bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV‐infected patients show functionally defective high‐density lipoprotein (HDL) paralleled with changes in HDL‐associated proteins
Authors: Estrada V , Gómez‐Garre M , Ortega‐Hernandez A , Muñoz‐Pacheco P , Serrano‐Vilar S , Sainz‐Costa T , Carranza M , Rodrigo M , Fernández‐Cruz A 
Published: November 2012

Purpose of the studyEpidemiological studies have consistently demonstrated an inverse association between plasma HDL concentrations and cardiovascular risk. Although this cardioprotective role has been mainly attributed to its role in promoting cellular cholesterol efflux, there is an emerging interest in the anti‐inflammatory and antioxidant properties of HDL. The aim of the study is to investigate the anti‐inflammatory properties of HDL isolated from HIV‐infected patients.MethodsCross‐sectional study of 113 HIV‐infected patients and 70 non‐infected control subjects without evident CVD. From each subject, HDL was isolated by ultracentrifugation and its anti‐inflammatory status was tested as its ability to inhibit MCP‐1‐induced migration of the monocytic cell line THP‐1 using transwell cell culture chamber inserts with micropore filters of 5 microns pore size. HDL‐associated proteins were measured by commercial ELISAs.ResultsTwenty‐three HIV‐infected patients were ART‐naïve (32±15 years, 66.7% male) and ninety were currently on ART (46±11 years, 78.9 % male). Most patients on ART (91.1%) had undetectable viral load (<50 copies/mL). When compared to healthy subjects, both naïve and treated HIV‐infected patients had lower plasma HDL‐cholesterol levels (naïve: 45±12, ART: 50±10, controls: 55±10 mg/dL, p<0.05). HDL isolated from HIV naïve patients showed a significantly reduced anti‐inflammatory activity (THP‐1 monocyte migration capacity was 203% times higher in HIV patients than in control subjects). The anti‐inflammatory activity of HDL from ART‐treated HIV‐infected patients was significantly improved when compared to naïve patients, although it remained significantly lower than controls (130% THP‐1 monocyte migration vs controls). HDL from HIV‐infected patients had a decreased concentration of the anti‐inflammatory proteins Apo A1 (controls: 2.1±0.3, naïve: 1.4±0.2, ART: 1.6±0.1 mg/ml) and LCAT (controls: 0.53±0.09, naïve: 0.34±0.06, ART: 0.48±0.05 μg/ml), and increased of the pro‐inflammatory protein serum amiloid (controls: 1.42±0.53, naïve: 3.23±1.29, ART: 2.72±0.70 μg/ml) than healthy controls.ConclusionsOur data demonstrate HIV‐infected patients, even with effective therapy, showed a marked reduction of HDL anti‐inflammatory properties. This dysfunctional HDL seems to be associated with changes HDL composition and may contribute to the increased CVD risk observed in HIV infection.
Effects of switching to PI monotherapy on measures of lipoatrophy: meta‐analysis of six randomized HIV clinical trials
Authors: Arribas J , Bernardino J , Hill A , Sawyer W , van Delft Y , Moecklinghoff C 
Published: November 2012

BackgroundSwitching from triple combination treatment to protease inhibitor (PI) monotherapy may prevent or reverse adverse events related to long‐term nucleoside analogues. Lipoatrophy is associated with long‐term use of thymidine analogues (zidovudine and stavudine).MethodsA detailed MEDLINE search was conducted to identify randomised clinical trials of triple combination treatment versus PI monotherapy. Summary results from analysis of changes in body composition (DEXA analysis) were collected: the mean change in limb fat and trunk fat to Week 48 or 96, and the percentage of patients with lipoatrophy (20% reduction from baseline in limb fat) or lipohypertrophy (20% rise from baseline in trunk fat).ResultsSix randomised trials of PI monotherapy versus triple therapy with data on body composition changes, measured by DEXA scanning at baseline and Week 48 or 96, were identified: Abbott‐613 (LPV/r vs ZDV/3TC/EFV, induction‐maintenance trial, n=105), Monark (LPV/r vs ZDV/3TC/LPV/r, first‐line trial, n=63), Kalesolo (LPV/r vs LPV/r +2NRTIs, switch trial, n=42), MONOI (DRV/r vs DRV/r + 2NRTIs, switch trial, n=156), MONARCH (DRV/r vs DRV/r + 2NRTIs, switch trial, n=30) and KRETA (LPV/r vs LPV/r + ABC/3TC, switch trial, n=74). In the meta‐analysis, there were greater rises in limb fat in the PI monotherapy arms than the triple therapy arms (mean difference =277g, 95% CI=+36 to+517g, p=0.024). The percentage of patients with lipoatrophy was significantly lower in the PI monotherapy arms (4%) than the triple therapy arms (20%), (p=0.0005). There was no difference between PI monotherapy and triple therapy for mean change in trunk fat (mean difference=−73g, 95% CI = −621 to +475g, p=ns). There was also no significant difference in the risk of lipohypertrophy between the PI monotherapy arms (32%) and the triple therapy arms (27%) (p=ns). In each of the four analyses, there was no evidence for heterogeneity of treatment effects between the trials (Cochran's Q tests, p=ns for each comparison).ConclusionsIn this meta‐analysis, the risk of lipoatrophy was significantly lower for patients taking PI monotherapy, compared to triple therapy. There was no significant difference between the arms for lipohypertrophy. However, several of the trials included zidovudine in the control arm, which carries a higher risk of lipoatrophy than tenofovir and abacavir, which are now more widely used.
Longitudinal comparison of inflammatory, coagulation and metabolic biomarkers in patients who start ART versus patients who remain ART‐naïve
Authors: Bernardino J , Merino J , Serrano L , Estébanez M , Montes M , Zamora F , Pérez‐Valero I , González‐García J , Arribas J 
Published: November 2012

There are very limited data on the impact of ART initiation on inflammatory and coagulation biomarkers compared to patients who remain ART naïve [1]. We designed a prospective comparative study to evaluate these changes. Prospective observational cohort study of HIV‐infected patients who start ART and a group of age‐matched controls who remain ART‐naïve. Blood levels of insulin, fibrinogen, D‐dimer, high‐sensitivity PCR, inflammatory (IL‐1β, IL‐6, MCP‐1 and sCD40) and anti‐inflammatory cytokines (IL‐4), were compared at baseline, 24 weeks and 48 weeks. Summary of results: 94 patients included (57 treated, 37 controls). Baseline characteristics were balanced except for (treated/controls): median [IQR], HIV duration (0.9 [0.4–2.4] / 2.7 [0.6–5.5]) years, CD4 nadir (262 [198–317] / 452 [367–553]) cells/µl, viral load (4.4 [4–5.1] / 3.8 [3.1–4.4]) log cop/ml, current CD4 count (283 [213–323] / 525 [449–669]) cells/µl, HDL cholesterol (38 [29–45] / 41 [36–50]) mg/dl and female gender (8.8%/35%). There were no differences between groups in baseline biomarkers levels except that those starting ART had lower median [IQR] IL‐1β (4.1 [3.5–4.7] vs. 4.6 [3.7–6.8] pg/ml; p= 0.019) and lower IL–6 levels (4 [3.4–4.6] vs. 5.2 [4.2–6.6] pg/ml; p< 0.001). No significant correlation was found between biomarkers and baseline viral load. 91% of treated patients achieved viral suppression (<50 c/ml). There were statistically significant differences between groups at week 48 with lower (mean [95% CI]) D‐dimer (−138.2 [−268.0, −8.4] mg/L; p=0.001), IL‐1β (−0.6 [−0.9, −0.4] pg/ml; p<0.001) and higher IL‐4 (0.6 [0.2, 0.9] pg/ml; p=0.004) in those starting ART. In the ART‐naïve group there were significant increases of IL‐1β (1.3 [0.9, 1.6] pg/ml; p<0.001), sCD40 (22.7 [0.8, 44.6] AU; p=0.043), IL‐6 (0.5 [0.0, 0.9] pg/ml; p= 0.049) and a significant decrease of IL‐4 (−0.7 [−1.1, −0.3] pg/ml; p=0.001) levels. After 48 weeks of ART there were statistically significant decreases in pro‐inflammatory and coagulation markers (Figure 1) while levels of anti‐inflammatory cytokines (e.g. IL‐4) were significantly increased. Opposite trends were found in controls.In conclusion, compared to untreated controls, 48 weeks of effective ART significantly reduces pro‐inflammatory (IL‐1β, IL‐6), coagulation (fibrinogen, D‐dimer), and metabolic (insulin) markers and increases levels of an anti‐inflammatory cytokines like IL‐4.Median percentage changes in bio markers from baseline to week 48.image
Combined use of waist and thigh circumference to identify high‐risk, abdominally obese HIV+ patients
Authors: O'Neil T , Ross R , Zona S , Orlando G , Carli F , Garlassi E , Stentarelli C , Mussini C , Guaraldi G 
Published: November 2012

BackgroundWe examined whether the combination of waist (WC) and thigh (ThC) circumference improves the prediction of visceral adipose tissue (VAT) over WC and ThC independently in HIV‐infected men and women after correction for age. We also examined the independent associations between VAT, and the combination of WC and ThC with metabolic risk factors, metabolic syndrome, type 2 diabetes mellitus (T2DM) and prior cardiovascular events in HIV‐infected individuals.MethodsConsecutive patients attending the metabolic clinic of the University of Modena in Italy between 2005 and 2009 were recruited in this cross‐sectional study. Total and regional fat mass and lean mass were quantified using DEXA. A single CT image was taken for quantification of VAT and CAC. Prior cardiovascular events which occurred within a 5‐year period of the clinical evaluation were analysed. A cross‐fold test was used to explore different models in the ability to predict VAT in order to build an algorithm for VAT estimation (e‐VAT). Regression analysis were performed to determine the univariate and multivariate relations between WC, ThC, and age with VAT. A comparison of beta coefficients for VAT and e‐VAT to predict cardio‐metabolic risk and events were performed using multivariable regression models after correction for BMI and age.Results2322 HIV‐infected patients were recruited: median duration of HIV infection was 182 months (IQR 126–236); median nadir and current CD4 were 172 (IQR 68–262) and 515.5 (IQR 369–700) and 75% of them had undetectable HIV1‐VL. In this abstract only the results of men will be presented. Men (n=1481) had a mean age of 45.9±7.3 years, a BMI of 24.1 ± 3.8 kg/m2, a WC of 88.0±10.1 cm and a ThC of 47.8±4.3 cm. e‐VAT algorithm for men was: (5.44*WC)−(1.35*ThC)−(1.70*age)−348.1 In men, at multivariable regression models after correction for BMI and age, e‐VAT was concordant to VAT in predicting HOMA, MetS Risk, prior cardiovascular events (OR=1.01), was better than VAT in predicting T2DM (OR=1.00) and CAC>10 (OR=1.01) but was worse than VAT in predicting TC/HDL and TG.DiscussionWe confirm that ThC is inversely associated to VAT after correction for WC. e‐VAT is a sensitive tool to predict VAT more accurately than WC and ThC independently. e‐VAT proved to predict cardio‐metabolic risks and events in men and women, qualifying this variable for a potential clinical use.
The effect of zinc sulphate supplementation on atazanavir/ritonavir‐associated hyperbilirubinemia
Authors: Jackson A , Else L , Back D , Yapa M , Seymour N , Ringner‐Nackter L , Gazzard B , Boffito M , Moyle G 
Published: November 2012

BackgroundAtazanavir (ATV) causes an exposure dependent elevation of unconjugated hyperbilirubinemia (HBR) as a result of UGT1A1 inhibition. Zinc sulphate reduces unconjugated hyperbilirubinemia in individuals with Gilbert's syndrome. We assessed the changes in total and conjugated bilirubin following single dose and 14 daily doses of zinc sulphate (ZnSO4) and its impact on ATV pharmacokinetics (PK).MethodsHIV‐infected individuals stable on ATV/ritonavir (r) containing regimens with a total bilirubin level > 25 mmol/L were administered 125 mg once daily of as solvazinc effervescent tablets for 14 days. ATV and bilirubin concentrations were measured pre‐ATV‐dose, 2, 4, 6, 8 and 24 hours post‐ATV‐dose before ZnSO4 intake initiation (phase 1), after a single dose of ZnSO4 (phase 2), and following 14 days of ZnSO4 intake (phase 3). Changes in bilirubin and ATV concentrations in the absence and presence of ZnSO4 were evaluated by geometric mean ratios (GMR) and 90% confidence intervals (CI, phase 1 as reference).ResultsAll 16 male patients completed the study maintaining virologic suppression throughout. ZnSO4 was well tolerated. We observed statistically significant declines in total bilirubin Cmax and AUC0–24 of −12 and −13% after single dose ZnSO4 and −19 and −20% after steady state, compared to reference phase; GM Cmax decreasing from 57 nmol/L before zinc intake to 50 and 46 nmol/L after ZnSO4 single dose and steady state, respectively. No significant changes in conjugated bilirubin were observed, indicating that the changes were secondary to declines in the unconjugated fraction (data pending). ATV GMR (90% CI) for Ctrough, Cmax and AUC were −16% (−33 to +6), −8% (−20 to +8) and −12% (−23 to +0.1) after single dose ZnSO4, but changed by −26% (−38 to −11) −18% (−30 to −3) and −22% (31 to −12) after multiple dose ZnSO4 compared to reference. All individuals with the exception of one (whose levels were low throughout the study) maintained ATV concentration above the suggested MEC of 150 ng/mL.ConclusionsThe intake of ZnSO4 led to a moderate decrease in total bilirubin maximum concentration and overall exposure. However, a decrease in ATV concentrations was also observed. ZnSO4 supplementation may represent a useful tool in the management of ATV‐related HBR.
Incidence and risk factors of chronic renal disease in a cohort of Greek HIV‐1‐infected adults
Authors: Sakka V , Bakoyannis G , Chini M , Gargalianos P , Sambatakou H , Antoniadou A , Chrysos G , Paparizos V , Daikos G , Katsarou O , Touloumi G , Lazanas M 
Published: November 2012

Chronic kidney disease (CKD) in HIV‐infected patients is associated with both HIV and non‐HIV‐related factors. Initial renal dysfunction is silent and detectable only by laboratory tests such as the glomerular filtration rate (GFR) estimated by the Cockcroft‐Gault equation. Our objective was to assess possible risk factors for CKD in a cohort of Greek HIV‐1‐infected adults.MethodsPatients in the AMACS (Athens Multicenter AIDS Cohort Study) cohort with at least two available creatinine values were enrolled in the study. Renal dysfunction was defined as eGFR below 90 mL/min/1.73 m2. The Kaplan‐Meier estimator and the Cox proportional hazards model were used to analyze the occurrence and predictors of renal dysfunction.ResultsA total of 1073 patients were enrolled in the study; 255 (23.76%) had baseline eGFR below 90 mL/min/1.73 m2 and were excluded. Characteristics of the study population: men 88.4%, MSM 62.6%, median baseline age, CD4+count and viral load were 32.6 years, 413 cells/µL and 3.77 log10 copies/mL, respectively. 240 (29.3%) patients experienced an eGFR decrease below 90 mL/min/1.73 m2 during follow‐up period. Older age, female gender, heterosexual mode of transmission, lower baseline eGFR (all p<0.001), lower baseline CD4+(p=0.001), stage C (p=0.023), administration of cART (p<0.001) or other nephrotoxic agent (p=0.035) were the major risk factors in univariable analysis. Multivariable analysis identified older age [hazard ratio (HR) 1.289 per 10 years, p<0.001] and female gender (HR vs male: 1.899, p<0.001), as the major factors associated with increased hazard of developing CRD, whereas baseline eGFR <110 (HR vs eGFR <110: 0.245, p<0.001) and current CD4+count ≥350 cells/µL (HR 0.564, p=0.003) were significant protective factors.ConclusionIn this large cohort of HIV‐infected Greek patients, almost one‐third (29.3%) experienced some degree of renal dysfunction during HIV infection. Older age and female gender were major predictors of CKD, whereas high current CD4+count and baseline eGFR were protective.
Renal dysfunction and factors associated among newly identified HIV‐infected patients in Brazzaville, Republic of Congo
Authors: Ekat E , Diafouka D 
Published: November 2012

With the introduction of nephrotoxic in recent WHO recommendation, it became necessary to determine prevalence and factors associated with renal dysfunction among patients newly identified HIV‐infected in Brazzaville.MethodsDescriptive and analytical study of patients newly diagnosed HIV‐infected at the Ambulatory Treatment Center in Brazzaville, Republic of Congo between January 1st, 2009 and December 31st, 2010. Estimated glomerular filtration rate (eGFR) was assessed using the Cockroft‐Gault formula (CGCl) and modification of diet in renal disease (MDRD) equation. Patients had renal dysfunction mild, moderate or severe when eGFR were respectively 60–89 ml/min, 30–59 ml/min and<30 ml/min with the GCCl and MDRD. To determine factors associated with renal failure (defined as GCCl<60 ml/min), univariate analysis followed by multivariate logistic regression analysis was performed.ResultsWe evaluated 562 patients newly identified HIV‐infected, median age was 38.84 (interquartile range (IQR): 33.18–46.24) years, all patients were of African origin, 61.1% were female, median BMI was 20.30 (IQR: 17.96–22.89) kg/m2, median CD4 count was 192 (IQR: 81–350) cells/mm3 and 70.8% were at WHO stage III/IV. GFR was lower using CGCl (median 74.99 ml/min, 26.1%<60 ml/min) versus MDRD (95.59 ml/min/1.73 m2, 7.9%<60 ml/min/1.73 m2). Two hundred and fifty‐seven patients (47.2%) using CGCl versus 138 (32.6%) with the MDRD had mild, 126 patients (23.1%) versus 33 (5.9%) respectively had moderate, and 16 patients (3%) versus 11 patients (2%) respectively had severe renal dysfunction. Factors associated with renal dysfunction in multivariate analysis included age superior to 40 years (adjusted odds ratio (aOR): 0.37 [95% CI: 0.22‐0.61]; p=0.0001), CD4+ T‐cell count below 200 cells/mm3 (aOR: 1.72 [95% CI: 1.04–2.83]; p=0.035) and BMI less than 18.5 kg/m2 (aOR: 4.39 [95% CI: 2.63–7.33]; p<0.0001).ConclusionsThis study shows a high prevalence of renal dysfunction in patients newly diagnosed HIV positive in Brazzaville. Necessity is now beside serum creatinine assay performed in the initial assessment as recommended by WHO, to also perform urine dipstick for better monitoring of these patients before initiating antiretroviral therapy.
HIV‐associated idiopathic non‐cirrhotic portal hypertension is an underdiagnosed disorder: results of a large cohort study
Authors: Koëter T , Rossing H , Schouten J , Taimr P , de Knegt R , Hansen B , Janssen H , van der Ende M 
Published: November 2012

Purpose of the studyIdiopathic non‐cirrhotic portal hypertension (INCPH) has been reported increasingly in patients with chronic HIV infection. However, several aspects of this disorder remain to be elucidated. The aim of our study was to evaluate the prevalence and risk factors of HIV associated INCPH.MethodsAll adult HIV patients attending the outpatient clinic between February and September 2011 underwent sonographical spleen size determination and assessment of portosystemic collaterals. Patients with splenomegaly underwent an extensive ultrasound examination. Gastroscopy was performed when additional signs of portal hypertension or collaterals were observed. All children with HIV infection underwent extensive ultrasound examination. INCPH was diagnosed according to the general definition. Differences between INCPH cases (group 1) and HIV patients treated with didanosine (ddI) without portal hypertension (group 2) were assessed at HIV diagnosis, start of ddI and INCPH diagnosis.Summary of resultsFour out of 1010 screened adult HIV patients were diagnosed with INCPH (prevalence of 4‰). Hundred of the 1010 screened patients were treated with ddI. All INCPH patients were treated with ddI, representing an INCPH prevalence of 4% in patients exposed to ddI. In The Netherlands, 7000 patients were treated with ddI and only 17 are diagnosed with INCPH, suggesting underdiagnosis in 260 patients. No differences in clinical characteristics predictive for the development of INCPH could be demonstrated between group 1 and group 2 at HIV infection or start of ddI treatment. INCPH patients were treated longer with ddI [86 vs. 51 months, p<0.01] and concomitant treatment with ddI and stavudine [21 vs. 4 months, p<0.01]. Corrected for age and duration of follow‐up of HIV, active protein c [0.64 vs. 1.13, p<0.01] and active protein s [0.67 vs. 1.01, p<0.01] levels were lower in the INCPH group. None of the 38 children with HIV infection were diagnosed with INCPH. None of these children were ever treated with ddI.ConclusionsIn our study HIV‐associated INCPH only occurred in patients exposed to ddI. Awareness for this disorder is warranted considering the suggested underdiagnosis based on these study results. Risk factors are long term treatment with ddI and concomitant treatment with stavudine and screening for signs of portal hypertension in this subgroup may be recommended. A possible pathophysiological role for thrombophilia remains to be elucidated.
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Systematic Processing of β‐Tricalcium Phosphate for Efficient Protein Loading and In Vitro Analysis of Antigen Uptake
Authors: Ozhukil Kollath Vinayaraj , De Geest Bruno G. , Mullens Steven , De Koker Stefaan , Luyten Jan , Persoons Rosita , Traina Karl , Remon Jean Paul , Cloots Rudi 
Published: November 2012

AbstractMicroparticulate calcium phosphate (CaP) powders are promising drug carriers because of their biocompatibility and degradability under physiological conditions. The adsorption capability of CaP microparticles makes them interesting candidates, within the inorganic carrier materials, for delivering protein antigens to professional antigen presenting cells (APC) for vaccination purpose. However, in order to bind and deliver a sufficient amount of protein, the challenge is to effectively increase the binding capacity of this material. In this study, β‐tricalcium phosphate (β‐TCP) powder is engineered to obtain microparticles with increased protein loading, using bovine serum albumin as a model antigen. The decrease in particle size and increase in specific surface area of carrier is shown to strongly affect protein adsorption. Finally, we demonstrate that the processed β‐TCP is capable of delivering its protein payload in vitro to dendritic cells, which are professional APCs and the target cell population for microparticulate vaccines.
Simulation study of the morphologies of energetic block copolymers based on glycidyl azide polymer
Authors: Yang Zhou , Xin‐Ping Long , Qing‐Xuan Zeng 
Published: November 2012

AbstractThe morphologies of energetic block copolymers based on glycidyl azide polymer (GAP) were investigated by dissipative particle dynamics simulation. The results show that the morphologies could be used to qualitatively explain the variation in the mechanical properties of poly(azidomethyl ethylene oxide‐b‐butadiene) diblock copolymers (DBCs) and that bicontinuous (B) phases could effectively improve the mechanical properties. Among our designed DBCs, only GAP–acrylic acid, GAP–acrylonitrile, and GAP–vinyl amide could form B phases at very narrow regions of GAP contents. The triblock copolymers with their linear topologies could maintain the B phases in the broader region of GAP contents. We hope these results can provide help in the design and synthesis of new energetic block copolymers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013