Guaranteed cost control for switched LPV systems via parameter and state‐dependent switching with dwell time and its application

This paper is concerned with the problem of guaranteed cost control for switched linear parameter‐varying (LPV) systems. A parameter and state‐dependent switching law with dwell time is designed. The guaranteed cost control problem for switched LPV systems is still solvable even though this problem for each subsystem is unsolvable. First, a sufficient condition ensuring the solvability of the guaranteed cost control problem for switched LPV systems is presented via multiple parameter‐dependent Lyapunov functions. Then, the parameter‐dependent controller is designed, such that the closed‐loop system is asymptotically stable with the guaranteed cost index. Finally, the effectiveness of the proposed control design scheme is illustrated by its application to an aero‐engine. Copyright © 2016 John Wiley & Sons, Ltd.     

初治使用含克立芝方案出现病毒学失败HIV/AIDS患者耐药情况分析

目的 分析初次使用含克立芝抗病毒治疗方案治疗艾滋病病毒感染者/艾滋病病人治疗失败基因型耐药情况。方法 收集云南省2014-2015年接受高效抗逆转录病毒治疗的艾滋病病毒感染者/艾滋病病人的临床及实验室资料,对初次使用含克立芝抗病毒治疗方案治疗且治疗持续6个月以上、病毒载量仍大于1 000Copies/ml的患者进行基因型耐药检测,分析耐药基因变异情况及耐药位点的变化情况。结果 2年共获得符合条件pol区序列150条,该人群中耐药发生率为27.3%(41/150)。在使用过的药物中,对3TC、TDF、D4T、AZT、ABC高度耐药的情况分别是16(10.7%)、2(1.3%)、1(0.7%)、0(0%)、3(2.0%),对蛋白酶抑制剂没有出现高度耐药的情况。结论 初治使用含克立芝治疗方案治疗失败的病人耐药率仍处于较低水平,但是随着使用含克立芝方案治疗人数增加以及治疗时间延长,仍需加强耐药检测。     

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized,controlled, phase 3, non-inferiority TALENT study

BackgroundAlbuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.MethodsWe carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.ResultsAt the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.ConclusionsThe TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02369965","term_id":"NCT02369965"}}NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx     

HIV protease inhibitors elicit volume-sensitive Cl current in cardiac myocytes via mitochondrial ROS

HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl⁻ current (I_Cl,swell) is activated by ROS, we tested whether HIV PI stimulate I_Cl,swell in ventricular myocytes. Ritonavir and lopinavir elicited outwardly rectifying Cl⁻ currents under isosmotic conditions that were abolished by the selective I_Cl,swell-blocker DCPIB. In contrast, amprenavir, nelfinavir, and raltegravir, an integrase inhibitor, did not modulate I_Cl,swell acutely. Ritonavir also reduced action potential duration, but amprenavir did not. I_Cl,swell activation was attributed to ROS because ebselen, an H₂O₂ scavenger, suppressed ritonavir- and lopinavir-induced I_Cl,swell. Major ROS sources in cardiomyocytes are sarcolemmal NADPH oxidase and mitochondria. The specific NADPH oxidase inhibitor apocynin failed to block ritonavir- or lopinavir-induced currents, although it blocks I_Cl,swell elicited by osmotic swelling or stretch. In contrast, rotenone, a mitochondrial e⁻ transport inhibitor, suppressed both ritonavir- and lopinavir-induced I_Cl,swell. ROS production was measured in HL-1 cardiomyocytes with C-H₂DCFDA-AM and mitochondrial membrane potential (ΔΨ_m) with JC-1. Flow cytometry confirmed that ritonavir and lopinavir but not amprenavir, nelfinavir, or raltegravir augmented ROS production, and HIV PI-induced ROS production was suppressed by rotenone but not NADPH oxidase blockade. Moreover, ritonavir, but not amprenavir, depolarized ΔΨ_m. These data suggest ritonavir and lopinavir activated I_Cl,swell via mitochondrial ROS production that was independent of NADPH oxidase. ROS-dependent modulation of I_Cl,swell and other ion channels by HIV PI may contribute to some of their actions in heart and perhaps other tissues.     

三种常用高效抗逆转录病毒治疗方案疗效的比较

目的：比较替诺福韦酯（tenofovir disoproxil fumarate,TDF）+拉米夫定（lamivudine,3TC）+依非韦伦（efavirenz,EFV）、替诺福韦酯+拉米夫定+克力芝（lopinavir/ritonavir,LPV/r）、齐多夫定（zidovudine,AZT）+拉米夫定+依非韦伦3种高效抗逆转录病毒治疗（highly active anti-retroviral therapy,HAART）方案的疗效。方法：回顾性收集2011年1月至2021年4月在广西中医药大学附属瑞康医院治疗的HIV感染者/艾滋病患者220例,按治疗方案分为3组,其中TDF+3TC+EFV （A组）136例、TDF+3TC+LPV/r （B组）53例、AZT+3TC+EFV （C组）31例。比较不同组治疗1年、2年后的CD4⁺、CD8⁺T细胞计数和病毒载量（HIV RNA）的变化,并计算各组的用药成本。结果：治疗1年和2年后,各组CD4⁺T细胞计数、CD4⁺/CD8⁺T细胞比值均显著升高（P<0.05）;CD8⁺T细胞计数均有所下降,其中A组治疗前后差异有统计学意义（P<0.05）;HIV RNA在最低检测限以下的患者达96%以上;病毒学指标和免疫学指标的组间差异均无统计学意义（P>0.05）。结论：TDF+3TC+EFV、TDF+3TC+LPV/r、AZT+3TC+EFV三种方案的疗效相近,其中,TDF+3TC+EFV有成本低、安全性高的优势。     

Acquired macroglossia due to lopinavir/ritonavir treatment

A HIV-positive patient, 3 months after the treatment initiation with lopinavir-/ritonavir (LPV/r) acquired macroglossia. The tongue biopsy revealed mature adipose tissue accumulated into submucosa. The drug was discontinued and the patient showed a significant improvement. This case is the first case in the medical literature of acquired macroglossia because of LPV/r, a drug causing changes in body fat composition.     

Portal Vein Embolization before Right Hepatectomy or Extended Right Hepatectomy Using Sodium Tetradecyl Sulfate Foam: Technique and Initial Results

PurposeTo evaluate the safety and efficacy of portal vein embolization (PVE) with sodium tetradecyl sulfate (STS) foam.Materials and MethodsA single-center retrospective review of 35 patients (27 men and 8 women; mean age, 61 y) who underwent PVE with STS foam was performed. The technical success rate, rate of PVE at producing adequate future liver remnant (FLR) hypertrophy, and rate of disease progression precluding resection after PVE were analyzed. Complications of PVE and liver resection after PVE were recorded.ResultsPVE was performed on 35 patients before right hepatic resection for both primary and secondary hepatic malignancies (22 hepatocellular carcinoma, 10 metastasis, 2 cholangiocarcinoma, 1 invasive gallbladder carcinoma). Technical success was achieved in 97.1% (34 of 35) of patients. Mean FLR of the total estimated liver volume increased from 24.5% (SD, 7.7%) to 36.5% (SD, 14.5%), a mean percentage increase of 48.8% (SD, 34.3%). PVE produced adequate FLR hypertrophy in 31 of 35 patients (88.6%). Proposed right hepatectomy was subsequently performed in 27 patients (77.1%). One patient remains scheduled for surgery, two had peritoneal spread at surgery and resection was aborted, two had disease progression on imaging after PVE, and three had inadequate FLR hypertrophy with no surgery. One major complication was observed related to PVE that involved nontarget embolization to segment III, which was managed conservatively.ConclusionsPreoperative PVE with STS foam is a safe and effective method to induce hypertrophy of the FLR.     

含克力芝组合的HAART方案对HIV/HCV混合感染的疗效探讨

目的探讨含克力芝(LPV/r)组合的高效抗反转录病毒治疗(HAART)方案,对艾滋病病毒(HIV)、丙型肝炎病毒(HCV)混合感染治疗的效果。方法采用前瞻性研究方法,选择HIV/HCV混合感染患者43例,通过Spw-Pb网络数据平台随机分为研究组与对照组。研究组22例,采用以洛匹那韦/利托那韦(LPV/r)为基础的HAART治疗方案;对照组21例,采用以依非韦伦(EFV)为基础的HAART治疗方案。研究组与对照组检测基线CD4+T淋巴细胞计数、HIV病毒载量、丙氨酸转氨酶(ALT)、胆固醇(CHO)、甘油三酯(TG)等指标;治疗后48周分别检测上述指标,研究终点为48周。观察病毒学、免疫学、ALT、CHO、TG等指标的变化。结果 HAART治疗48周,研究组与对照组HIV-RNA阴转率比较差异无统计学意义(P>0.05)。研究组与对照组基线CD4+T淋巴细胞、ALT、CHO、TG比较差异无统计学意义(均P>0.05);HAART治疗48周,研究组CD4+T淋巴细胞计数增长明显高于对照组,差异有统计学意义(P<0.05);而研究组与对照组ALT、CHO、TG比较差异无统计学意义(均P>0.05)。结论含LPV/r组合的抗病毒方案对HIV/HCV混合感染治疗效果较优越,CD4+T淋巴细胞增长较明显,胆固醇、甘油三酯变化不大,建议HIV/HCV混合感染HAART治疗选择LPV/r方案为佳。     

Delay-dependent robust control of stochastic systems with convex polynomial uncertainty

This article addresses a robust control problem of time-varying stochastic systems with time-delays. Through Linear Parameter Varying (LPV) modeling approach, the time-varying parameters can be described via the convex combination. Therefore, the LPV stochastic system is interpreted by a weighting function and multiplicative noised linear systems. Furthermore, stabilization problem for the systems is investigated via Gain-Scheduled (GS) technique to increase robustness. For the problem, some sufficient conditions are derived by Integral Lyapunov-Krasovskii Function (ILKF) such that the conservatism caused by derivative of weighting function is ignored. Besides, an Iterative Linear Matrix Inequality algorithm is used to determine the auxiliary variable such that the problem can be solved via the convex calculation. Finally, some simulations are provided to demonstrate effectiveness and applicability of this article.