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。     

HIV/HBV/HCV共感染者CD4＋、CD_8＋T淋巴细胞计数的对比分析

目的研究HIV/HBV/HCV共感染者外周血CD4＋、CD8＋T淋巴细胞计数变化,探讨共感染对HIV感染进程及患者机体免疫功能的影响。方法对75例HIV共感染样本进行外周血CD4＋、CD8＋T淋巴细胞计数测定并进行分析。结果 4组的CD4＋T淋巴细胞计数比较差异无统计学意义（P〉0.05）;4组的CD8＋T淋巴细胞计数及CD4＋/CD8＋比较差异有统计学意义（P〈0.05）。结论共感染会影响患者外周血CD8＋T淋巴细胞计数及CD4＋/CD8＋比值,HIV/HBV/HCV三重感染患者的CD8＋T淋巴细胞计数较其他组高。     

慢性乙肝合并艾滋病病毒感染的抗病毒治疗分析

目的研究依非韦伦（EFV）＋替诺福韦（TDF）＋拉米夫定（3TC）三联疗法治疗慢性乙肝（HBV）合并艾滋病（HIV）的临床疗效。方法 HBV合并HIV患者21例,采用EFV＋TDF＋3TC联合进行HBV并HIV的抗病毒治疗,通过治疗前后的病毒学及生化指标变化等评价其临床疗效。结果 21例患者治疗后第3、6、12个月,HIV-RNA、HBV-DNA病毒载量均低于检测下限。CD4＋T淋巴细胞计数则较治疗前均明显上升（P〈0.05）,治疗后12个月内,无新增肝肾功能损伤案例。结论 EFV＋TDF＋3TC抗病毒方案治疗HBV合并HIV能有效抑制病毒复制、提高机体免疫学应答上的高效性,安全性高,值得重视。     

胱抑素C等生化指标用于糖尿病肾病肾损害程度的适用性评价

目的 探讨血清胱抑素C（CysC）等生化指标在糖尿病肾病各期诊断中的临床适用性。方法 选取2012年11月—2013年3月于平煤神马医疗集团总医院住院治疗的141例2型糖尿病患者为研究对象,所有病例均采用1999年WHO标准,本实验依据24 h尿微量白蛋白排泄率（UAER）分为：正常白蛋白尿组38例,微量白蛋白尿组42例,少量白蛋白尿组35例,大量白蛋白尿组26例,同期选取46例健康体检者进行对照分析。结果 2型糖尿病肾病早期肾功能损害患者血清CysC、UAER明显高于正常对照组（P〈0.05）;2型糖尿病肾病早期肾功能损害患者血清CysC和UAER检出率比较,差异无统计学意义（P〉0.05）。结论 血清CysC和UAER在2型糖尿病肾病早期肾功能损害患者中的升高均较为灵敏,CysC测定方法简单且结果受年龄、饮食等因素干扰少,值得临床推广应用。     

HIV/AIDS患者T淋巴细胞变化情况及其临床意义

目的探讨HIV/AIDS免疫病理的改变特点,为AIDS防治工作提供科学依据。方法以71例HIV感染者和54例AIDS患者为研究对象,并选取140例健康体检者为对照组,检测分析3组外周血CD4＋、CD8＋T淋巴细胞的变化及其临床意义。结果 CD4＋细胞计数正常对照组[（670±361）个/μL]〉HIV组[（378±235）个/μL]〉AIDS组[（154±104）个/μL]（P〈0.01）;CD8＋细胞计数HIV组[（918±823）个/μL]明显高于正常成人组[（489±250）个/μL]与AIDS组[（512±319）个/μL]（P〈0.05）;CD4＋/CD8＋的比值正常成人组（1.48±0.89）明显高于HIV组（0.41±0.37）和AIDS组（0.18±0.16）（P〈0.05）。结论本地区HIV/AIDS患者T淋巴细胞亚群的变化过程与疾病进展有良好的相关性。     

HIV感染者和AIDS患者及正常人CD_4与CD_8细胞计数对照研究

目的研究正常人与艾滋病（AIDS）患者、人类免疫缺陷病毒（HIV）感染者之间免疫指标CD4细胞计数、CD8细胞计数及CD4/CD8比值的差异。方法使用BD公司CD4T细胞检测试剂对我院体检的43份正常人全血样本（正常组）,与随访检查的199例HIV感染者（感染组）及49例AIDS患者（患者组）的全血样本进行检测。结果正常组与患者组及感染组CD4细胞计数、CD8细胞计数、CD4/CD8比值之间差异有统计学意义（P〈0.05）,患者组、感染组CD4细胞计数、CD4/CD8比值显著低于正常组（P〈0.05）,CD8细胞计数显著高于正常组（P〈0.05）;患者组与感染组CD4细胞计数、CD4/CD8比值、CD8细胞计数差异无统计学意义（P〉0.05）。结论 HIV感染者、AIDS患者的CD4细胞计数、CD4/CD8细胞计数降低,而CD8细胞计数升高。     

一线ART治疗方案对HIV合并HBV感染患者的临床疗效观察

目的：探讨一线ART治疗方案对HIV合并HBV感染患者的临床疗效。方法选择2012年4月至2014年5月首诊治疗的46例HIV合并HBV感染患者,入组46例患者均采取一线ART治疗方案,分别于治疗前、治疗3个月、6个月、12个月检测患者CD4+T细胞计数变化、病毒转阴率以及肝功能变化情况,并记录患者治疗期间不良反应发生情况。结果治疗3、6、12个月,患者 CD4+T 细胞计数水平显著高于治疗前,差异有统计学意义( P <0.05),且随着治疗时间的延长,患者CD4+T细胞计数显著增加( P <0.05);治疗后患者丙氨酸氨基转移酶水平较治疗前显著降低( P <0.05),患者血肌酐水平较治疗前显著升高( P <0.05);随着治疗时间的延长,患者HIV RNA与HBV DNA病毒转阴率均显著增高( P <0.05),且治疗12个月,患者 HIV RNA 与 HBV DNA 病毒转阴率均达到100%。结论一线ART治疗方案能够有效提高HIV/HBV合并感染患者免疫功能、改善患者肝功能水平,对HIV、HBV病毒均能有效控制,且患者耐受性较好,安全可靠。     

新型冠状病毒肺炎患者血常规及淋巴细胞亚群的变化特点

目的 探讨新型冠状病毒肺炎（COVID-19）患者血常规及淋巴细胞亚群的变化。方法 选取2020年1 月—2 月在阜阳市第二人民医院收治的确诊 COVID-19 患者 66 例,将同期住院的疑似并最终排除新型冠状病毒 （SARS-CoV-2）感染的56例患者作为对照组。比较2组患者血常规和淋巴细胞亚群水平的差异,Logistic回归分析 COVID-19 患病的血液细胞学影响因素。结果 与对照组相比,COVID-19 组白细胞计数（WBC）、中性粒细胞 （NEU）、淋巴细胞（LYM）、CD4+ T细胞、CD8+ T细胞、B淋巴细胞水平均降低（P＜0.05）。Logistic回归分析显示,CD4+T 细胞水平升高是COVID-19患者的保护因素（OR=0.997,95%CI：0.994~0.999）,同时CD4+ T细胞与LYM计数呈正相关 （rs=0.829,P＜0.01）。结论 COVID-19患者外周血T淋巴细胞水平下降,淋巴细胞亚群分析可为临床诊断SARS-CoV-2的感染和治疗提供参考。     

急性脑卒中患者并发肾功能损害临床分析

目的 探讨急性脑卒中急性肾功能损害的相关因素及临床意义。方法检测发病1周内脑卒中患者肾功能即尿素氮、肌酐、尿酸，同时进行神经功能缺损程度评分（SSS）与对照组对比分析。结果脑出血（ICH）组和脑梗死（CI）组的肾功能损害发生率均高于对照组（P〈0．05），ICH组的肾功能损害发生率高于CI组（P〈0．05），脑卒中病变部分不同，肾功能损害发生率有差异，丘脑、颞叶损害组肾功能损害发生率均高于无丘脑、颞叶损害组（P〈0．05），肾功能损害的程度与SSS评分呈正相关，脑卒中的病变部位、程度、年龄、糖尿病、合并昏迷、感染、消化道出血、心功能损害、甘露醇及肾毒性抗生素应用与脑卒中患者发生肾损害密切相关。结论急性脑卒中存在明显的肾功能改变，多因素参与脑卒中合并肾功能损害，检测其肾功能有助于病情轻重及预后判断。     

糖尿病合并肺结核患者sFas／sFasL与T淋巴细胞的关系

目的观察糖尿病合并肺结核患者外周血sFas／sFasL和T淋巴细胞凋亡及其亚群的变化及在糖尿病合并肺结核发生发展中的作用。方法采用酶联免疫吸附实验（ELISA）检测各组外周血sFas和sFasL含量,用流式细胞仪分析淋巴细胞凋亡百分率。用单克隆抗体碱性磷酸酶标记法（APAAP）检测外周血CD3^＋、CD4^＋和CD8^＋ T淋巴细胞数量。结果肺结核、糖尿病和糖尿病合并肺结核患者外周血sFas、sFasL含量均明显高于正常对照组（P〈0．01）,糖尿病患者外周血sFasL含量明显高于其他组（P〈0．01）。糖尿病合并肺结核患者外周血sFasL含量明显低于糖尿病组（P〈0．01）。糖尿病合并肺结核组患者淋巴细胞凋亡率明显高于正常对照组及肺结核组。肺结核、糖尿病及糖尿病合并肺结核组患者与正常对照组相比较,外周血CD3^＋、CD4^＋T细胞降低。结论糖尿病合并肺结核患者存在细胞免疫功能失调,sFas／sFasL系统和T淋巴细胞在糖尿病合并肺结核的发病机制中起着重要的作用,外周血sFasL含量可作为鉴别糖尿病是否已合并肺结核的指标。     

Tenofovir induced Fanconi syndrome: A possible pharmacokinetic interaction

Tenofovir was introduced as a second line drug for the treatment of human immunodeficiency virus (HIV) infection in India in December 2009. Although rare, renal toxicity is a recognized adverse drug reaction (ADR) of this drug, especially when administered with boosted lopinavir-ritonavir. In this case, an HIV positive patient receiving tenofovir based antiretroviral therapy (ART) for last 1 year developed albuminuria, glycosuria and hypophosphatemia. Renal function tests and random blood sugar were within normal limits. He was diagnosed as a case of tenofovir induced Fanconi syndrome. Tenofovir was discontinued and patient was prescribed an alternate regimen. Five months later clinical symptoms and renal functions returned to normal. A pharmacokinetic interaction between tenofovir and ritonavir may have resulted in the toxicity. A periodic monitoring of renal functions is desirable in patients on tenofovir based ART.KEY WORDS: Adverse drug reaction, Fanconi syndrome, protease inhibitor, tenofovir     

High rate of reversibility of renal damage in a cohort of HIV-infected patients receiving tenofovir-containing antiretroviral therapy

We assessed the progress of renal damage after discontinuation of tenofovir (TDF) in patients who started therapy with normal renal parameters. Normal local reference values were as follows: estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation (MDRD), ?60mL/min/1.73m(2); creatinine, ?1.20mg/dL; serum phosphate: ?2.69mg/dL; proteinuria: <30mg/dL, and glycosuria: <20mg/dL in nondiabetic patients. A logistic regression analysis was used to evaluate factors related to normalization of renal function. We included 183 patients; 85% were male, and median (IQR) age was 44 (40-50)years. Time on TDF was 39 (22-63)months. After 22 (13-49.5)months from TDF discontinuation, renal parameters returned to normal values in 59% of patients, improved (without reaching normal values) in 9.8%, and did not improve in 31%. Median time until normalization was 4 (2-15.75)months, and time to maximum improvement in patients whose values did not return to normal was 14 (8.75-27.75)months. Follow-up was <12months in 30% of the patients who did not improve. The only factors significantly associated with normalization of renal parameters were nadir CD4 T-cell count (p=0.034; OR=1.002, per 1 cell of increase) and CD4 T-cell count at the end of therapy with TDF (p=0.030; OR=1.033, per 1 cell of increase). Reversibility of renal damage was prompt and complete in 59% of patients receiving TDF-containing regimens and was associated with a higher nadir and current CD4+ T-cell count, suggesting a role of preserved cellular immunity in renal recovery in this population.     

Renal function in HIV/HBV co‐infected and HBV mono‐infected patients on a long‐term treatment with tenofovir in real life setting

The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co‐infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono‐infected patients on long‐term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP‐binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co‐infected and 34 HBV mono‐infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real‐time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P<.01) that was not significantly different between the two study groups. Moreover, a significant decline in estimated glomerular filtration rate (eGFR) was observed from baseline (P<.01), and it was significantly greater in HBV mono‐infected than co‐infected patients (P=.03). The distribution of ABCC2, ABCC4 and ABCC10 genotypes among a subgroup of 34 patients did not show significant association with eGFR decline <90 mL/min per 1.73 m². Although our findings showed a statistically significant decrease in eGFR with long‐term use of TDF, its clinical impact seems to be modest. The role of genetic factors to identify patients at greater risk for developing tenofovir‐induced renal toxicity needs to be further investigated.     

Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen

Introduction: WHO recommends tenofovir, efavirenz, and lamivudine or emtricitabine for first-line antiretroviral therapy (ART) in adults, which replaced more toxic regimens using stavudine, zidovudine or nevirapine.

Areas covered: We searched Pubmed to identify observational studies and randomized controlled trials reporting toxicity of these antiretrovirals published between 2011 and 2016, and hand-searched abstracts presented at major HIV conferences in 2015 and 2016, focusing on data from sub-Saharan Africa. Tenofovir’s nephrotoxicity manifests as mild renal tubular dysfunction (common and of uncertain clinical significance), acute kidney injury (rare), and chronic declining glomerular filtration rate (common). African studies, which include high proportions of patients with renal dysfunction from opportunistic diseases, report population improvement in renal function after starting tenofovir-based ART. Tenofovir modestly decreases bone mineral density, and there is emerging data that this increases fracture risk. Efavirenz commonly causes early self-limiting neuropsychiatric toxicity and hypersensitivity rashes. Recent studies have highlighted its long-term neuropsychiatric effects, notably suicidality and neurocognitive impairment, and metabolic toxicities (dyslipidemia, dysglycemia, and lipoatrophy). We point out the challenges clinicians face in the recognition and attribution of adverse drug reactions.

Expert commentary: Tenofovir and efavirenz are generally well tolerated, but both are associated with potentially serious toxicities. Pharmacovigilance systems in resource-limited settings with high HIV burden should be strengthened.     

住院老年高血压患者的血糖改变及其对肾功能的影响

临床上,不少老年高血压患者尿常规检查尿蛋白为阴性,而患者出现不同程度的肾功能损害,这类问题国内外文献报道不多。本文旨在探讨老年高血压住院患者中尿蛋白阴性患者的血糖改变及其对肾功能的影响。     

不同程度慢性乙型肝炎患者肾功能评估及危险因素分析

目的 对不同程度慢性乙型肝炎（CHB）患者肾功能进行评估,分析正规抗病毒治疗对CHB患者肾功能的影响,分析CHB患者肾功能损伤的危险因素。方法 收集2015年1月至2016年4月于安徽医科大学第一附属医院379例CHB患者,按照CHB临床分度将患者分为轻度组（191例）、中度组（123例）、重度组（65例）3组,采用简化MDRD方程计算CHB患者肾小球滤过率（eGFR）。分析不同程度CHB患者肾功能有无差异,正规抗病毒治疗对不同程度CHB患者肾功能的影响及年龄、性别、HBeAg、HBV DNA等对CHB患者肾功能的影响。结果 轻度组患者eGFR水平为（73.10±14.42）mL/（min·1.73m²）,中度组患者eGFR水平为（65.17±11.42）mL/（min·1.73m²）,重度组患者eGFR水平为（59.72±18.59）mL/（min·1.73m²）,3组间eGFR水平差异具有统计学意义（F=25.200,P=0.000）;CHB患者肝炎病情程度和年龄是引起CHB患者出现肾功能损伤的危险因素（P<0.05）。结论 CHB患者eGFR水平与病情程度相关,轻度和中度正规抗病毒治疗的CHB患者eGFR水平较未正规抗病毒治疗者eGFR水平高,肝炎病情程度与年龄是引起CHB患者出现肾功能损伤的危险因素。     

Prevalence of anemia and correlation with biomarkers and specific antiretroviral regimens in 9690 human immunodeficiency virus-infected patients: findings of the Anemia Prevalence Study*

ABSTRACT

Objective: To describe anemia prevalence and correlates with biomarkers and antiretroviral therapy (ART) in HIV/AIDS.

Methods: Multicenter, cross-sectional study; clinical laboratory data collected at single visits, including hemoglobin (Hb), CD4⁺ count, HIV?1 RNA. Patients receiving care at US physician offices during the year 2000. Main outcome measure was anemia (Hb < 14?g/dL [men]; < 12?g/dL [women]) and marked anemia (Hb < 11?g/dL [men]; < 10?g/dL [women]) prevalence. Multivariable models examined association of anemia prevalence with HIV?1 biomarkers and ART.

Results: Among 9690 patients, prevalence of anemia and marked anemia was 36% and 5%, respectively. Among 1721 patients receiving no ART, 39.7% were anemic; among 7252 receiving highly active antiretroviral therapy (HAART), 35.5% were anemic (?p = 0.001). Anemia was most prevalent among men (37.3 vs. 32.3%; p?= 0.0008), blacks (49 vs. 26% [whites]; p < 0.0001), patients with CD4⁺ < 200 cells/mm³ (57 vs. 23% [≥ 500 CD4⁺]; p?< 0.00001), and HIV?1 RNA > 30?000 copies/ml (53 vs. 30% [< 500 copies/ml]; p?< 0.00001). Marked anemia was more common in women (6.8 vs. 4.3%; p?< 0.0001). Among treated patients, logistic regression analysis controlling for CD4⁺, HIV?1 RNA, sex, and ethnicity, zidovudine (ZDV)-containing regimens (except combination with saquinavir/ZDV/lamivudine) were associated with increased overall anemia risk (odds ratio, 1.39 : 1.74). No regimen was associated with increased risk for marked anemia. Multivariable logistic regression showed CD4⁺, sex, and ethnicity more strongly associated with anemia than any ART regimen.

Conclusion: This large, single-visit, cross-sectional, US-based study shows that anemia remains highly prevalent in HIV-infected patients. Data from this analysis suggest low CD4⁺ count, black ethnicity, and male sex are consistently strongest correlates of overall anemia; women are significantly more likely to have marked anemia.     

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function

Background The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug?Cdrug interaction. Objective The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. Setting One teaching hospital in the Netherlands. Method The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Main outcome measure Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. Results 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: ??combined use of a diuretic with a RAAS inhibitor?? which was higher in the control-group (62 vs. 43?%, p?=?0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95?% 0.3?C1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95?% 1.1?C5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50?ml/min/1.73?m². Conclusion Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50?ml/min/1.73?m²) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.