吸毒成瘾HIV/AIDS患者抗逆转录病毒治疗的初步探讨

目的 评价国产艾滋病抗病毒药物治疗吸毒成瘾艾滋病病毒感染者/病人(HIV/AIDS)的疗效及对治疗时机的探讨. 方法 采用回顾性研究方法,调查随访2004～2007年在北京佑安医院确诊并经抗病毒治疗的吸毒成瘾HIV/AIDS患者114例,按照疾病进展将随访对象分成艾滋病组( AIDS)和HIV感染组(free of AIDS) ,所有患者均用3种抗病毒药物(奈韦拉平 司他夫定 拉米夫定)治疗,疗程48周.常规方法检测患者治疗前后血CD4 T淋巴细胞数,核酸序列扩增技术(NASBA)测定病毒载量. 结果 114例吸毒成瘾HIV/AIDS患者CD4细胞数平均增加(182.39±90.70)个/mm3;其中35例吸毒成瘾HIV/AIDS患者中85.71%病毒载量下降至50 copies/ml以下, 下降2.5个Log数;艾滋病组与HIV感染组治疗后3、6、9和12个月CD4 T淋巴细胞差异有统计学意义(P＜0.05);治疗6个月后,HIV感染组病毒载量下降趋势较艾滋病组明显,但治疗12个月后 HIV感染组病毒载量较艾滋病组有反弹现象. 结论 吸毒成瘾HIV/AIDS患者选用国产艾滋病抗病毒药物奈韦拉平 司他夫定 拉米夫定治疗取得良好效果,并且对艾滋病患者的疗效好于HIV感染者.     

32例HIV/AIDS患者HAART治疗效果

目的为了了解高效抗逆转录病毒治疗(HAART)有效组合,减轻药物的毒副作用,增强疗效,改善艾滋病(AIDS)患者和艾滋病病毒(HIV)感染者生存质量。方法对32例AIDS/HIV患者,采用国产HAART:奈韦拉平(NVP) 司它夫丁(D4T) 去羟肌苷散(DDI)常规服药,治疗观察时间6个月。结果30例CD4计数平均增加130±130.38个/μl;CD4/CD8比值平均增加0.207±0.104,2例(57岁、62岁各1例)治疗1~2个月后因肺部感染而死亡。提示HAART能够有效促进免疫重建,减轻症状,延长生命;但治疗开始时间与HIV感染的时间、年龄、CD4细胞和CD4/CD8比值有明显的相关性。结论治疗要抓住有利时机,尽可能早治疗,促进和加快免疫重建。尤其对儿童与老年人更应选择有利时机早治疗。     

奈韦拉平引起严重过敏3例分析

随着新疆免费艾滋病抗病毒药物治疗的开展, 由艾滋病抗病毒药物引起的不良反应也正逐渐增多.新疆疾病预防控制中心附属传染病院自2004年8月开始使用拉米夫定(3TC,葛兰素威康公司)、齐多夫定片(AZT,东北制药总厂)、奈韦拉平片(NVP, 上海迪赛诺公司)和司他夫定胶囊(d4T, 上海迪赛诺公司)、拉米夫定、奈韦拉平片这两种方案联合治疗艾滋病患者,其中有 3 例患者在接受治疗时发生了由奈韦拉平片引起的药疹, 现报告如下.     

拉米夫定治疗艾滋病致全身过敏性皮疹一例

1临床资料某女,30岁,已婚,汉族。既往无药物过敏史。2008年1月28日在玉溪市疾病预防控制中心确诊艾滋病病毒(Human immunodeficiency virus,HIV)抗体阳性。2008年6月27日CD4T细胞342个/μL,在玉溪市人民医院感染科门诊服用司他夫定、拉米夫定、奈韦拉平抗病毒治疗1个月。检查肝功能结果显示:TBIL     

去羟肌苷、司他夫定联合奈韦拉平治疗艾滋病患者临床观察

目的观察2核苷类逆转录酶抑制剂(NRTI)联合1非核苷类逆转录酶抑制剂(NNR-TI)抗逆转录病毒方法治疗艾滋病的效果和不良反应。方法用去羟肌苷(ddI)、司他夫定(d4T)联合奈韦拉平(NVP)治疗20例HIV-1感染者和艾滋病患者(HIV/AIDS),将其分为A组(进口药)、B组(国产药)并进行为期1年的观察。随访指标为病毒载量、T淋巴细胞计数和不良反应。结果治疗1年,A组中2例因严重不良反应而终止。治疗1个月后两组的血浆病毒载量平均值明显下降,A组比治疗前下降2.12lg拷贝/ml,B组比治疗前下降2.55lg拷贝/ml。A、B两组分别在4.3个月和2个月时,均检测不到病毒载量。CD4细胞计数和CD4/CD8比例逐渐升高,由治疗前A组(231.50±156.02)/mm3、0.25±0.21,B组(49.60±45.41)/mm3、0.07±0.05,上升至治疗后A组(423.70±225.79)/mm3、0.46±0.31,B组(186.00±92.47)/mm3、0.20±0.11。两组比较,治疗前后的血浆HIVRNA降幅、CD4细胞计数和CD4/CD8比例增幅无统计学意义。治疗前CD4>200/mm3者,治疗后CD4细胞计数和CD4/CD8比例升高的绝对值明显高于CD4<200/mm3者。治疗初期不良反应有胃肠道反应、中枢神经系统症状和皮疹,不需治疗可自行缓解,严重的不良反应是周围神经病变。结论该药物组合能够很快地使病毒载量水平明显降低,同时也能够使大多数患者的免疫功能得以重建。严重的不良反应表现有周围神经病变。     

艾滋病合并布鲁菌病一例

患者男,33岁.因发现抗-HIV阳性4年余,头痛1个月,发热2周入院.患者4年前体检发现抗-HIV阳性时CD4~+T淋巴细胞为269×10~6/L,开始司他夫定+拉米夫定+奈韦拉平抗病毒治疗.复查CD4~+T淋巴细胞最高达572×10~6/L.1个月前无明显诱因头痛,为枕部及顶部持续性疼痛,曾呕吐胃内容物1次,非喷射性.2周前无诱因出现发热,体温38.0～39.5℃,无明显规律.     

《中华传染病杂志》2006年第24卷作者索引

本索引仅收录第一作者姓名.并按汉语拼音字母顺序排列。安萍乙型肝炎病毒携带者肝组织T淋巴细胞CD28的表达(2):99白雪帆第七次全国肾综合征出血热学术会议纪要(5): 359蔡皓东阿德福韦治疗失代偿期慢性乙型肝炎九例(6): 4 13蔡卫平去经肌昔、司他夫定联合奈韦拉平治疗艾滋病患者临床观察(1):39陈瑞耐亚胺培南铜绿假单胞菌外膜蛋白D基因突变检测(2):80陈公英浙江省乙型肝炎病毒B、C基因型感染者临床和肝组织病理的比较(2): 113陈光远雷州半岛地区44例类鼻疽病的临床特征分析(6):4()6陈凯红甘草酸二钱治疗慢性乙型肝炎患者的细胞免疫功能变…     

WHO实施"3乘5"计划开发抗AIDS新药

2003年12月1日，世界卫生组织(WHO)和联合国艾滋病规划署(UNAIDS)实施“3乘5”计划，到2005年治疗3百万艾滋病(AIDS)患者，此前在AIDS高发区所采取的一些措施已初见成效。最近WHO认可三种常规药物作为抗AIDS首选药，均已达到WHO所要求的质量、安全和高效的标准。这些治疗AIDS的药是包含拉米呋啶、司他呋啶和奈韦拉平成分的三联药，相对低廉的成本，使更多的AIDS患者支付得起药费，及时得到有效的治疗，增大患者治愈的机会。     

18例抗病毒治疗失败儿童艾滋病患者耐药基因突变规律研究

目的对儿童艾滋病抗病毒治疗失败病例的耐药基因突变规律及特点进行研究。方法分析18例接受过高效抗逆转录病毒治疗并已经出现病毒学及免疫学失败儿童艾滋病患者的横断面临床及实验室资料,对其耐药突变结果进行分析。结果患者年龄11.6±2.4岁,治疗的时间为36±12个月,其中15例患者曾经接受过成人抗病毒药物治疗,患者的 CD4~ T 淋巴细胞为34±30个/μl(3～96个/μl),病毒载量为5.23±0.57 log10 copies/ml(4.27～6.53 log10 copies/ml)。耐药发生率为100%。对非核苷类逆转录酶抑制剂(NNRTIs)耐药突变结果分析显示:所有患者均对奈韦拉平(NVP)产生高度耐药,对依非韦伦(EFV)高度耐药的有16例。对核苷类逆转录酶抑制剂(NRTIs)耐药突变结果分析显示:对拉米夫定(LAM)高度耐药的有14例,对去羟肌苷(ddI)高度耐药的有11例,对齐多夫定(AZT)高度耐药的有14例,对司他夫定(d4T)高度耐药的有16例。重要突变位点包括 Y181C(9例)、K103N(7例)、G190A(8例)、TAMs(17例)、M184V(10例)、K65R(5例)、Q151M(2例)。结论该组治疗失败儿童患者对正在使用的 NRTIs 及 NNRTIs 均已产生高度耐药,须考虑更换新的抗病毒治疗方案。     

中国成人HIV/AIDS病人抗病毒治疗失访情况及其影响因素分析

目的了解中国成人艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)抗病毒治疗失访比例及其影响因素。方法对全国免费抗病毒治疗库中,2012年1月1日至12月31日开始抗病毒治疗的HIV/AIDS病人失访情况进行随访,随访截止到2014年12月31日。采用Cox比例风险模型分析队列失访率及其影响因素。结果共有26 742名HIV感染者进入队列。12个月的累积失访率为7.6/100人年,24个月的累积失访率为10.5/100人年。Cox比例风险模型多因素分析显示,基线高CD4+T淋巴细胞组、注射吸毒、异性性传播以及初始治疗方案为齐多夫定/司坦夫定+拉米夫定+依非韦伦/奈韦拉平与较高的失访率相关(P0.05)。结论应该重点强化注射吸毒HIV/AIDS病人的干预措施,加强对高基线CD4+T淋巴细胞HIV/AIDS病人感染者的医疗咨询,对治疗药物有不良反应的病人要及时处理或更换治疗方案。     

Comparison of twice-daily stavudine plus once- or twice-daily didanosine and nevirapine in early stages of HIV infection: the scan study

OBJECTIVES: To evaluate the safety and effectiveness of once-daily didanosine and nevirapine plus twice-daily stavudine versus twice-daily administration of all three drugs. METHODS: This open-label, randomized, multicentre study enrolled 94 antiretroviral-naive patients with chronic HIV infection, CD4+ cell counts > 500 x 10(6) cells/l, and viral loads > 5000 copies/ml. Patients were treated with either 40 mg stavudine (twice daily) plus 400 mg didanosine (once daily) and 400 mg nevirapine (once daily) or 40 mg stavudine (twice daily) plus 200 mg didanosine (twice daily) and 200 mg nevirapine (twice daily). RESULTS: After 12 months, 68% of patients who received twice-daily didanosine and nevirapine had viral loads < 200 copies/ml in the intention-to-treat and 79% in the on-treatment analysis, respectively. The corresponding values for patients treated with didanosine and nevirapine, taken once-daily, were 73 and 85%. The percentages of patients in each group with viral loads < 5 copies/ml at 12 months were 40% (once daily ) and 45% (twice daily) for the intention-to-treat analysis. Five of 11 patients (45%) with plasma viral loads < 5 copies/ml at 12 months had detectable virus in tonsillar tissue. Genotypic resistance to nevirapine was noted in seven of the 14 patients with detectable viral load at month 12. Mean changes in CD4+ cell counts for patients treated with stavudine plus once- or twice-daily didanosine and nevirapine were 154 and 132 x 10(6) cells/l, respectively. Treatment was interrupted due to adverse events in seven patients (8%) (four who received once-daily didanosine and nevirapine and three treated with twice-daily doses). CONCLUSIONS: The combination of twice-daily stavudine plus once-daily didanosine and nevirapine was as safe and well tolerated as twice-daily administration of all three agents. Both regimens were equally effective in reducing viral loads and in increasing CD4+ cell counts.     

The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus.

A total of 151 previously untreated patients infected with human immunodeficiency virus type 1 (HIV-1) with CD4 cell counts >/=200/microL and plasma HIV-1 RNA levels of 10,000-100,000 copies/mL were randomly assigned to 24 weeks of open-labeled stavudine plus didanosine (group 1), zidovudine plus lamivudine (group 2), or stavudine plus didanosine followed by zidovudine plus lamivudine (group 3). The mean decrease in HIV-1 RNA level was greater in group 1 (2.26 log10 copies/mL) than in groups 2 (1.26 log10 copies/mL) or 3 (1.58 log10 copies/mL; P<.0001). The mean increase in CD4 cell counts was greater in groups 1 (124 cells/microL) and 3 (118 cells/microL) than in group 2 (62 cells/microL; P=.02). All regimens were generally well tolerated. The combination of stavudine plus didanosine reduced plasma HIV-1 RNA concentrations and increased CD4 cell counts more effectively than did the combination of zidovudine plus lamivudine or the regimen alternating both combinations.     

High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals.

OBJECTIVE: To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with nevirapine, zidovudine and didanosine in 51 antiretroviral-naive HIV-1-infected patients. The relationships between the value of k, the time to reach an undetectable HIV-1 RNA concentration in plasma (< 20 copies/ml) and the success of therapy after 52 weeks of treatment as dependent variables and the exposure to nevirapine, baseline HIV-1 RNA and baseline CD4 cell count as independent variables, were explored using linear regression analyses, proportional hazard models and logistic analyses, respectively. RESULTS: The value of k for HIV-1 RNA in plasma was positively and significantly associated with the mean plasma nevirapine concentration during the first 2 weeks of therapy (P = 0.011) and the baseline HIV-1 RNA (P = 0.008). Patients with a higher exposure to nevirapine reached undetectable levels of HIV-1 RNA in plasma more rapidly (P = 0.03). From 12 weeks on, the median nevirapine plasma concentration was significantly correlated with success of therapy after 52 weeks (P < 0.02). CONCLUSIONS: A high exposure to nevirapine (in a twice daily regimen) is significantly associated with improved virological response in the short as well as in the long term. These findings suggest that optimization of nevirapine concentration might be used as a tool to improve virological outcome in (antiretroviral-naive) patients treated with nevirapine.     

A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients

OBJECTIVE: To compare one protease inhibitor (PI)-based and two PI-sparing antiretroviral therapy regimens. METHODS: International, open label, randomized study of antiretroviral drug-naive patients, with CD4 lymphocyte counts >/= 200 x 106 cells/l and plasma HIV-1 RNA levels > 500 copies/ml. Treatment assignment to stavudine and didanosine plus indinavir or nevirapine or lamivudine. Primary study endpoint was the percentage of patients with plasma HIV-1 RNA levels < 500 copies/ml after 48 weeks in the intention-to-treat analysis (ITT). RESULTS: In total, 298 patients were enrolled. After 48 weeks, the percentage of patients in the indinavir, nevirapine and lamivudine arms with HIV-1 RNA < 500 copies/ml was 57.0%, 58.4% and 58.7%, respectively, in an ITT analysis. After 96 weeks of follow-up, these percentages were 50.0%, 59.6% and 45.0%, respectively. The percentage of patients with HIV-1 RNA < 50 copies/ml was significantly less for those allocated to lamivudine in an on-treatment analysis after 48 and 96 weeks of follow-up. Patients in the nevirapine arm experienced a smaller increase in the absolute number of CD4 T lymphocytes. There were no significant differences in the incidence of serious adverse events. CONCLUSIONS: A comparable virological response can be achieved with first-line PI-base and PI-sparing regimens. The triple nucleoside regimen utilized may be less likely to result in viral suppression to < 50 copies/ml, while the nevirapine-based regimen is associated with a lower increase in CD4 T lymphocytes.     

Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine. AI454-143 Team.

OBJECTIVE: To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). DESIGN: Randomized, double-blind, multicenter study. SETTING: Twenty-one sites in the United States. PATIENTS: Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of > or = 10,000 copies/ml and CD4 cell counts of > or = 100 cells/mm3 started study therapy. INTERVENTIONS: Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. RESULTS: At week 12, median log10 HIV-1 RNA changes were -1.83 log10 copies/ml in the once-daily ddI/d4T group and -1.80 log10 copies/ml in the twice-daily ddI/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). CONCLUSION: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.     

A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II)

OBJECTIVE: Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients. DESIGN: Randomized, open-label. SETTING: Fourteen HIV Clinical Research Centers. PATIENTS: Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts > or = 200 x 10(6)/l and plasma HIV-1 RNA levels > or = 10,000 copies/ml. INTERVENTIONS: Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV. MAIN OUTCOME MEASURES: The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and < or = 50 copies/ml and changes in CD4 cell counts were compared. RESULTS: In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were < or = 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10(6)/l cells for the d4T arm and 106 x 10(6)/l cells for the ZDV arm (P= 0.001). The occurrence of serious adverse events was not significantly different between arms. CONCLUSION: The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.     

Residual low-level viral replication could explain discrepancies between viral load and CD4+ cell response in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

We report the evolution of chronic infection with human immunodeficiency virus type 1 (HIV-1) in a patient treated with stavudine plus didanosine, whose CD4+ lymphocyte count progressively decreased, despite a sustained plasma viral load <20 copies/mL. After 12 months of therapy, treatment was switched to zidovudine plus lamivudine plus nelfinavir. CD4+ T cell count decreased from 559 x 10(6)/L at month 0 to 259 x 10(6)/L at month 12. Plasma viral load decreased from 21,665 HIV-1 RNA copies/mL at baseline (month 0) to <20 copies/mL after 1 month of therapy with stavudine plus didanosine, and remained below 20 copies/mL until month 12, but always >5 copies/mL. Viral load in tonsilar tissue at month 12 was 125,000 copies/mg of tissue. After the change to triple-drug therapy, the plasma viral load decreased to 5 copies/mL, the CD4+ T cell count increased to 705 x 10(6)/L, and the viral load in tonsilar tissue decreased to <40 copies/mg of tissue at month 24. A low level of HIV-1 replication could explain the lack of immunologic response in patients with apparent virological response.     

The effect of baseline CD4 cell count and HIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART

BACKGROUND: A substantial number of patients start their first-line antiretroviral therapy at an advanced stage of an HIV-1 infection. Potential differences between specific drug regimens in antiviral efficacy and safety in these patients are of major importance. METHODS: A post-hoc analysis within the randomized controlled 2NN trial comparing efficacy between regimes containing nevirapine (NVP), efavirenz (EFV), or both, in addition to stavudine and lamivudine. Primary outcome: risk of virologic failure in different strata of baseline CD4 T-lymphocyte counts and plasma HIV-1 RNA concentrations (pVL). Virologic failure: never reaching a pVL < 400 copies/ml, or a rebound to two consecutive values > 400 copies/ml. RESULTS: The risk of virologic failure was increased at very low CD4 counts (< 25 x 10(6) cells/l) compared to CD4 counts > 200 x 10(6) cells/l [hazard ratio (HR), 1.28; 95% confidence interval (CI), 0.93-1.77]. The same was seen for a pVL > or = 100,000 copies/ml compared to a lower pVL (HR, 1.20; CI, 0.96-1.50). There were no statistically significant differences between NVP and EFV in risk of virologic failure within any of the CD4 or pVL strata, although EFV performed slightly better in the low CD4 stratum. The incidence of rash in the NVP group was significantly higher in female patients with higher CD4 cell counts, while adverse events in the EFV group were not associated with CD4 cell count. CONCLUSIONS: Initial antiretroviral therapy including NVP or EFV is effective in patients with an advanced HIV-1 infection. A high baseline CD4 cell count is associated with the occurrence of rash in female patients using NVP.