86例HIV感染患者的肾功能状态与危险因素分析

目的：分析HIV患者肾功能状态与危险因素,深化对该人群肾损害风险的认识。方法收集HIV患者临床资料,包含年龄、性别、高血压和糖尿病病史、感染途径、抗逆转录病毒治疗（ ART）等,检测血常规,完善外周血CD4淋巴细胞计数、乙肝表面抗原定性、抗丙型肝炎病毒抗体定性和HIV?RNA定量分析,运用血肌酐值估算肾小球滤过率（ eGFR）,Logistic回归分析各因素与肾功能状态的相关关系。结果86例黑人HIV患者,女性20例（23．3％）,年龄（45．3±10．7）岁,eGFR水平（74．9±23．4）mL／（min·1．73m2）。肾功能损害25例,肾功能正常61例。肾功能损害组患者年龄、高血压与糖尿病比例、WHO临床分期和基线HIV?RNA定量均显著高于肾功能正常组患者,而Hb、入院CD4淋巴细胞计数和eGFR水平均显著低于肾功能正常组患者（P均＜0．05）。肾功能正常组含替诺福韦（TDF）方案的患者eGFR水平显著低于未含 TDF方案的患者（P＜0．05）。多因素Logistic回归分析显示HIV患者肾功能损害的独立相关因素为年龄≥50岁、合并糖尿病和WHO临床分期。结论除传统危险因素外,HIV感染及某些ART药物均可能与HIV患者肾功能损害有关。     

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。     

替诺福韦酯治疗多重耐药慢性乙型肝炎的回顾性分析

目的:观察替诺福韦酯(TDF)治疗多重耐药慢性乙型肝炎(CHB)的短期疗效及不良反应。方法:回顾性分析32例多重耐药CHB患者病历资料,所有患者治疗前均进行乙型肝炎病毒(HBV)耐药基因检测,存在多位点耐药,并给予TDF口服治疗。观察TDF治疗前、后丙氨酸氨基转移酶(ALT)复常率、HBV-DNA阴转率、乳酸、肾功能等指标。结果:治疗第3个月时,ALT复常率达100%,治疗半年时HBV-DNA阴转率达96.88%,治疗中患者未出现乳酸水平升高及肾功能异常。结论:TDF治疗多重耐药CHB疗效迅速,未出现明显不良反应。     

HIV感染/艾滋病患者富马酸替诺福韦二吡呋酯相关范可尼综合征临床特征分析

目的探讨HIV感染/艾滋病(HIV/AIDS)患者富马酸替诺福韦二吡呋酯(TDF)相关范可尼综合征(FS)的临床特征。方法检索医院信息系统, 收集2017年12月至2021年2月在云南省传染病医院住院且采用含TDF的抗反转录病毒治疗(ART)并诊断为FS的HIV/AIDS患者的病历资料, 包括性别、年龄、体重、体重指数(BMI)、ART治疗方案和时间、诊断FS时间、主要临床表现、入院及出院实验室检查结果, 双能X射线骨密度检查结果以及干预和转归等信息, 进行回顾性分析。结果设定时段内诊断为TDF相关FS的HIV/AIDS患者共16例, 其中完全型FS 6例, 不完全型FS 10例;7例合并慢性丙型肝炎、高血压病、肝癌和抑郁症等慢性疾病;16例患者接受含TDF的ART治疗时间最短20个月, 最长168个月, 平均68个月;FS的初始症状多为骨痛、乏力、恶心、纳差、多饮、多尿, 体重下降等, 从出现初始症状至确诊FS的时间最短2周, 最长24周, 平均7周。实验室检查结果显示, 16例患者在血糖正常情况下尿葡萄糖均为阳性, 14例尿蛋白阳性, 低尿磷、低尿钙、低尿钾和低尿钠者分别为11、1...     

人类免疫缺陷病毒/获得性免疫缺陷综合征患者高效抗逆转录病毒治疗中发生骨髓抑制相关因素分析

目的:探讨HIV/AIDS患者高效抗逆转录病毒治疗(HAART)过程中出现骨髓抑制的高危因素。方法:回顾性分析432例HIV/AIDS患者HAART治疗资料,分别对患者的性别、年龄、HIV感染途径、体质量、是否肝、肾功能损害、HAART治疗疗程、HAART治疗方案、基线CD4⁺ T淋巴细胞数、是否合并机会性感染、是否联合应用具有骨髓抑制作用药物等与骨髓抑制的发生进行相关性分析。结果:骨髓抑制的发生与患者HIV感染途径、体质量无相关性(P> 0.05);与患者年龄、性别、肝、肾功能损害、HAART治疗疗程、HAART治疗方案、基线CD4⁺ T淋巴细胞数、联合应用具有骨髓抑制作用药物相关(P< 0.05)。结论:老年、女性、肝、肾功能损害者、HAART治疗疗程、HAART治疗方案、基线CD4⁺ T淋巴细胞数、合并机会性感染、联合应用具有骨髓抑制作用药物是患者治疗期间发生骨髓抑制的高危因素。     

膦甲酸与电解质紊乱

膦甲酸(foscarnet,可耐)是一种抗病毒药物,主要用于治疗疱疹类病毒、HIV和HBV等感染.据近年国外资料报道,该药可引起过敏反应、肾功能损害和电解质紊乱等.现将Reactions数据库1991～2000年国外应用膦甲酸引起电解质紊乱的病例综合报道如下.     

替诺福韦治疗艾滋病导致的范可尼综合征回顾性分析

目的:分析替诺福韦(TDF)治疗艾滋病导致的范可尼综合征(FS)的影响因素和预后。方法:对2014年1月-2016年9月发生的64例TDF相关的FS进行统计、分析。结果:FS发生率为2.08%,大部分在使用TDF 2~4年内发生,主要表现为电解质紊乱、尿蛋白和尿糖高,51.56%的患者合并肾小球滤过率下降,37.50%的患者合并骨质疏松。FS好发人群以年龄大、体质量低和合并有基础疾病为主。停用TDF和对症治疗后大部分好转,4例经过1年治疗无缓解。结论:使用TDF要定期监测肾功能、尿常规和电解质,发现FS要及时治疗。     

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。     

药物警戒

研究发现替诺福韦酯联合治疗引起肾损害 美国研究者认为,对于正在使用替诺福韦酯(tenofovir disoproxil fu-marate)治疗HIV感染的患者,联合使用安泼那韦(Amprenavir)和去羟肌苷(didanosine)与肾功能损害风险增加有明显相关性.     

406例脑卒中患者并发急性肾功能损害的临床观察

目的：探讨脑卒中患者并发急性肾功能损害的相关因素及临床意义。方法：对急性脑卒中患者进行肾功能的临床观察,并对其发生率作分析。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）,脑卒中病变部位不同,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其他部位损害组（P〈0.05）,脑卒中的病变部位与程度、年龄、患有糖尿病和高血压等肾相关退行性病变、合并意识障碍、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,观察其肾功能及尿量变化有助于病情轻重及预后判断,在治疗中做到早预防,早诊断。     

Nephrotoxicity Associated with Concomitant Use of Ledipasvir‐Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

Direct‐acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, with superior efficacy and safety compared to interferon‐based therapies. Despite these improvements, drug interactions with DAAs exist and may be clinically relevant in human immunodeficiency virus (HIV)‐coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (TDF) and ledipasvir‐sofosbuvir (LDV‐SOF). A 56‐year‐old woman with HIV infection who had been taking efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) for 6 years developed acute kidney injury 8 weeks after initiating LDV‐SOF for the treatment of HCV infection. Her serum creatinine concentration peaked at 10 mg/dL, compared with her baseline concentration of 0.9–1 mg/dL. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both LDV‐SOF and TDF were discontinued, and the patient's serum creatinine concentration decreased to 1.3 mg/dL over the following 6 weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and TDF, which results in increased TDF exposure. Despite knowledge of this interaction, LDV‐SOF is commonly prescribed in patients with HIV‐HCV coinfection, as patients who received LDV‐SOF– and TDF‐containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from TDF toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both LDV‐SOF and TDF. Clinicians prescribing LDV‐SOF to HCV‐HIV–coinfected patients receiving TDF should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative DAAs may also have a role in the management of patients at high risk for renal adverse effects from TDF.     

HIV/HBV抗病毒治疗药物的不良反应

目的:介绍抗HIV/HBV病毒药物的不良反应,指导临床工作者早发现、早处理。方法:总结PubMed数据库及万方数据库近10年来35篇有关抗病毒药物不良反应的文章。结果:依非韦伦(efavirenz,EFV)常见的不良反应为中枢神经系统毒性、皮疹、脂代谢异常。替诺福韦(tenofovir,TDF)具有潜在肾毒性,主要导致肾小管损伤。阿德福韦酯(adefovir dipivoxil,ADV)的结构与TDF相似,均可导致肾毒性。蛋白酶抑制剂(protease inhibitorsPIs)主要不良反应为代谢综合征。拉米夫定(lamivudine,3TC)的不良反应事件少见,少数发生严重皮疹。结论:不同类型抗病毒药物具有不同的不良反应。     

Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection

Introduction: In April 2017 tenofovir alafenamide (TAF) was added to the list of first-line therapies recommended for chronic hepatitis B (CHB). TAF has pharmacology similar to tenofovir disoproxil fumarate (TDF) with higher cell delivery to the hepatocytes but less systemic exposure.

Areas covered: We review here studies leading to TAF’s approval and comparing it to TDF. In two major clinical trials, TAF was non-inferior to TDF in achieving HBV DNA levels below 29 IU/ml. TAF-treated patients had significantly smaller decreases in bone mineral density (BMD) at the hip and spine in both HBeAg-positive and HBeAg-negative patients, and smaller mean increases in serum creatinine, although the difference was only statistically significant in HBeAg-positive patients. Patients treated with TDF for 96 weeks and then switched to TAF had improvements in renal and BMD measures only 24 weeks after switching.

Expert commentary: With clear evidence from major studies showing that TAF is safe, tolerable, and non-inferior to TDF, its recommendation as a first-line therapy is appropriate. Longer term follow up will be required to determine if the differences in adverse bone and kidney effects seen with TAF in comparison to TDF will be clinically relevant.     

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.     

Pre-exposure chemoprophylaxis of HIV infection: Quo vadis?

The pre-exposure chemoprophylaxis (now commonly referred to as PrEP) of HIV infection has gained increased momentum, concomitantly with the successful use of combination drug regimens for the treatment of AIDS. A pivotal component in the current drug combination regimens for the treatment of AIDS as well as the ongoing PrEP trials is tenofovir disoproxil fumarate (TDF, Viread^®) and its combination with emtricitabine (FTC). The combination of TDF with FTC has been marketed as Truvada^®. TDF and TDF/FTC has proven effective, if orally administered daily or intermittently, in the prevention of rectal simian human immunodeficiency virus (SHIV) infection in macaques. Topical tenofovir gel has proven effective in the prevention of HIV infection in women in South Africa. Oral TDF/FTC has proven effective in the prevention of HIV infection in men having sex with men, and recent press releases divulged that oral TDF/FTC is also effective in preventing HIV infection in serodiscordant couples in Botswana, Kenya and Uganda. Other PrEP studies are still ongoing. Available data point to the efficacy and safety of TDF with or without FTC in the prophylaxis of HIV infection (AIDS).     

Elvitegravir,cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults

Introduction: Tenofovir alafenamide (TAF) is is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations as compared to tenofovir disoproxil fumarate (TDF) and such property suggests that TAF-containing regimens can improve renal and bone safety compared with TDF-containing regimens. Single tablet regimen elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) is the first coformulation that includes TAF in place of TDF. This review aims to provide an overview of its role in the treatment of HIV infection.

Areas covered: This review covers pre-clinical and clinical data serached through Medline and Pubmed up to August 2015.

Expert opinion: In terms of efficacy, E/C/F/TAF was found to be non inferior to E/C/F/TDF in naive patients, and more effective in patients switching from TDF-based regimens with efavirenz or boosted PI. In safety analyses, E/C/F/TAF was constantly found to be associated with significant improvement of renal function and urinary markers of proximal tubulopathy, and significant improvement of bone mineral density (BMD) as compared to TDF-containing regimens. E/C/F/TAF, as a new single tablet regimen, appeared to be promising for optimization of cART tolerability in HIV-infected patients.     

The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis

BackgroundThe purpose of this study was to assess the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis. MethodsThe electronic databases of PubMed, the Cochrane Library, Nature, CNKI and WanFang data were searched. The key words were: (“tenofovir”, “entecavir”) and (“Chronic Hepatitis B” or “CHB”) and “Liver cirrhosis”. Heterogeneity and report bias were analyzed.ResultsThere was significant difference of ALT norm level in the short-term period of 3 months (RR = 1.43, 95%CI: 1.06–1.94, P < 0.017) and 6 months (RR = 0.89, 95%CI: 0.81–0.97, P < 0.017), and significant difference of undetectable HBV-DNA only in 3 months follow-up period (RR = 1.59, 95%CI: 1.04–2.42, P < 0.017) between TDF and ETV, but no significant difference in the long-term period. There is significant difference between TDF and ETV in eGFR level (RR = 1.601, 95%CI: 1.035–2.478, P = 0.0034) and hypophosphatemia incidence (RR = 4.008, 95%CI: 1.485–10.820, P = 0.006).ConclusionTDF has a better efficacy than ETV in 3 months treatment duration, but intriguingly, TDF might not better than ETV during the 6 months treatment period in the viral suppression and liver function improvement. There's no significant difference between TDF and ETV in the long-term treatment duration and in the treatment of HBV related liver cirrhosis. Both TDF and ETV could influence renal function but patients under TDF therapy may have more risk to suffer from renal damage and hypophosphatemia.     

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.