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1.
Antibiotics (Basel) ; 13(5)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38786116

RESUMO

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.

2.
Environ Sci Pollut Res Int ; 31(15): 22830-22846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38409386

RESUMO

A machine learning-based approach is applied to simulate and forecast forest fires in the Golestan province in Iran. A dataset for no-fire, medium confidence (MC) fire events, and high confidence (HC) fire events is constructed from MODIS-MOD14A2. Nine climate variables from NASA's FLDAS are used as input variables, and 12 dates and 915 study points are considered. Three machine learning ensemble multi-label classifiers, gradient boosting (GBC), random forest (RFC), and extremely randomized tree (ETC), are used for forest fire simulation for the period 2000 to 2021, and ETC is found to be the most accurate classifier. Future fire projection for the near-future period of 2030 to 2050 is carried out with the ETC model, using CMIP6 EC-Earth3-SSP245 General Circulation Model (GCM) data. It is projected that MC forest fire occurrences will decrease, while HC forest fire occurrences will increase, and that the summer months, especially September, will be the most affected by fire.


Assuntos
Incêndios , Incêndios Florestais , Irã (Geográfico) , Clima , Estações do Ano
3.
Environ Sci Pollut Res Int ; 30(7): 18509-18521, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36217045

RESUMO

Sediment pick-up rate has been investigated using experimental and numerical approaches. However, the use of soft computing methods for its prediction has received less attention so far. In this study, genetic programming (GP), grammatical evolution (GE), and gradient boosting machine (GBM) algorithms are employed to develop a relation in dimensionless form for predicting sediment pick-up rate in open channel flow based on two experimental datasets. Dimensionless Froude number, particle diameter, and depth-averaged turbulent kinetic energy are input variables for prediction. Prediction performance is evaluated with performance indices (root mean square error, mean absolute error, and coefficient of correlation), visual comparisons (scatter, dot, and Bland-Altman plots), and uncertainty indicators (Tsallis and Renyi entropies). Three mathematical expressions for sediment pick-up rate prediction are obtained, with GE producing the most accurate results.


Assuntos
Algoritmos , Incerteza
4.
Water Sci Technol ; 85(1): 383-397, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35050890

RESUMO

Most previous quantitative research conducted on urban creep and urban expansion has focused on small areas, short time periods, case studies with fairly uniform housing stock and demographic makeup, and the characterisation of urban creep and expansion exclusively in terms of impervious area changes without quantification of the consequential hydrological impact, i.e., increase in surface runoff volume and peak flows in a catchment. This study, using satellite imagery, catchment characteristics data, geographic information system and hydrologic modelling, presents, for the first time, a long-term analysis of urban creep and expansion. The case study is the Ouseburn catchment in Newcastle upon Tyne, a wide-ranging catchment made up of rural, suburban and urban areas, over a period of seven decades. The rate of increase of impervious surfaces is found not to be constant in time; the significant impact of this variation on the catchment's hydrologic response is quantified. This has overall caused a substantial flow volume increase in the Ouseburn over the study period, e.g. 48% for a 1 in 5 years rainfall event. The conclusions obtained are likely representative of many large towns and cities across the United Kingdom and the methodology presented can be easily replicated in other study areas.


Assuntos
Chuva , Movimentos da Água , Cidades , Hidrologia
5.
Sci Rep ; 12(1): 1239, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075188

RESUMO

Travertine crystal growth ripples are used to reconstruct the early hydraulic history of the Anio Novus aqueduct of ancient Rome. These crystalline morphologies deposited within the aqueduct channel record the hydraulic history of gravity-driven turbulent flow at the time of Roman operation. The wavelength, amplitude, and steepness of these travertine crystal growth ripples indicate that large-scale sustained aqueduct flows scaled directly with the thickness of the aqueous viscous sublayer. Resulting critical shear Reynolds numbers are comparable with those reconstructed from heat/mass transfer crystalline ripples formed in other natural and engineered environments. This includes sediment transport in rivers, lakes, and oceans, chemical precipitation and dissolution in caves, and melting and freezing in ice. Where flow depth and perimeter could be reconstructed from the distribution and stratigraphy of the travertine within the Anio Novus aqueduct, flow velocity and rate have been quantified by deriving roughness-flow relationships that are independent of water temperature. More generally, under conditions of near-constant water temperature and kinematic viscosity within the Anio Novus aqueduct channel, the travertine crystal growth ripple wavelengths increased with decreasing flow velocity, indicating that systematic changes took place in flow rate during travertine deposition. This study establishes that travertine crystal growth ripples such as those preserved in the Anio Novus provide a sensitive record of past hydraulic conditions, which can be similarly reconstructed from travertine deposited in other ancient water conveyance and storage systems around the world.

6.
Environ Monit Assess ; 193(12): 798, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773156

RESUMO

Dissolved oxygen (DO) concentration in water is one of the key parameters for assessing river water quality. Artificial intelligence (AI) methods have previously proved to be accurate tools for DO concentration prediction. This study presents the implementation of a deep learning approach applied to a recurrent neural network (RNN) algorithm. The proposed deep recurrent neural network (DRNN) model is compared with support vector machine (SVM) and artificial neural network (ANN) models, formerly shown to be robust AI algorithms. The Fanno Creek in Oregon (USA) is selected as a case study and daily values of water temperature, specific conductance, streamflow discharge, pH, and DO concentration are used as input variables to predict DO concentration for three different lead times ("t + 1," "t + 3," and "t + 7"). Based on Pearson's correlation coefficient, several input variable combinations are formed and used for prediction. The model prediction performance is evaluated using various indices such as correlation coefficient, Nash-Sutcliffe efficiency, root mean square error, and mean absolute error. The results identify the DRNN model ([Formula: see text]) as the most accurate among the three models considered, highlighting the potential of deep learning approaches for water quality parameter prediction.


Assuntos
Inteligência Artificial , Rios , Monitoramento Ambiental , Redes Neurais de Computação , Oxigênio/análise
7.
Nanomaterials (Basel) ; 11(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069534

RESUMO

In the present work, an Ir/CeO2 catalyst was prepared by the deposition-precipitation method and tested in the decomposition of hydrazine hydrate to hydrogen, which is very important in the development of hydrogen storage materials for fuel cells. The catalyst was characterised using different techniques, i.e., X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) equipped with X-ray detector (EDX) and inductively coupled plasma-mass spectroscopy (ICP-MS). The effect of reaction conditions on the activity and selectivity of the material was evaluated in this study, modifying parameters such as temperature, the mass of the catalyst, stirring speed and concentration of base in order to find the optimal conditions of reaction, which allow performing the test in a kinetically limited regime.

8.
Diagnostics (Basel) ; 12(1)2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-35054179

RESUMO

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

9.
Nanomaterials (Basel) ; 10(3)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168904

RESUMO

The effect of support, stabilizing agent, and Pd nanoparticles (NPs) size was studied for sodium muconate and t,t-muconic acid hydrogenation to bio-adipic acid. Three different activated carbons (AC) were used (Norit, KB, and G60) and carbon morphology did not affect the substrate conversion, but it greatly influenced the adipic acid yield. 1% Pd/KB Darco catalyst, which has the highest surface area and Pd surface exposure, and the smallest NPs size displayed the highest activity. Furthermore, the effect of the amount of the protective agent was studied varying metal/protective agent weight ratios in the range of 1/0.00-1/1.20, using KB as the chosen support. For sodium muconate reduction 1% Pd/KB_1.2 catalyst gave the best results in terms of activity (0.73 s-1), conversion, and adipic acid yield (94.8%), while for t,t-muconic acid hydrogenation the best activity result (0.85 s-1) was obtained with 1% Pd/KB_0.0 catalyst. Correlating the results obtained from XPS and TEM analyses with catalytic results, we found that the amount of PVA (polyvinyl alcohol) influences mean Pd NPs size, Pd(0)/Pd(II) ratio, and Pd surface exposure. Pd(0)/Pd(II) ratio and Pd NPs size affected adipic acid yield and activity during sodium muconate hydrogenation, respectively, while adipic acid yield was related by exposed Pd amount during t,t-muconic acid hydrogenation. The synthesized catalysts showed higher activity than commercial 5% Pd/AC.

10.
Phys Chem Chem Phys ; 22(7): 3883-3896, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32040127

RESUMO

Hydrogen transport and storage technology remain one of the critical challenges of the hydrogen economy. Hydrazine (N2H4) is a carbon-free hydrogen carrier which has been widely used as fuel in the field of space exploration. We have combined experiments and computer simulations in order to gain a better understanding of the N2H4 decomposition on Ir catalyst, the most efficient catalyst for hydrazine decomposition up to date. We have identified metallic Ir rather than IrO2 as the active phase for hydrazine decomposition and carried out density functional theory (DFT) calculations to systematically investigate the changes in the electronic structure along with the catalytic decomposition mechanisms. Three catalytic mechanisms to hydrazine decomposition over Ir(111) have been found: (i) intramolecular reaction between hydrazine molecules, (ii) intramolecular reaction between co-adsorbed amino groups, and (iii) hydrazine dehydrogenation assisted by co-adsorbed amino groups. These mechanisms follow five different pathways for which transition states and intermediates have been identified. The results show that hydrazine decomposition on Ir(111) starts preferentially with an initial N-N bond scission followed by hydrazine dehydrogenation assisted by the amino group produced, eventually leading to ammonia and nitrogen production. The preference for N-N scission mechanisms was rationalized by analyzing the electronic structure. This analysis showed that upon hydrazine adsorption, the π bond between nitrogen atoms becomes weaker.

12.
Nanomaterials (Basel) ; 9(2)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791618

RESUMO

This paper studies the cooperative effect of Au nanoparticles deposited on vanadyl pyrophosphate oxide (VPO) in the liquid phase oxidation of benzyl alcohol. VPO was prepared using the classical method by thermally treating VOHPO4·0.5H2O precursor in reacting atmosphere at 420 °C for a period of 72 h. Au nanoparticles were deposited by incipient wetness method. The catalysts were characterized by means of XRD, TEM, XPS and Raman. The bulk VPO catalyst contains vanadyl pyrophosphate phase ((VO)2P2O7), and a small amount of VOPO4. The catalytic system exhibits a high activity in the base-free liquid phase oxidation of alcohols compared to Au on activated carbon, classic catalyst used for this type of reaction. Au/VPO showed a high peculiar selectivity to benzyl benzoate (76%), an important product used in the pharmaceutical and perfume industries. This behavior might be ascribed to the presence of strong acid sites of VPO, as determined by liquid phase titration. Stability tests performed on Au/VPO showed a deactivation of 10% after the first run, but a constant conversion along the following five cycles. This phenomenon can be attributed to the increase of mean Au particle size (from 19.1 to 23.4 nm) after recycling tests as well as the partial leaching of Au and V in the reaction media. Moreover, XRD evidenced a modification in the VPO structure with the partial formation of VOHPO4·0.5H2O phase.

13.
Top Catal ; 61(3): 254-266, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30956509

RESUMO

Safe and efficient hydrogen generation and storage has received much attention in recent years. Herein, a commercial 5 wt% Pd/C catalyst has been investigated for the catalytic, additive-free decomposition of formic acid at mild conditions, and the experimental parameters affecting the process systematically have been investigated and optimised. The 5 wt% Pd/C catalyst exhibited a remarkable 99.9% H2 selectivity and a high catalytic activity (TOF = 1136 h-1) at 30 °C toward the selective dehydrogenation of formic acid to H2 and CO2. The present commercial catalyst demonstrates to be a promising candidate for the efficient in-situ hydrogen generation at mild conditions possibiliting practical applications of formic acid systems on fuel cells. Finally DFT studies have been carried out to provide insights into the reactivity and decomposition of formic acid along with the two-reaction pathways on the Pd (111) surface.

14.
Int J Mol Sci ; 17(4): 434, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-27023519

RESUMO

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.


Assuntos
Infecções por HIV/diagnóstico , Transtornos Neurocognitivos/etiologia , Adulto , Alcoolismo/complicações , Estudos de Coortes , Coinfecção/complicações , Coinfecção/diagnóstico , Feminino , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite B/diagnóstico , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/epidemiologia , Testes Neuropsicológicos , Prevalência , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicações
15.
HIV Clin Trials ; 16(4): 157-62, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-26057863

RESUMO

OBJECTIVE: A therapeutic vaccination based on a synthetic peptide (AT20) representative of the HIV-1 matrix protein p17 (p17) functional region, coupled to keyhole limpet hemocyanin (KLH) AT20-KLH was capable of inducing the production of high-avidity antibodies (Abs) toward a previous untargeted p17 hotspot of functional activity in highly active antiretroviral therapy (HAART)-treated HIV-1-infected patients. Since avidity of Abs after immunization and the retention of antigens are important in sustaining the long-lasting production of specific humoral responses, we asked whether AT20-KLH vaccination would result in development of a long-lived immune response. METHODS: The long-term duration of Ab response to AT20-KLH has been evaluated in 10 patients previously enrolled for the AT20-KLH vaccination trial at day 898 post-immunization. Ab titer and their avidity was assessed using specifically designed ELISA assays, whereas their neutralizing capacity was estimated in vitro using a 'wound sealing assay'. RESULTS: Data obtained show that high titers of specific anti-AT20 Abs were maintained at more than 2 years after the last immunization. Furthermore, these Abs were capable to neutralize exogenous p17, as assessed by ability of sera derived from AT20-KLH-immunized patients to block the ability of p17 to promote cell migration in vitro. CONCLUSION: This finding attests for a successful AT20-KLH vaccine molecule formulation and for an effective HAART-dependent Ab persistence.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Hemocianinas/imunologia , Imunidade Humoral , Peptídeos/imunologia , Adjuvantes Imunológicos , Adulto , Terapia Antirretroviral de Alta Atividade , Epitopos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
17.
Mediterr J Hematol Infect Dis ; 5(1): e2013071, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24363886

RESUMO

SETTING: Culture-positive tuberculosis (TB) diagnosed in the metropolitan area of Milan (Italy) over a 5-year period (1995-1999). OBJECTIVE: To assess the impact of short-course hospitalization upon diagnosis on the overall risk of TB clustering. DESIGN: Restriction fragment length polymorphism profiles with a similarity of 100% defined a cluster. Uni- and multivariable logistic regression models were performed to assess factors associated with clustering. RESULTS: Among 1139 patients, 392 (34.4%) were hospitalized before or soon after diagnosis, 405 (35.6%) received domiciliary treatment since the diagnosis and 392 (30%) had no information about initial clinical management. One hundred fifteen molecular clusters involving 363 patients were identified. Using multivariable analysis, hospitalization was not significantly associated with clustering (OR 1.06, 95%CI 0.75-1.50, p=0.575). Subjects aged >65 years old (OR 0.60; 95CI%:0.37-0.95; p=0.016) and non-Italian born patients (OR 0.56; 95%CI:0.41-0.76; p<0.001) were running a lower risk of clustering. Conversely, HIV co-infected patients (OR 1.88, 95%CI:1.20-2.95, p=0.006) and those with MDR TB (OR 2.50, 95%CI:1.46-4.25, p=0.001) were significantly more likely to be involved in clusters. CONCLUSION: In our cohort, domiciliary treatment was not associated with TB clustering. Expanding domiciliary treatment upon diagnosis appears as an advisable measure to reduce unnecessary costs for the health care system.

18.
HIV Clin Trials ; 13(5): 245-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23134625

RESUMO

BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data after standard HAART regimens are limited. METHODS: This was a substudy of a trial in 91 antiretroviral-naïve patients randomized to tenofovir + emtricitabine + atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups at week 48 were calculated. Indications for lipid-lowering interventions and low HDL-C were also studied. RESULTS: ANCOVA showed that, with respect to patients receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and 2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not differ significantly. CONCLUSIONS: Patients prescribed EFV had greater increases in TC, LDL-C, and HDL-C. Although no significant differences were detected between the 2 groups for the TC:HDL ratio and for indications to start lipid-lowering interventions, large HDLp increased more in the EFV group compared to the ATV/r group, suggesting a protective effect associated with EFV use.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , HDL-Colesterol/sangue , Hipercolesterolemia/induzido quimicamente , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Sulfato de Atazanavir , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Ciclopropanos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
19.
Drugs ; 72(9): 1161-73, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22646049

RESUMO

Atazanavir (Reyataz®) is a protease inhibitor (PI) for the treatment of HIV infection. Several trials have demonstrated the good efficacy and toxicity profile of atazanavir boosted by ritonavir (atazanavir/r). However, several toxicity events and pharmacokinetic issues due to drug-to-drug interactions (partly related to ritonavir) may complicate atazanavir/r therapy. This is why regimens with unboosted atazanavir have been experimented with and are used in clinical practice. The aim of this article is to identify the clinical settings in which unboosted atazanavir may be a safe and effective option for the long-term control of HIV replication. Despite the fact that a favourable lipid profile and good gastrointestinal tolerability have been reported in comparative trials, unboosted atazanavir should not be considered an optimal choice for treatment-naive patients. In fact, boosting with ritonavir produces higher atazanavir plasma levels, which are beneficial in terms of efficacy, especially in untreated patients with high plasma HIV RNA. Clinical data indicate that, in patients with sustained undetectable HIV RNA and without previous virological failure or HIV drug resistance-associated mutations, a switch to unboosted atazanavir-based regimens is a feasible option to control and prevent toxicity events, especially in patients who cannot tolerate ritonavir and in those with severe hyperbilirubinaemia on atazanavir/r. Moreover, while unboosted atazanavir must not be used in pregnant women, it is a recommended option in special populations, such as patients with moderate liver insufficiency. Lastly, unboosted atazanavir in combination with raltegravir may allow the construction of a well tolerated and effective regimen without nucleoside reverse transcriptase inhibitors in patients for whom these drugs are contraindicated. In conclusion, there is a good rationale, significant clinical interest and accumulating clinical experience with unboosted atazanavir-based regimens, although this formulation should be used only in specific situations and as a maintenance strategy. Moreover, therapeutic drug monitoring could be useful in specific circumstances (such as in patients with liver impairment or in case of potential drug-drug interactions).


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Sulfato de Atazanavir , Interações Medicamentosas , Quimioterapia Combinada , Feminino , HIV/efeitos dos fármacos , Inibidores da Protease de HIV/efeitos adversos , Humanos , Masculino , Oligopeptídeos/efeitos adversos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Gravidez , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
20.
AIDS Res Ther ; 9(1): 18, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22703595

RESUMO

BACKGROUND: The aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART. METHODS: We performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4-8 months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ≥100/mm3 from baseline to month 4-8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome. RESULTS: The early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p = 0.01) or NNRTI (88.5% versus 84.7%; p = 0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ≥100/mm3 CD4+ increase within 8 months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p = 0.003) and NNRTI (63.7% versus 74.7%; p < 0.001). Regarding late CD4+ increase, positive HCV Ab appeared to impair immune reconstitution in terms of absolute CD4+ T-cell count increase both in patients treated with PI/r (p = 0.013) and in those treated with NNRTI (p = 0.002). This was confirmed at a multivariable analysis up to 12 months of follow-up. CONCLUSIONS: In this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12 months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.

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