河南某农村接受抗病毒治疗的艾滋病患者HIV-1耐药发生的六年队列分析

Objective To analyze the occurring rules of human immunodeficiency virus (HIV)drug resistance under an unique therapy model among HIV-1 infected individuals on antiretroviral therapy (ART) in rural areas of Henan, China. Methods A cohort of 75 individuals on an ART regimen of zidovudine (ZDV) , dideoxyinosine (ddI) and nevirapine (NVP) was established in March 2003. A total of 12 surveillances were conducted and 788 person-times were studied until 2010. The parameters of CD4 cell count and viral load (VL) were tested in each survey. And genotypic resistance testing was performed in patients with a failure of viral suppression. Survival analysis was used to estimate the occurrence time of resistance. Results The cumulative mortality rate was 16% (12/75) in the cohort. And the cumulative resistance rate was 88% (66/75) from 2004 to 2010. The rate of resistance reached 54. 7% and the probability from susceptibility to drugs developing resistance decreased drastically from 100% to 45. 3% within the first 1 year of initiation. The occurrence time of resistance for half of individuals in the cohort was at 12.0 months(95% CI 8. 6 - 17. 0)after initiation, 25. 1 months(95%C/19.0-33. 3)in those whose VL was less than 4. 0 lgU/ml and 4. 8 months (95% CI 4.1 - 5. 6) at VL ＞ 4. 0 lgU/ml during the first investigation. The individuals with an early occurrence of resistance within 12 months carried high risks for afailure of viral suppression and a decrease of CD4 counts. Conclusion The occurrence of resistance rises with the course of therapy. And the greatest probability for resistance is within the first 1 year of initial therapy. A high level of VL has a significant impact on the development of resistance. Preventing the occurrence of resistance during the initial therapy remains a key goal.     

γ射线终末辐照对同种异体肌腱病毒灭活效果及生物力学性能影响的研究

目的研究γ射线终末辐照灭菌对同种异体肌腱病毒灭活的效果及对肌腱生物力学性能的影响。方法采用细胞培养法,检测γ射线辐照(照射剂量25 kGy)灭活PRV、VSV、PPV、EMCV、HIV-1病毒的效果。取正常供体手部肌腱12根,直径4~5 mm,随机分为实验组(辐照组)和对照组(新鲜不处理),进行病毒滴度检测,MTS力学试验机检测两组极限拉伸载荷。结果经过γ射线辐照可使污染在同种异体肌腱上的病毒滴度下降超过4 Log值,且盲传3代无病毒检出。辐照前后,同种异体肌腱极限拉伸载荷和组织结构差异无统计学意义(P0.05)。结论终末辐照灭菌(照射剂量25 kGy)是同种异体肌腱病毒灭活的有效方法,可避免引入其它化学试剂,且该工艺不会影响肌腱的极限拉伸载荷和组织结构。     

椎基底动脉短暂缺血性眩晕脑干功能损害与经颅多普勒的相关性

目的　探讨椎基底动脉供血不足 (VBI)脑干功能与经颅多普勒 (TCD)的相关性。方法　对 6 8例临床诊断VBI的患者及 30例非VBI患者进行BR ,BAEP和TCD检测。结果　VBI组脑干功能损害 84 6 % ,TCD异常率为 83 1% ,χ2 检验差异无显著意义 ;非VBI组脑干功能损害 8 3% ,TCD异常率为 46 6 % ,χ2 检验差异有显著意义。VBI组脑干功能损害及TCD异常者为 98/136 ,皆正常者为 2 4/136 ,两者占 89 7% ;非VBI皆异常者为 4/6 0 ,皆正常者为 32 /6 0 ,两者占 6 0 %。结论　根据临床表现 ,结合BR ,BAEP及TCD检查结果可提高对VBI的诊断价值 ,而单独的TCD结果不足以作为诊断依据。     

河南某农村接受抗病毒治疗的艾滋病患者HIV-1耐药发生的六年队列分析

Objective To analyze the occurring rules of human immunodeficiency virus (HIV)drug resistance under an unique therapy model among HIV-1 infected individuals on antiretroviral therapy (ART) in rural areas of Henan, China. Methods A cohort of 75 individuals on an ART regimen of zidovudine (ZDV) , dideoxyinosine (ddI) and nevirapine (NVP) was established in March 2003. A total of 12 surveillances were conducted and 788 person-times were studied until 2010. The parameters of CD4 cell count and viral load (VL) were tested in each survey. And genotypic resistance testing was performed in patients with a failure of viral suppression. Survival analysis was used to estimate the occurrence time of resistance. Results The cumulative mortality rate was 16% (12/75) in the cohort. And the cumulative resistance rate was 88% (66/75) from 2004 to 2010. The rate of resistance reached 54. 7% and the probability from susceptibility to drugs developing resistance decreased drastically from 100% to 45. 3% within the first 1 year of initiation. The occurrence time of resistance for half of individuals in the cohort was at 12.0 months(95% CI 8. 6 - 17. 0)after initiation, 25. 1 months(95%C/19.0-33. 3)in those whose VL was less than 4. 0 lgU/ml and 4. 8 months (95% CI 4.1 - 5. 6) at VL ＞ 4. 0 lgU/ml during the first investigation. The individuals with an early occurrence of resistance within 12 months carried high risks for afailure of viral suppression and a decrease of CD4 counts. Conclusion The occurrence of resistance rises with the course of therapy. And the greatest probability for resistance is within the first 1 year of initial therapy. A high level of VL has a significant impact on the development of resistance. Preventing the occurrence of resistance during the initial therapy remains a key goal.     

冰毒对HIV-1在巨噬细胞内复制影响的体外实验研究

目的探讨冰毒对人类免疫缺陷病毒-1型（human immunodeficiency virus 1,HIV-1）在巨噬细胞中复制的作用。方法将巨噬细胞按单纯随机分组原则分为：（1）冰毒＋多巴胺受体D1阻滞剂（SCH23390）处理组,（2）冰毒处理组,（3）SCH23390处理组,（4）病毒对照组。先用浓度为10-5mol／L的SCH23390预处理（1）、（3）组1h,再用10μmol／L的冰毒处理（1）组24h,同时用10～mol／L、10μmol／L及2．5×10-4mol／L的冰毒处理（2）组24h,然后每组加入等量的HIV-1进行感染,于感染的第4、6、8、10d取培养上清,用酶联免疫吸附剂测定（enzymelinked immunosorbnent assay,ELISA）检测培养上清的HIV-1 p24抗原,比较各组之间抗原表达量差异。结果HIV-1感染巨噬细胞第4、6、8、10d,病毒对照组的p24抗原表达量均低于3个不同浓度冰毒处理组（均有P〈0．01）;且各浓度冰毒处理组的p24抗原表达量比对照组增加的倍数,随着感染时间的延长而具有上升的趋势,时间．效应差异有统计学意义（F=155．94,P〈0．001）;而冰毒＋SCH23390处理组、SCH23390处理组分别与病毒对照组HIV-1p24抗原表达比较,差异均无统计学意义（均有P〉0．05）。结论冰毒能够促进HIV-1在巨噬细胞内的复制,并随感染时间的延长呈递增趋势;冰毒促进HIV-1复制的作用可被多巴胺受体D1阻滞剂（SCH23390）阻断。     

静脉注射人免疫球蛋白酸性孵放法灭活艾滋病病毒的效果研究

目的研究静脉注射人免疫球蛋白在生产过程中酸性孵放法灭活艾滋病病毒的效果。方法采用细胞培养法,对含有艾滋病病毒的静脉注射人免疫球蛋酸性孵化法灭活效果进行了实验室检测。结果将含有艾滋病病毒的静脉注射人免疫球蛋白酸度调整为pH4,于21～25℃条件下放置4d,其中艾滋病病毒的滴度(TCID50)由9.50log下降至2.00log以下,下降值达到7.00log以上。相同的样品在pH值7.0条件下放置14d,其中艾滋病病毒滴度仍在3.3log以上;经放置21d,所有样品中艾滋病病毒滴度均在2.0log以下。经过对3批样品重复测定,均未出现细胞病变;经过将样品盲传三代仍未出现细胞病变。结论采用酸性孵放法常温下放置21d,可使静脉注射人免疫球蛋白中艾滋病病毒完全失去活性。     

两种非核苷类逆转录酶抑制剂与已上市药物联合应用的体外抗HIV活性研究

目的：评价两种非核苷类逆转录酶抑制剂（JB25、JB26）与3种已上市药物齐多夫定（AZT）、依非韦仑（EFV）、沙奎那韦（SQV）联合应用的体外抗HIV活性。方法：将10个浓度的JB25、JB26分别与AZT、EFV、SQV的7个浓度组成各种浓度的组合,加入384孔细胞培养板,与HIV-1ⅢB急性感染的MT-2细胞共培养3d,最后利用TZMbl细胞报告基因检测HIV-1的表达,共重复3次。利用MacSynergyⅡ软件对数据进行分析,得到药物相互作用的情况。结果：JB25与AZT、EFV、SQV的平均协同/拮抗容量分别是244.45/-5.05,119.58/-65.93,145.83/-0.32（nmol/L）2%;JB26与AZT、EFV、SQV的平均协同/拮抗容量分别是398.90/0,103.62/-0.49,138.473/-0.27（nmol/L）2%。结论：两种非核苷类逆转录酶抑制剂与3种已上市的药物在体外联合应用,具有协同抗HIV作用,MacSynergyⅡ软件可以全面评价两种药物的联合作用情况。     

HIV感染者CD4/CD8细胞与病毒载量的关系

目的　探讨HIV感染者体内CD4细胞数与病毒载量的关系。方法　对 84人的 2 0 7次血样进行病毒载量的测定 ,对 194人的 491次血样进行CD4/CD8细胞数的检测。CD4/CD8细胞计数采用流式细胞仪的绝对计数法进行检测 ,使用核酸序列测试 (NASBA)方法检测病毒载量。对其中一部分人进行随访 ,采集血样并检测相应指标。结果　HIV感染者体内的CD4细胞数与病毒载量的Log值呈负相关 (r =-0 576,P <0 0 1) ,CD4/CD8比值与病毒载量的Log值呈负相关 (r =-0 544,P <0 0 1)。CD4细胞数较低的感染者 ,CD8细胞数也较低。在HIV感染者体内 ,随着病毒载量的升高 ,CD4细胞数呈下降趋势。结论　病毒载量与CD4有明显的相关关系 ,当病毒载量较低时 ,使用CD4细胞数可以粗略估计血浆中病毒载量的高低。CD4/CD8比值与病毒载量的Log值呈现负相关。当病毒载量较高时 ,HIV感染者体内病毒载量与CD4细胞数的变化趋势相反 ,但不完全同步     

广西壮族自治区133例艾滋病患者抗病毒治疗效果评价

目的了解广西壮族自治区部分艾滋病感染者抗病毒治疗后免疫功能恢复与病毒抑制效果。方法2004年7月至2005年10月在广西南宁与柳州地区招募接受抗病毒治疗时间＞3个月的艾滋病患者133例,并在同一地区选择感染时间接近、尚未接受抗病毒治疗感染者58例作为对照。通过专业问卷,了解抗病毒治疗患者服药依从性;采集患者的EDTA抗凝静脉血,通过CD4~+ T淋巴细胞计数与病毒载量测定,了解免疫重建与病毒抑制情况;通过基因型耐药性检测分析抗病毒治疗人群与未治疗人群中HIV-1耐药性毒株的发生情况。结果在接受抗病毒治疗人群中,约有70．69%患者的CD4~+ T淋巴细胞明显回升,23．28%患者CD4~+ T细胞未有明显变化,6．03%的患者CD4 T细胞计数明显下降;比较治疗与未治疗人群病毒载量水平,接受治疗人群载量对数均值(1．834±0．853)显著低于未治疗人群(3．621±1．121)(P＜0．05),治疗人群中67．91%的患者病毒载量水平低于检测限;治疗人群中耐药性发生率(11．90%)与未治疗组(11．63%)无明显差异。结论广西地区实施的抗病毒治疗对免疫系统重建、体内病毒的抑制具有明显作用;耐药性流行情况在治疗与未治疗人群中无明显差异。     

SARS病毒对温度耐受性的实验研究

为观察SARS病毒在冷藏和自然温度下的稳定性以及灭活SARS病毒的有效温度,将SARS病毒培养的上清液(10~6TCID_(50))分装到10ml离心管中,放置在4℃冰箱、室温(24.5℃)、37℃、56℃和70℃水浴中,间隔一定时间以后取样0.5ml,接种Vero-E6细胞。结果,SARS病毒在冷藏和室温条件下十分稳定,冷藏(4℃)放置10d,滴度只下降大约2个log,室温放置5d,滴度下降大约4个log,仍然保持较高的感染性。加热时SARS病毒的滴度迅速下降,56℃加热30min、70℃加热15min检测不出有活病毒。结论,SARS病毒在冷藏和自然温度下十分稳定,加热是灭活SARS病毒简单有效的方法。