抗逆转录病毒治疗,高效

摘要： 目的 了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染/艾滋病(acquired immunodeficiency syndrome,AIDS)患者前列腺组织病毒储存库的情况,以及高效抗反转录病毒治疗(highly active anti-retroviral therapy,HAART)对HIV 感染/AIDS 患者前列腺组织中HIV-1 DNA 表达的影响.方法 纳入2017年7月至2019年10月广州市第八人民医院收治的前列腺增生合并HIV感染需要行手术治疗的12例患者,收集患者的血液和前列腺组织标本,分别检测患者血浆HIV-1 RNA、外周血CD4+T淋巴细胞计数和前列腺组织HIV-1 DNA水平.统计学分析采用独立样本t检验或曼-惠特尼U检验.结果 12例患者中,6例尚未开始进行HAART的患者CD4+T淋巴细胞计数为(519.8±121.5)/μL,前列腺HIV-1 DNA为2 602(365,10 700)拷贝/106细胞数;6例经HAART超过6个月患者的CD4+T淋巴细胞计数为(182.8 ±69.7)/μL,前列腺HIV-1 DNA为144(36,563)拷贝/106细胞数,两组患者的CD4+T淋巴细胞计数和前列腺HIV-1 DNA水平差异均有统计学意义(t =-5.889,Z=-2.082;均P＜0.05).结论 无论HIV感染/AIDS患者是否接受过HAART,前列腺组织均可作为HIV-1储存库.HAART进行免疫功能重建后,可以降低前列腺组织病毒储存库的大小.

摘要： 自1981年报道全球首例艾滋病患者以来,艾滋病的防治已经走过了 40个年头.随着高效抗反转录病毒治疗——"鸡尾酒"疗法的发现、推广和不断改进,人类免疫缺陷病毒感染者的生存和预后已得到了显著改善.随之而来的非艾滋病相关性疾病的发病率逐渐升高,越来越成为影响患者临床结局的重要因素.后"鸡尾酒"疗法时代的到来对艾滋病的临床诊治提出了新的问题和挑战.本研究简要回顾了全球艾滋病治疗和研究的现状,并阐述了当前我国艾滋病临床诊治研究中面临的个体化方案与多学科诊治、治疗简化与耐药应对,以及功能性治愈与慢性炎症控制等关键问题.

摘要： 目的 探讨重庆市主城区在治人类免疫缺陷病毒(HIV)感染者/获得性免疫缺陷综合征(AIDS)患者服药依从性及其影响因素,为制定提高HIV/AIDS服药依从性措施提供科学依据.方法 2017年7月1日至8月31日采用问卷调查方式对重庆市主城区在治、前来领药的HIV/AIDS进行调查,并对其服药依从性及影响因素进行分析.结果 共调查重庆市主城区在治HIV/AIDS 386例;年龄18～78岁,中位年龄33岁;男女性别比5.7:1;未婚者199例(51.6％);以大专及以上文化程度为主[48.2％(186/386)].90.7％(350/386)服药依从性良好,年龄越大、工作年限越长是依从性的保护因素[优势比(OR)=0.3、0.2,95％ 可信区间(95％CI):0.1～0.8、0.1～0.9];接受治疗时间越长是依从性的危险因素(OR=3.7,95％CI:1.6～8.7).结论 重庆市主城区在治(HIV/AIDS)服药依从性整体水平较高,为进一步巩固与提高,建议加强接受治疗时间较长的HIV/AIDS的服药依从性教育;加强无业人员和50岁以下人员的服药依从性教育和管理,强调对服药质量的监管.

摘要： 目的 探讨集中管理模式下艾滋病患者高效抗反转录病毒治疗依从性的影响因素,以及针对影响因素进行全程护理干预的效果.方法 选取集中管理模式下愿意接受规范高效抗反转录病毒治疗(HAART)治疗的艾滋病患者110例,对患者住院期间的治疗依从性进行评估和分析,并对其中的68例曾有过抗病毒治疗史的艾滋病患者住院前的依从性和影响因素进行评估,针对影响因素,对110例艾滋病患者HAART治疗期间进行全程的护理干预,并分析干预效果.结果 集中管理模式下艾滋病患者的治疗依从性,受到患者的负性情绪、社会家庭支持、伴随疾病、不良反应、HAART治疗效果等因素影响.110例艾滋病患者住院以后接受规范HAART治疗期间依从性好的有75例,占68.1％;68例住院前有抗病毒治疗史的患者,住院前治疗好的有41例,占60.3％.住院期间经全程护理干预后,依从性好的为55例,占88.9％.结论 集中管理模式下的艾滋病患者通过全程护理干预可以使其HAART治疗的依从性提高,同时较好的依从性对提高HAART治疗的疗效有重要意义.

摘要： 目的 分析干扰素λ3基因(IFNL3)/干扰素λ4基因(IFNL4)单核苷酸多态性(SNPs)对HIV-1感染患者应用高效抗逆转录病毒治疗(HAART)的影响.方法 收集2015年6月至12月浙江大学医学院附属第一医院应用HAART≥1年的63例HIV-1成年患者.采用定量聚合酶链反应(qPCR)定量检测患者血浆HIV-1 RNA、外周血单个核细胞(PBMC)的HIV-1 DNA水平和外周血SNPs.应用磁珠法检测血浆炎性细胞因子水平,并采用流式细胞仪检测外周血CD4 +T和CD8 +T淋巴细胞计数.根据抗病毒治疗应答情况将患者分为HIV-1 RNA低表达组(<100拷贝/mL)和高表达组(≥100拷贝/mL);根据淋巴细胞计数将患者分为CD4 +T淋巴细胞低表达组(<250个/μL)和高表达组(≥250个/μL);根据外周血HIV-1 DNA水平将患者分为HIV-1 DNA低表达组(<100拷贝/106个细胞)和高表达组(≥100个拷贝/106个细胞).分析IFNL3/IFNL4的SNPs、炎性细胞因子在HIV-1 RNA、HIV-1 DNA和CD4 +T淋巴细胞各亚组的分布和水平,以及SNPs与炎性细胞因子的关系.采用SPSS 18.0软件对数据进行分析.结果 rs368234815、rs8099917和 rs4803223在HIV-1 RNA低表达组和高表达组的分布差异具有统计学意义(χ2=0.043、0.047和0.032,P值均<0.05).IL-10在HIV-1 RNA低表达组较高表达组下降(U=4.00,P<0.05);IL-13水平在HIV-1 RNA高表达组和HIV-1 DNA高表达组较相对应组下降(U=0.00和2.00,P<0.05);IL-21水平在HIV-1 RNA高表达组及CD4 +T淋巴细胞低表达组较相对应组下降(U=3.00和2.00,P<0.05); IL-28A水平则在HIV-1 RNA高表达组、HIV-1 DNA高表达组和CD4 +T淋巴细胞低表达组均下降(U=3.00、0.50和3.00,P<0.05或 <0.01).此外,rs368234815与 IL-21相关(H =6.690,P <0.05),IL-21在rs368234815ΔG/ΔG[131.88(2.66,174.00)]亚型的表达高于 TT/TT[6.79(2.81, 26.48)](P <0.05);rs4803223与IFN-γ相关(H=6.690,P<0.05),IFN-γ在GG亚型[62.26(19.45,96.49)]中的表达要高于GA亚型[6.98(2.19, 99.14)](P<0.05).结论 IFNL3/IFNL4的rs368234815, rs8099917和rs4803223可能与HIV-1患者应用HAART治疗效果、炎性因子表达相关,并可能影响HAART疗效.%Objective To investigate the associations of IFNL3/IFNL4 single-nucleotide polymorphisms(SNPs)with the efficacy of highly active antiretroviral therapy(HAART)in patients with HIV-1 infection.Methods Sixty-three adult patients with HIV-1 infection receiving HAART for at least 1 year in the First Affiliated Hospital, Zhejiang University School of Medicine were enrolled.HIV-1 RNA loads in plasma and HIV-1 DNA loads in peripheral blood mononuclear cells(PBMCs),and blood SNPs were detected by quantitative polymerase chain reaction(qPCR).Plasma inflammatory cytokines were examined by magnetic beads method,and the CD4 +T and CD8 +T lymphocyte counts in peripheral blood were measured by flow cytometry.According to response to HAART,the patients were classified as low HIV-1 RNA group(viral load <100 copies/mL)and high HIV-1 RNA group(viral load≥100 copies/mL);according to CD4+T lymphocyte counts,the patients were defined as low CD4+T cell group(<250 cells/μL), and high CD4+T cell group(≥250 cells/μL);according to HIV-1 DNA levels,the patients were divided into low(<100 copies/106cells)and high(≥100 copies/106cells)HIV-1 DNA groups.Results Three candidate SNPs rs368234815,rs8099917 and rs4803223 had significantly different distribution between low and high HIV-1 RNA groups(χ2=0.043,0.047 and 0.032,all P<0.05).The levels of interleukin(IL)-10 were declined in the low HIV-1 RNA group(U=4.00,P<0.05);the levels of IL-13 were decreased in the high HIV-1 RNA group and the high HIV-1 DNA group(U=0.00 and 2.00,both P<0.05);the levels of IL-21 were reduced in the high HIV-1 RNA group and in the low CD4 +T cell group(U=3.00 and 2.00, both P<0.05),the levels of IL-28A were decreased in the high HIV-1 RNA group,the high HIV-1 DNA group,and the low CD4 +T cell group(U=3.00, 0.50 and 3.00,P<0.05 or <0.01).In addition, rs368234815 was associated with IL-21 level(H=6.690,P<0.05),the IL-21 level in rs368234815 ΔG/ΔG [131.88(2.66,174.00)]was higher than that in TT/TT[6.79(2.81,26.48)](P<0.05);rs4803223 was correlated with IFN-γlevel(H=6.690, P<0.05),the IFN-γlevel in GG subtype[62.26(19.45, 96.49)]was higher than that in GA subtype[6.98(2.19, 99.14)](P<0.05).Conclusion The polymorphisms of IFNL3/IFNL4 rs368234815, rs8099917 and rs4803223 are associated with efficacy of HAART and immune-associated cytokines levels in patients with HIV-1 infection.

摘要： [目的]分析高依从性对长期行高效抗反转录病毒治疗(HAART)艾滋病患者临床效果及免疫功能的影响.[方法]根据患者用药依从性将257例接受高效抗反转录病毒治疗的艾滋病患者分为高依从性组与低依从性组,以治疗随访2年为研究终点,比较两组病毒抑制率、治疗前后免疫功能指标及血清炎症因子变化情况.[结果]高依从性组病毒抑制率85.63%显著高于低依从性组的53.33%,差异具有统计学意义(P0.05);高依从性组治疗后上述指标均明显优于低依从性组(P<0.05).[结论]高依从性能明显提高HAART治疗效果,促患者免疫功能重建.

摘要： Objective To investigate the effect of different HAART regimens on liver function,viral load and CD4+T cells of HIV infected children with HCV co-infection.Methods A total of 40 patients were divided into 4 groups:13 cases in AZT+3TC+NVP group(group A),16 cases in AZT+3TC+EFV group(group B),5 cases in D4T+3TC+EFV group(group C)and 6 cases in D4T+3TC+NVP group(group D).Liver function,viral load and CD4+T cells of patients in 4 groups were compared between before and after HAART.Results Eight patients(20％)had abnormal liver function before HAART treatment,and all of them had 1 level of liver damage.After receiving HAART,levels of ALT and AST were increased in group A and B(P0.05).Conclusion Different HAART regimens can increase the liver damage in HIV infected children co-infected with HCV,but have little effect on the treatment efficiency of HAART regimens.%目的 探讨高效抗逆转录病毒治疗(HAART)不同治疗方案对人类免疫缺陷病毒(HIV)合并丙型肝炎病毒(HCV)感染患儿肝功能、HIV载量、CD4+T细胞的影响.方法 40例患者分为齐多夫定(AZT)+拉米夫定(3TC)+奈韦拉平(NVP)联合组13例(A组),AZT+3TC+依非韦伦(EFV)联合组16例(B组),司他夫定(D4T)+3TC+EFV治疗组5例(C组),D4T+3TC+NVP治疗组6例(D组).检测比较4组治疗前后肝功能、HIV载量、CD4+T细胞.结果 HAART治疗前肝功能异常8例(20％),均为1级肝损害.4组治疗后A、B组ALT、AST上升(P0.05).结论 HIV合并HCV感染患儿HAART不同治疗方案可增加肝损害,但对HAART治疗效果影响有限.

摘要： 目的 分析儿童长期抗病毒治疗效果,探索影响儿童抗病毒疗效及生长发育的因素,为提高抗病毒治疗效果提供参考.方法 采用回顾性分析的方法,对2004年至2016年入组抗病毒治疗的艾滋病儿童进行统计学分析,每半年统计身高、体质量、CD4+T淋巴细胞计数,每年统计HIV RNA载量.比较治疗0.05);病毒抑制率分别为92.9%和97.6%,两组比较差异无统计学意义(χ2=1.071,P=0.393);治疗第1年的儿童病毒抑制率为85.7%,治疗10年以上儿童病毒抑制率为100.0%;5例耐药(2例疗程1~5年,3例疗程5~10年),更换了洛匹那韦/利托那韦后病毒得到完全抑制;全部儿童服药依从性均>95.0%.64.8%的儿童达到标准身高,68.5%的儿童达到标准体质量;家庭抚养儿童和社会组织抚养儿童的基线、末次CD4+T淋巴细胞计数比较差异均无统计学意义(Z值分别为-1.159和-0.523,均P>0.05);高收入家庭和低收入家庭的儿童基线和末次CD4+T淋巴细胞计数比较差异均无统计学意义(Z值分别为-0.019和-0.776,均P>0.05).结论 儿童长期抗病毒治疗能有效提升CD4+T淋巴细胞水平、抑制病毒,保证良好的服药依从性,促进生长发育.但仍有约30%儿童身高、体质量低于正常.服药监督员对治疗效果起到关键性作用.大部分儿童家庭经济状况较差.%Objective To analyze the effect of long-term anti-viral treatment in children with acquired immune deficiency syndrome (AIDS) and investigate the factors affecting the treatment efficacy and growth and development of the children, so as to provide reference for improving the efficacy of antiviral drugs.Methods Children with AIDS receiving anti-retroviral treatment during 2004 to 2016 were retrospectively enrolled.The height, weight and CD4+ T cell counts were recorded every half year and the measurement of HIV RNA load was recorded on an annual basis.The CD4+ T cell counts and viral inhibition rates for the children who were under the treatment in the first year, 1~0.05);and viral inhibition rates were 92.9% and 97.6%, respectively with no statistical significance (χ2=1.071, P>0.05).The viral inhibition rate for the children receiving the treatment for 1 year was 85.7%, while that for whose treatment lasted for more than 10 years was 100.0%.A total of 5 cases developed drug-resistance (2 cases treated for 1 to 5 years and 3 cases for 5 to 10 years), and the virus replication was completely inhibited after switching to Lopinavir/ritonavir (LPV/r).The drug compliance was more than 95.0%.64.8% of children met the standard height, while 68.5% met the standard body mass.The baseline and last measured CD4+ T cell counts showed no significant differences between family-raised and social organization-raised children (Z=-1.159 and -0.523, respectively, both P>0.05).The children from high-income families had no significant differences compared with those from low-income ones in terms of the baseline and last measured CD4+ T cell counts (Z=-0.019 and -0.776, respectively, both P>0.05).Conclusions The long-term anti-retroviral treatment can effectively elevate the CD4+ T cell counts, inhibit viral replication and ensure drug compliance, which may promote the growth and development of children.However, approximately 30% children are still lower than the normal standards in terms of height and body mass.The drug-taking observer plays a central role on treatment effect.Most of the children′s family suffer from poor economic conditions.

摘要： 目的 分析云南省文山壮族苗族自治州(文山州)2012—2015年入组抗病毒治疗(ART)的HIV感染者治疗脱失情况及影响因素.方法 选择文山州2012—2015年4354例入组成年人抗病毒治疗者,采集一般人口学信息、治疗基线状况和初始治疗方案,以及各次随访日期及随访状态,观察至2016年6月底.采用历史性队列研究方法对研究对象脱失情况进行描述,采用寿命表法计算治疗后每6个月的累积维持治疗率;采用Cox比例风险回归模型探讨治疗者脱失的影响因素.结果 文山州2012—2015年入组ART者的脱失比例为25.1%(1092/4354),脱失发生率为14.53/100人年.治疗后第6、12、18、24个月末的累积维持治疗率分别为88%、83%、78%、74%.多因素Cox比例风险回归模型分析显示,男性治疗者脱失风险较女性高(HR=1.24,95% CI:1.09~1.41),年龄≥50岁者治疗脱失风险高于年龄<30岁者(HR=1.27,95% CI:1.06~1.53),未婚/离异/丧偶者治疗脱失风险为已婚/同居者的1.30倍(HR:1.30,95% CI:1.14~1.48),静脉吸毒途径感染者治疗脱失风险是异性传播感染者的1.49倍(HR:1.49,95% CI:1.23~1.82),基线CD4+T淋巴细胞计数<350个/μl、≥500个/μl者脱失风险均高于基线CD4+T淋巴细胞计数为350~499个/μl者,HR(95% CI)值分别为1.34(1.13~1.58)、1.36(1.09~1.71),治疗开始年份为2014年、2015年者脱失风险分别是2012年者的1.25倍(HR:1.25,95% CI:1.04~1.50)和1.26倍(HR:1.26,95% CI:1.02~1.55).结论 文山州HIV感染者的ART脱失率有增加趋势,男性、≥50岁、婚姻状况为未婚/离异/丧偶、静脉吸毒途径感染、治疗开始时CD4+T淋巴细胞计数<350个/μl或≥500个/μl者为治疗脱失的高风险人群.%Objective To understand the antiretroviral treatment (ART) discontinuation rate and its influencing factors among HIV infected patients who initiated ART between 2012 and 2015 in Wenshan prefecture,Yunnan province.Methods Demographic characteristics,baseline informations of ART,initial treatment regimens and follow-up status of a total of 4 354 patients who initiated ART from 2012 to 2015 in Wenshan prefecture were collected. A historical cohort study was used to describe the discontinuation incidence rate of ART.Life table was used to estimate cumulative retention rate and Cox proportional hazard model was used to determine the influencing factors of ART discontinuation. Results The percentage and incidence rate of discontinuation were 25.1%(1 092/4 354)and 14.53 per 100 person-years among patients who initiated ART from 2012 to 2015 in Wenshan prefecture.ART retention rates were 88%,83%,78%, 74% at 6thmonth,12thmonth,18thmonth,24thmonth,respectively.The multivariate Cox proportional hazard regression model showed that male patients were at a higher risk of discontinuation(HR=1.24,95% CI:1.09-1.41)than female patients,patients aged≥50 years were at a higher risk of discontinuation(HR=1.27,95% CI:1.06-1.53)than patients aged<30 years,discontinuation hazard among patients who were unmarried or divorced or widowed was 1.30 times (HR:1.30, 95% CI: 1.14-1.48) as patients who were married or cohabitation,discontinuation hazard among patients infected with HIV through injection drug use(IDU)was 1.49 times(HR:1.49,95% CI:1.23-1.82)as those infected through heterosexual transmission,patients with a baseline CD4 cell count<350/μl(HR=1.34,95% CI:1.13-1.58)or≥500/μl(HR=1.36,95% CI:1.09-1.71) were at a higher risk of discontinuation than those with a baseline CD4 cell count from 350/μl to 500/μl, patients initiating ART in 2014 (HR=1.25, 95% CI: 1.04-1.50) or in 2015 (HR=1.26, 95% CI: 1.02-1.55) were at a higher risk of discontinuation than those initiating ART in 2012.Conclusion There is an uptrend for ART discontinuation rate in Wenshan prefecture. Male, 50 years or older, unmarried or divorced or widowed, transmission route as IDU, baseline CD4 count <350/μl or ≥500/μl are risk factors of ART discontinuation.

摘要： 本发明涉及用于鉴定人类免疫缺陷型病毒(HIV)感染和获得性免疫缺陷综合症(AIDS)的药物治疗方案的有效性的抗病毒药物敏感和抗性测试，本发明还涉及检测HIV感染的临床进程及其对抗逆转录病毒治疗，特别是使用表型敏感性测试或基因型测试的核苷类逆转录酶抑制剂治疗的响应的手段和方法。

摘要： 本发明涉及用于检测治疗人类免疫缺陷型病毒(HIV)感染和获得性免疫缺陷综合症(AIDS)的药物有效性的抗病毒药物敏感性和抗性测试，本发明还涉及监测HIV感染的临床进程以及对抗逆转录病毒疗法，特别是使用表型敏感性测试或基因型测试的非核苷逆转录酶抑制剂疗法的响应。

摘要： 本发明涉及从螺旋藻中提取的新的硫脂、获得所述硫脂的方法、含有所述硫脂的组合物及其作为HIV-1和HIV-2的抑制物的用途。本发明还涉及富含具有抑制HIV-1和HIV-2逆转录酶活性的硫脂的螺旋藻生物体，以及所述硫脂或富含所述硫脂的螺旋藻生物体在制备预防或治疗AIDS的药物中的用途。

摘要： 本发明涉及用于鉴定人类免疫缺陷型病毒(HIV)感染和获得性免疫缺陷综合症(AIDS)的药物治疗方案的有效性的抗病毒药物敏感和抗性测试,本发明还涉及检测HIV感染的临床进程及其对抗逆转录病毒治疗,特别是使用表型敏感性测试或基因型测试的核苷类逆转录酶抑制剂治疗的响应的手段和方法。

摘要： 本发明方法包括用带人体免疫缺陷病毒I型(HIV-1)gag和蛋白酶基因的重组疫苗病毒和带有HIV-2env基因的重组疫苗病毒共同感染哺乳动物宿主细胞，制备非复制性重组制备的HIV-1颗粒。这些与天然HIV-1具有非常接近的免疫学和形态学特征的非复制性重组制备的HIV-1颗粒能在体外阻止活的HIV的感染，在体内具有高度的致免疫性。重组制备的HIV-1颗粒可用作抗病毒剂和疫苗制品中的免疫原，有效地抑制或预防HIV的感染和/或获得性免疫缺陷综合症的发展。

摘要： 本发明涉及用于检测治疗人类免疫缺陷型病毒(HIV)感染和获得性免疫缺陷综合症(AIDS)的药物有效性的抗病毒药物敏感性和抗性测试，本发明还涉及监测HIV感染的临床进程以及对抗逆转录病毒疗法，特别是使用表型敏感性测试或基因型测试的非核苷逆转录酶抑制剂疗法的响应。

摘要： 本发明涉及用于检测治疗人类免疫缺陷型病毒(HIV)感染和获得性免疫缺陷综合症(AIDS)的药物有效性的抗病毒药物敏感性和抗性测试,本发明还涉及监测HIV感染的临床进程以及对抗逆转录病毒疗法,特别是使用表型敏感性测试或基因型测试的非核苷逆转录酶抑制剂疗法的响应。

摘要： 本发明涉及从螺旋藻中提取的新的硫脂、获得所述硫脂的方法、含有所述硫脂的组合物及其作为HIV－1和HIV－2的抑制物的用途。本发明还涉及富含具有抑制HIV－1和HIV－2逆转录酶活性的硫脂的螺旋藻生物体，以及所述硫脂或富含所述硫脂的螺旋藻生物体在制备预防或治疗AIDS的药物中的用途。

摘要： 本发明公开一种逆转录病毒原病毒序列在逆转录病毒疫苗设计中的应用，针对特定个体或特定人群感染的原病毒序列，设计亚单位疫苗、灭活疫苗、减活疫苗、重组疫苗和核酸疫苗等。能够直接激活人体免疫系统产生特异性抗患者所携带逆转录病毒的抗体，既回避了流行中逆转录病毒病毒株耐药的痼疾，又特异性靶向患者所携带逆转录病毒毒株。由于逆转录病毒感染者所携带的原病毒序列是整合入人体基因组的DNA序列，它相较于其他感染形式中的RNA序列具有高度保守性，故据此应用设计开发的疫苗具有更强的特异性，是克服目前逆转录病毒疫苗研发瓶颈的一个候选者，具有更好的应用前景。

摘要： 在治疗HIV中，在采用高效抗逆转录病毒治疗(HAART)方法治疗HIV的适当时期施用双链RNA，可通过延长停止HAART后与HIV反弹前之间的时间而允许中断HAART治疗。