data-based Online Nonlinear Extremum-seeker (DONE) algorithm to guide the image based optimization for wavefront sensorless adaptive optics (WFSL-AO) OCT for in vivo human retinal imaging. The ocular aberrations were corrected using a multi-actuator adaptive lens after linearization of the hysteresis in the piezoelectric actuators. The DONE algorithm succeeded in drastically improving image quality and the OCT signal intensity, up to a factor seven, while achieving a computational time of 1 ms per iteration, making it applicable for many high speed applications. We demonstrate the correction of five aberrations using 70 iterations of the DONE algorithm performed over 2.8 s of continuous volumetric OCT acquisition. Data acquired from an imaging phantom and in vivo from human research volunteers are presented.
- Published
- 2017
- Full Text
- View/download PDF
236. Pharmacokinetics of dolutegravir and rilpivirine in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus-coinfected patients with liver cirrhosis.
- Author
-
Merli M, Galli L, Marinaro L, Ariaudo A, Messina E, Uberti-Foppa C, Castagna A, D'Avolio A, Lazzarin A, Bonora S, and Hasson H
- Subjects
- Coinfection drug therapy, Coinfection virology, Drug Therapy, Combination, Female, Genotype, HIV Infections complications, Hepacivirus physiology, Hepatitis C, Chronic complications, Heterocyclic Compounds, 3-Ring administration & dosage, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Liver Cirrhosis virology, Liver Transplantation, Male, Middle Aged, Oxazines, Piperazines, Prospective Studies, Pyridones, RNA, Viral blood, Rilpivirine administration & dosage, Rilpivirine therapeutic use, Simeprevir administration & dosage, Simeprevir therapeutic use, Sofosbuvir administration & dosage, Sofosbuvir therapeutic use, Viral Load, HIV Infections drug therapy, Hepatitis C, Chronic drug therapy, Heterocyclic Compounds, 3-Ring pharmacokinetics, Liver Cirrhosis complications, Rilpivirine pharmacokinetics, Simeprevir pharmacokinetics, Sofosbuvir pharmacokinetics
- Abstract
Objectives: To evaluate the plasma trough concentrations ( C trough ) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed., Patients and Methods: A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted. Dolutegravir, rilpivirine, GS-331007 (sofosbuvir metabolite) and simeprevir C trough were evaluated with a validated HPLC method at anti-HCV treatment baseline and weeks 2 and 4. Geometric means were calculated to summarize C trough values., Results: Twelve patients were evaluated: 75% were males and the median (IQR) age was 53 (53-55) years. All patients were Child-Pugh stage A, except one who was stage B. The geometric mean (95% CI) of C trough of rilpivirine and dolutegravir did not change between baseline and week 4 ( P = 0.654 and P = 0.268, respectively), with corresponding overall values of 135 (102-177) and 1357 (970-1897) ng/mL. The overall geometric mean (95% CI) of GS-331007 and simeprevir C trough was 370 (268-512) and 2537 (1569-4101) ng/mL, respectively, without significant variation between weeks 2 and 4 ( P = 0.643 and P = 0.179, respectively). All patients completed anti-HCV treatment, achieving sustained virological response. All but two patients maintained undetectable HIV-RNA up to post-treatment week 24., Conclusions: Dolutegravir and rilpivirine C trough appeared not to be affected by concomitant treatment with simeprevir plus sofosbuvir in these HIV/HCV-coinfected patients with liver cirrhosis, supporting the use of this antiretroviral regimen in this setting., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
237. Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen.
- Author
-
Armenia D, Di Carlo D, Calcagno A, Vendemiati G, Forbici F, Bertoli A, Berno G, Carta S, Continenza F, Fedele V, Bellagamba R, Cicalini S, Ammassari A, Libertone R, Zaccarelli M, Ghisetti V, Andreoni M, Ceccherini-Silberstein F, Bonora S, Di Perri G, Antinori A, Perno CF, and Santoro MM
- Subjects
- Adult, Anti-HIV Agents administration & dosage, Deoxycytidine therapeutic use, Drug Combinations, Emtricitabine administration & dosage, Female, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, Humans, Male, Middle Aged, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Rilpivirine administration & dosage, Tablets, Tenofovir administration & dosage, Anti-HIV Agents therapeutic use, Emtricitabine therapeutic use, HIV Infections drug therapy, Rilpivirine therapeutic use, Tenofovir therapeutic use, Viral Load drug effects
- Abstract
Objectives: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes)., Methods: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated., Results: Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression., Conclusions: TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
238. Blood Brain Barrier Impairment in HIV-Positive Naïve and Effectively Treated Patients: Immune Activation Versus Astrocytosis.
- Author
-
Calcagno A, Romito A, Atzori C, Ghisetti V, Cardellino C, Audagnotto S, Scarvaglieri E, Lipani F, Imperiale D, Di Perri G, and Bonora S
- Subjects
- Adult, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Blood-Brain Barrier drug effects, Blood-Brain Barrier immunology, Cross-Sectional Studies, Female, Gliosis immunology, HIV Infections immunology, HIV-1 drug effects, Humans, Immunity, Cellular drug effects, Male, Middle Aged, Treatment Outcome, Blood-Brain Barrier metabolism, Gliosis cerebrospinal fluid, HIV Infections cerebrospinal fluid, HIV Infections drug therapy, HIV-1 metabolism, Immunity, Cellular physiology
- Abstract
Blood brain barrier (BBB) damage is a common feature in central nervous system infections by HIV and it may persist despite effective antiretroviral therapy. Astrocyte involvement has not been studied in this setting. Patients were enrolled in an ongoing prospective study and subjects with central nervous system-affecting disorders were excluded. Patients were divided into two groups: treated subjects with cerebrospinal fluid (CSF) HIV RNA <50 copies/mL (CSF-controllers) and in late-presenters CD4+ T lymphocytes <100/uL. CSF biomarkers of neuronal or astrocyte damage were measured and compared to CSF serum-to-albumin ratio. 134 patients were included; 67 subjects in each group (50 %) with similar demographic characteristics (with the exception of older age in CSF controllers). CD4 (cells/uL), plasma and CSF HIV RNA (Log
10 copies/mL) were 43 (20-96), 5.6 (5.2-6) and 3.9 (3.2-4.7) in LPs and 439 (245-615), <1.69 (9 patients <2.6) and <1.69 in CSFc. BBB impairment was observed in 17 late-presenters (25.4 %) and in 9 CSF-controllers (13.4 %). CSF biomarkers were similar but for higher CSF neopterin values in late-presenters (2.3 vs. 0.6 ng/mL, p < 0.001). CSARs were associated with CSF neopterin (rho = 0.31, p = 0.03) and HIV RNA (rho = 0.24, p = 0.05) in late-presenters and with CSF tau (rho = 0.51, p < 0.001), p-tau (rho = 0.47, p < 0.001) and S100beta (rho = 0.33, p = 0.009) in CSF-controllers. In HAART-treated subjects with suppressed CSF HIV RNA, BBB altered permeability was associated with markers of neuronal damage and astrocytosis. Additional treatment targeting astrocytosis and/or viral protein production might be needed in order to reduce HIV effects in the central nervous system.- Published
- 2017
- Full Text
- View/download PDF
239. Efficacy, safety and pharmacokinetics of atazanavir (200mg twice daily) plus raltegravir (400mg twice daily) dual regimen in the clinical setting.
- Author
-
Marinaro L, Calcagno A, Ripamonti D, Cenderello G, Pirriatore V, Trentini L, Salassa B, Bramato C, Orofino G, D'Avolio A, Rizzi M, Di Perri G, Rusconi S, and Bonora S
- Subjects
- Adult, Anti-HIV Agents pharmacokinetics, Atazanavir Sulfate pharmacokinetics, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections virology, HIV-1 genetics, Humans, Male, Middle Aged, Mutation, Missense, Plasma chemistry, Raltegravir Potassium pharmacokinetics, Retrospective Studies, Selection, Genetic, Treatment Outcome, Viral Load, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Atazanavir Sulfate administration & dosage, Atazanavir Sulfate adverse effects, HIV Infections drug therapy, Raltegravir Potassium administration & dosage, Raltegravir Potassium adverse effects
- Abstract
Background: Unboosted atazanavir with raltegravir has been investigated at 300mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations., Objectives: Atazanavir 200mg twice daily could increase tolerability and plasma exposure., Study Design: Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated., Results: 102 patients [72.5% male, age 46.4 years (42-54), BMI 24kg/m
2 (22-26)] were included. CD4+ T lymphocytes were 417 cell/μL (302-704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n=67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60ml/min (n=27) had no significant changes while patients with eCRCL >60ml/min showed significant decrease (-9.8ml/min, p=0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321ng/mL (147-720) and 412ng/mL (225-695). Self-reported non-adherence (n=4) was significantly associated with virological failure (p=0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p=0.07)., Discussion: Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs' plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression., (Copyright © 2016 Elsevier B.V. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
240. Treating HIV Infection in the Central Nervous System.
- Author
-
Calcagno A, Di Perri G, and Bonora S
- Subjects
- Central Nervous System drug effects, Humans, AIDS Dementia Complex drug therapy, AIDS Dementia Complex virology, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Central Nervous System virology, HIV-1 drug effects
- Abstract
Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management. In this review, the penetration of drugs into the cerebrospinal fluid/CNS is discussed as well as the viral and clinical consequences associated with higher/lower compartmental exposure. We also review the potential interventions according to the currently identified underlying mechanisms, including persistent CNS immune activation, legacy effects, low-level viral replication and escape, co-morbidities, and antiretroviral-associated direct and indirect 'neurotoxicity'. Adjunctive therapies and interventions (including neuro-rehabilitation) are then briefly discussed. The treatment of HIV infection in the CNS is a complex area of therapeutics requiring multidisciplinary interventions and further study.
- Published
- 2017
- Full Text
- View/download PDF
241. High Incidence of Infections in HIV-positive Patients Treated for Lymphoproliferative Disorders.
- Author
-
Calcagno A, Lucchini A, Caracciolo D, Balbiano R, Bracchi M, Sordella F, Gregori G, Lipani F, Audagnotto S, Chiriotto M, Cavaglia G, Ghisetti V, Di Perri G, and Bonora S
- Subjects
- AIDS-Related Opportunistic Infections etiology, Adult, Animals, Bacteria classification, Bacteria isolation & purification, Female, Fungi classification, Fungi isolation & purification, Humans, Incidence, Male, Middle Aged, Parasites classification, Parasites isolation & purification, Retrospective Studies, Survival Analysis, Viruses classification, Viruses isolation & purification, AIDS-Related Opportunistic Infections epidemiology, AIDS-Related Opportunistic Infections mortality, Antineoplastic Agents therapeutic use, HIV Infections complications, Lymphoproliferative Disorders complications, Lymphoproliferative Disorders drug therapy
- Abstract
Background: Lymphoproliferative disorders are frequently diagnosed in HIV-positive patients and severe infections may occur during antineoplastic treatments: the incidence and impact of such events are not well-characterized., Objective: To describe the occurrence and mortality of incident infections in HIV-positive individuals treated for lymphoproliferative disorders., Methods: A retrospective study in HIV-positive adults with lymphoproliferative disorders (2000- 2012) who were hospitalised to receive antineoplastic chemotherapy; antimicrobial prophylaxis with alternate day co-trimoxazole (800/160 mg) was administered to all individuals., Results: 103 patients were included: mostly males (81, 78.6%), Caucasians (101, 98.1%), with a median age of 43 years (39-51). Fifty-eight (56.3%) patients had non-Hodgkin's lymphoma (NHL), thirty-two (29.1%) had Hodgkin's lymphoma (HL) and ten patients (9.7%) had Burkitt's lymphoma (BL). Five year survival was 63.1%: the best survival rates were reported in HL (78.1%), followed by NHL (58.6%) and BL (50%). Forty-four patients (42.7%) developed 82 infections during follow up: identified causative agents were bacteria (35, 42.7%), viruses (28, 34.1%), mycobacteria (7, 8.5%), protozoa (7, 8.5%) and fungi (5, 6.1%). Cytomegalovirus infections (n=17, including 5 endorgan diseases) emerged 53 days after the diagnosis: multivariate analysis showed CD4+ cell count <100/uL as the only independently associated factor (p<0.001, aOR=23.5). Two factors were associated with mortality risk: an IPI/IPS-score of >2 (p=0.004, aOR=6.55) and the presence of CMV disease (p=0.032, aOR=2.73)., Conclusion: HIV positive patients receiving treatment for lymphoproliferative disorders suffer from a high incidence of infections and associated mortality risk. Tailored prophylactic strategies need to be considered in this setting., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2017
- Full Text
- View/download PDF
242. Cerebrospinal fluid viral load and neopterin in HIV-positive patients with undetectable viraemia.
- Author
-
Motta I, Allice T, Romito A, Ferrara M, Ecclesia S, Imperiale D, Ghisetti V, Di Perri G, Bonora S, and Calcagno A
- Subjects
- Adult, Antiretroviral Therapy, Highly Active, Biomarkers, CD4 Lymphocyte Count, Female, HIV Infections diagnosis, HIV Infections drug therapy, Humans, Male, Middle Aged, RNA, Viral, Cerebrospinal Fluid virology, HIV Infections cerebrospinal fluid, HIV Infections virology, Neopterin cerebrospinal fluid, Viral Load, Viremia
- Abstract
Background: Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. The aim of this study was to analyse the prevalence and predictors of non-detectable CSF HIV RNA using a commercial assay., Methods: In adult HIV-positive HAART-treated patients with confirmed plasma HIV RNA <50 copies/ml, CSF HIV RNA (with Roche Amplicor Assay) and neopterin were measured., Results: 112 adult patients were included. Plasma and CSF HIV RNA were non-detectable (target not detected [TND]) in 29 (25.9%) and 36 (32.1%) patients, respectively. CSF TND was observed more frequently in patients with plasma TND (P=0.005, OR=3.87). CSF neopterin levels were associated with age (rho =0.333, P=0.002) and current (rho= -0.272, P=0.015) and nadir (rho =-0.240, P=0.038) CD4
+ T-lymphocytes; the lowest CSF neopterin concentration was observed in patients with CSF TND versus other viral load strata (0.62 mg/dl versus 0.78 mg/dl; P=0.048)., Conclusions: Efficaciously treated HIV-positive patients with detectable plasma HIV RNA might imperfectly control CSF viral replication. Prospective studies addressing the management and neurocognitive consequences of CSF low-level viraemia are warranted.- Published
- 2017
- Full Text
- View/download PDF
243. Use of Daclatasvir in HCV/HIV-Coinfected Patients in a Real-Life Setting.
- Author
-
Bonora S and Puoti M
- Subjects
- Carbamates, Coinfection virology, Drug Interactions, Genotype, HIV Infections virology, Hepatitis C, Chronic virology, Humans, Imidazoles adverse effects, Pyrrolidines, Valine analogs & derivatives, Antiviral Agents therapeutic use, Coinfection drug therapy, HIV Infections drug therapy, Hepatitis C, Chronic drug therapy, Imidazoles therapeutic use, Viral Nonstructural Proteins antagonists & inhibitors
- Abstract
The burden of HIV and HCV coinfection is estimated to affect 5-7 million people worldwide, with approximately 15-30% of people with HIV coinfected with HCV. The first oral direct-acting antivirals have shown to improve the response in patients with HIV/HCV coinfection, and more recently, other direct-acting antivirals that target various stages of the HCV life cycle have been developed, among them daclatasvir. The objective of this article is to examine recent clinical studies investigating the efficacy and safety of daclatasvir in comparison with other antiretroviral drugs, focusing on its efficacy in the coinfected HIV patient and real-life data. Daclatasvir is a direct-acting antiviral first-in-class HCV NS5A replication complex inhibitor, approved in June 2014 by the European Medicines Agency for use in combination with other medicinal products for the treatment of chronic HCV infection in adults, and in July 2015 by the Food and Drug Administration. Its efficacy was demonstrated in several trials, with a mean sustained virologic response 12 weeks after therapy completion above 90%. The majority of adverse events related to treatment were mild-to-moderate in severity, with no discontinuation of therapy because of an adverse event and no clinically significant interactions with most of HIV antiretrovirals. The efficacy of daclatasvir in HIV/HCV-coinfected patients was demonstrated in many studies, and confirmed by real-life data for patients with different genotypes, patients with cirrhosis, and in association with ribavirin, opening a new frontier in the treatment of these patients.
- Published
- 2017
244. Comparative safety and efficacy of statins for primary prevention in human immunodeficiency virus-positive patients: a systematic review and meta-analysis.
- Author
-
Gili S, Grosso Marra W, D'Ascenzo F, Lonni E, Calcagno A, Cannillo M, Ballocca F, Cerrato E, Pianelli M, Barbero U, Mancone M, DiNicolantonio JJ, Lavie CJ, Omedè P, Montefusco A, Bonora S, Gasparini M, Biondi-Zoccai G, Moretti C, and Gaita F
- Subjects
- Adult, Anticholesteremic Agents, Atorvastatin, Cholesterol, LDL, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Primary Prevention, Pyrroles, Rosuvastatin Calcium, Simvastatin, HIV Infections
- Abstract
The efficacy and safety of different statins for human immunodeficiency virus (HIV)-positive patients in the primary prevention setting remain to be established. In the present meta-analysis, 18 studies with 736 HIV-positive patients receiving combination antiretroviral therapy (cART) and treated with statins in the primary prevention setting were included (21.0% women, median age 44.1 years old). The primary endpoint was the effect of statin therapy on total cholesterol (TC) levels. Rosuvastatin 10 mg and atorvastatin 10 mg provided the largest reduction in TC levels [mean -1.67, 95% confidence interval (CI) (-1.99, -1.35) mmol/L; and mean -1.44, 95% CI (-1.85, -1.02) mmol/L, respectively]. Atorvastatin 80 mg and simvastatin 20 mg provided the largest reduction in low-density lipoprotein (LDL) [mean -2.10, 95% CI (-3.39, -0.81) mmol/L; and mean -1.57, 95% CI (-2.67, -0.47) mmol/L, respectively]. Pravastatin 10-20 mg [mean 0.24, 95% CI (0.10, 0.38) mmol/L] and atorvastatin 10 mg [mean 0.15, 95% CI (0.007, 0.23) mmol/L] had the largest increase in high-density lipoprotein, whereas atorvastatin 80 mg [mean -0.60, 95% CI (-1.09, -0.11) mmol/L] and simvastatin 20 mg [mean -0.61, 95% CI (-1.14, -0.08) mmol/L] had the largest reduction in triglycerides. The mean discontinuation rate was 0.12 per 100 person-years [95% CI (0.05, 0.20)], and was higher with atorvastatin 10 mg [26.5 per 100 person-years, 95% CI (-13.4, 64.7)]. Meta-regression revealed that nucleoside reverse transcriptase inhibitors-sparing regimens were associated with reduced efficacy for statin's ability to lower TC. Statin therapy significantly lowers plasma TC and LDL levels in HIV-positive patients and is associated with low rates of adverse events. Statins are effective and safe when dose-adjusted for drug-drug interactions with cART., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)
- Published
- 2016
- Full Text
- View/download PDF
245. HCV NS3 naturally occurring variants in HIV/HCV coinfected DAA-naïve patients: consideration for HCV genotyping resistance testing.
- Author
-
Ruggiero T, Burdino E, Calcagno A, Bonora S, Boglione L, Di Perri G, and Ghisetti V
- Subjects
- Antiviral Agents, Cohort Studies, Coinfection, Female, Genotype, Humans, Male, Middle Aged, HIV Infections complications, Hepacivirus genetics, Hepatitis C complications, Hepatitis C virology, Viral Nonstructural Proteins genetics
- Abstract
Purpose: Data on the frequency of HCV naturally occurring drug-resistant variants (RAVs) at baseline in HIV/HCV coinfected patients are scarce., Methods: NS3-HCV RAVs were studied by full-population direct sequencing from plasma specimens of 345 DAA-naïve patients with HCV chronic hepatitis (159 of them with HIV/HCV-coinfection)., Results: NS3 RAVs were identified in 31.5 % of patients, with a significant proportion of HIV/HCV coinfected DAA-naïve patients compared to those with HCV monoinfection (38 vs. 25 % p = 0.0104, OR 1.84; 95 % CI 1.162-2.916)., Conclusions: HCV resistance genotyping test before treatment may be worth in special populations such as HIV/HCV coinfection to optimize patient treatment.
- Published
- 2016
- Full Text
- View/download PDF
246. Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines.
- Author
-
Calcagno A, Cusato J, Marinaro L, Trentini L, Alcantarini C, Mussa M, Simiele M, D'Avolio A, Di Perri G, and Bonora S
- Subjects
- Adult, Anti-HIV Agents blood, Anti-HIV Agents urine, Creatinine blood, Creatinine urine, Cross-Sectional Studies, Drug Interactions, Drug Therapy, Combination, Female, Heterozygote, Homozygote, Humans, Kidney drug effects, Kidney metabolism, Kidney physiopathology, Linear Models, Male, Membrane Transport Proteins metabolism, Middle Aged, Multidrug Resistance-Associated Proteins metabolism, Multivariate Analysis, Phenotype, Protease Inhibitors pharmacokinetics, Renal Elimination, Reverse Transcriptase Inhibitors adverse effects, Reverse Transcriptase Inhibitors blood, Reverse Transcriptase Inhibitors urine, Risk Assessment, Risk Factors, Tenofovir adverse effects, Tenofovir blood, Tenofovir urine, Anti-HIV Agents pharmacokinetics, Membrane Transport Proteins genetics, Multidrug Resistance-Associated Proteins genetics, Pharmacogenetics methods, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Reverse Transcriptase Inhibitors pharmacokinetics, Tenofovir pharmacokinetics
- Abstract
The HIV virus and hepatitis B virus nucleotide reverse transcriptase inhibitor tenofovir has been associated with proximal tubular toxicity; the latter was found to be predicted by plasma concentrations and with single-nucleotide polymorphisms in transporters-encoding genes. A cross-sectional analysis in adult HIV-positive patients with estimated creatinine clearance >60 ml min
-1 was performed. Twelve-hour plasma and urinary tenofovir concentrations and single-nucleotide polymorphisms in several transporter-encoding genes were analysed. In 289 patients 12-h tenofovir plasma, urinary and urinary to plasma ratios were 69 ng ml-1 (interquartile range 51.5-95), 24.3 mg ml-1 (14.3-37.7) and 384 (209-560). At multivariate analysis estimated creatinine clearance, protease inhibitors co-administration and SLC28A2 CT/TT genotypes were independently associated with plasma tenofovir exposure; ABCC10 GA/AA genotypes and protease inhibitor co-administration were independently associated with the urinary to plasma tenofovir ratio. Tenofovir clearance was associated with genetic polymorphisms in host genes and with co-administered drugs: if confirmed by ongoing studies these data may inform treatment tailoring and/or dose reductions.- Published
- 2016
- Full Text
- View/download PDF
247. Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the Co-Administration of Other Drug Classes in Routine Clinical Practice.
- Author
-
Costarelli S, Cozzi-Lepri A, Lapadula G, Bonora S, Madeddu G, Maggiolo F, Antinori A, Galli M, Di Perri G, Viale P, d'Arminio Monforte A, and Gori A
- Subjects
- Adult, Drug Therapy, Combination methods, Female, Humans, Male, Middle Aged, Ritonavir administration & dosage, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, HIV Protease Inhibitors administration & dosage, Reverse Transcriptase Inhibitors administration & dosage, Tenofovir administration & dosage
- Abstract
Background: In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF., Methods: All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment)., Results: 3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4-8.5) by 2 years and 14.1% (95%CI:12.2-16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF., Conclusion: In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome., Competing Interests: The authors of this manuscript have the following competing interests: SC received speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie and ViivHealthcare, travel grants from Gilead, ViivHealthcare and Bristol-Meyers and has been an employee of Gilead Sciences between 2012 and 2013; ACL received no grants; GL received speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie and Novartis and travel grants from Gilead, Merck, Abbvie, Boerhinger and Bristol-Meyers; SB received board membership grants and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare; GM received board membership grants and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare and travel meeting expenses from Janssen, Gliead Sciences and ViivHealthcare; FM received board membership grants from Gliead Sciences, Bristol-Meyers Squibb, Merck and ViivHealthcare and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb and ViivHealthcare; AA received consultancy and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare and travel meeting expenses from Abbvie and ViivHealthcare; MG received board membership grants consultancy and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare, travel meeting expenses from Abbvie and ViivHealthcare; GD received board membership grants and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare and speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare; PV received no grants; ADM received speaker grants from Janssen, Gliead Sciences, Bristol-Meyers Squibb, Abbvie and Merck; AG received board membership grants and speaker grants from Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare and speaker grants from Gliead Sciences, Bristol-Meyers Squibb, Abbvie, Merck and ViivHealthcare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2016
- Full Text
- View/download PDF
248. [Treating HIV disease: back to the patient?]
- Author
-
Girardi E, d'Arminio Monforte A, Camoni L, Pezzotti P, Guaraldi G, Ammassari A, Antinori A, Bonora S, Mussini C, Cingolani A, Corbelli GM, Adami S, Degli Esposti L, and Andretta M
- Subjects
- Anti-HIV Agents, Chronic Disease, Comorbidity, Humans, Prevalence, HIV Infections
- Abstract
HIV disease has dramatically changed in the last two decades from a progressive, lethal disease to a chronic manageable condition. These changes are due to the availability of potent antiretroviral combination therapy, which also have the potential to contribute significantly to the control of the epidemic. Among persons living with HIV, incidence of immunosuppression-related opportunistic illnesses has clearly decreased, while an increase was observed in the prevalence of age-related noncommunicable comorbidities, including cardiovascular, metabolic, renal, bone and hepatic disease, due to chronic inflammatory state and to an overall aging of the population of persons with HIV. It has been predicted that by 2030 more than 80% of older persons with HIV will have at least one comorbidity, compared to 19% of non HIV-infected persons, and that one fourth of these persons will have three or more comorbidities. Among persons with HIV, the prevalence of frailty is increasing. Choice of therapeutic approach to HIV disease should take into account, in addition to the ability of drug combination to suppress viral replication, the potential for long term adherence to treatment, the lack of long term toxicity, the possibility to fully restore immune function and prevent immune activation, thus reducing the risk of chronic inflammation related disease. In addition the overall impact of treatment on patients' well-being must be considered, and patients related outcomes should be used to measure this impact.
- Published
- 2016
- Full Text
- View/download PDF
249. Coherence-Gated Sensorless Adaptive Optics Multiphoton Retinal Imaging.
- Author
-
Cua M, Wahl DJ, Zhao Y, Lee S, Bonora S, Zawadzki RJ, Jian Y, and Sarunic MV
- Subjects
- Algorithms, Animals, Mice, Microscopy, Fluorescence, Multiphoton methods, Microscopy, Interference instrumentation, Microscopy, Interference methods, Refractometry instrumentation, Refractometry methods, Reproducibility of Results, Lenses, Microscopy, Fluorescence, Multiphoton instrumentation, Optics and Photonics instrumentation, Retina metabolism
- Abstract
Multiphoton microscopy enables imaging deep into scattering tissues. The efficient generation of non-linear optical effects is related to both the pulse duration (typically on the order of femtoseconds) and the size of the focused spot. Aberrations introduced by refractive index inhomogeneity in the sample distort the wavefront and enlarge the focal spot, which reduces the multiphoton signal. Traditional approaches to adaptive optics wavefront correction are not effective in thick or multi-layered scattering media. In this report, we present sensorless adaptive optics (SAO) using low-coherence interferometric detection of the excitation light for depth-resolved aberration correction of two-photon excited fluorescence (TPEF) in biological tissue. We demonstrate coherence-gated SAO TPEF using a transmissive multi-actuator adaptive lens for in vivo imaging in a mouse retina. This configuration has significant potential for reducing the laser power required for adaptive optics multiphoton imaging, and for facilitating integration with existing systems.
- Published
- 2016
- Full Text
- View/download PDF
250. Zika virus infection in two travelers returning from an epidemic area to Italy, 2016: Algorithm for diagnosis and recommendations.
- Author
-
Calleri G, Burdino E, Bonora S, Raso R, Ghisetti V, and Caramello P
- Subjects
- Adult, Female, Humans, Italy, Male, Real-Time Polymerase Chain Reaction, Venezuela epidemiology, Zika Virus genetics, Zika Virus isolation & purification, Zika Virus Infection epidemiology, Zika Virus Infection virology, Algorithms, Epidemics, Travel, Zika Virus Infection diagnosis
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.