切换至 "中华医学电子期刊资源库"

中华实验和临床感染病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (04) : 330 -334. doi: 10.3877/cma.j.issn.1674-1358.2017.04.004

临床论著

河南省某县获得性免疫缺陷综合征患者二线抗病毒疗效及耐药变异分析
尚明全1, 张旻2, 尚红2,()   
  1. 1. 110001 沈阳市,中国医科大学附属第一医院检验科卫计委艾滋病免疫学重点实验室;024000 赤峰市,内蒙赤峰市医院检验科
    2. 110001 沈阳市,中国医科大学附属第一医院检验科卫计委艾滋病免疫学重点实验室
  • 收稿日期:2016-10-10 出版日期:2017-08-15
  • 通信作者: 尚红
  • 基金资助:
    国家科技重大专项资助(No. 2008ZX10102)

Effect and drug resistance variation of second-line antiretroviral therapy among patients with acquired immune deficiency syndrome in a county of Henan Province

Mingquan Shang1, Min Zhang2, Hong Shang2,()   

  1. 1. Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110001, China; Clinical Laboratory, Chifeng Municipal Hospital, Chifeng 024000, China.
    2. Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
  • Received:2016-10-10 Published:2017-08-15
  • Corresponding author: Hong Shang
引用本文:

尚明全, 张旻, 尚红. 河南省某县获得性免疫缺陷综合征患者二线抗病毒疗效及耐药变异分析[J/OL]. 中华实验和临床感染病杂志(电子版), 2017, 11(04): 330-334.

Mingquan Shang, Min Zhang, Hong Shang. Effect and drug resistance variation of second-line antiretroviral therapy among patients with acquired immune deficiency syndrome in a county of Henan Province[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2017, 11(04): 330-334.

目的

了解我国河南省尉氏县部分获得性免疫缺陷综合征(AIDS)患者在更换二线抗病毒治疗方案后的疗效及耐药情况,并分析可能影响二线方案疗效的相关因素。

方法

对65例AIDS患者在换药前、二线方案治疗6个月、治疗12个月时分别进行随访调查,并分别行CD4+ T细胞、病毒载量及耐药情况检测。

结果

队列中65例AIDS患者,经二线方案治疗12个月后,CD4+ T细胞的均值与基线相比显著升高(t =-2.417、P = 0.017),病毒载量均值显著降低(t = 2.343、P = 0.021),病毒载量< 400拷贝/ml患者由换药前的6.2%上升至62.3%(χ2 = 42.704、P < 0.001)。换药前患者交叉耐药和多药耐药严重,二线方案治疗12个月后,检出耐药患者比例由换药前78.5%(51/65)下降为11.3%(6/53);更换二线方案治疗前后均未检测到蛋白酶抑制剂(PI)耐药患者。换药前患者CD4+ T < 100个/μl和HIV-1 RNA> 10 000拷贝/ml与治疗后病毒载量未能有效抑制相关(OR = 5.14,95%CI:0.99~26.71;OR = 3.36,95%CI:0.66~17.21)。

结论

二线抗病毒方案疗效显著。更换二线方案前后均未发现PI耐药,但检出大量蛋白酶抑制剂次要变异,应对更换二线抗病毒治疗方案患者进行长期的耐药监测。

Objective

To investigate the efficacy and drug resistance of patients with acquired immune deficiency syndrome (AIDS) in Weishi County of Henan province after the change of second-line antiviral therapy, and to analyze the factors which affect the efficacy of second-line therapy.

Methods

Total of 65 patients with AIDS were followed up before treatment change, 6 months and 12 months after second-line antiviral therapy. The CD4+ T cell counts, viral load and genotypic resistance testing were detected, respectively.

Results

Among the cohort of 65 patients with AIDS, treatment for 12 months after the second-line, the mean CD4+ T cell significantly increased compared with the baseline (t =-2.417, P = 0.017), the mean viral load decreased significantly (t = 2.343, P = 0.021), and patients of viral load < 400 copies/ml increased from 6.2% to 62.3% (χ2 = 42.704, P < 0.001). Cross resistance and multi-drug resistance were severe in patients with baseline. After 12 months of second-line treatment, the proportion of resistant patients was decreased from 78.5% (51/65) to 11.3% (6/53); protease inhibitor (PI) resistant patients weren’t detected before and after treatment with second-line regimens. Before the change of dressing, patients with CD4+ T < 100 cells/μl and HIV-1 RNA > 10 000 copies/ml were significantly related to virologic failure (OR = 5.14, 95%CI = 0.99-26.71; OR = 3.36, 95%CI = 0.66-17.21).

Conclusions

The second-line antiretroviral therapy was effective. PI drug resistance wasn’t found before and after the second-line regimens was replaced. However, a large number of minor protease inhibitors mutations were detected. Long-term resistance surveillance should be carried out in patients with second-line antiretroviral therapy.

图1 标本与Maker位置比较图
表1 65例研究对象换药前的基本临床资料
图2 入组65例患者CD4+ T细胞计数均值
图3 入组65例患者的病毒载量
表2 二线方案治疗后65例患者CD4+ T细胞计数和病毒载量
表3 Logistic回归分析53例患者经二线方案治疗12个月后未到达病毒学抑制相关因素
[1]
Yeni P. Update on HAART in HIV[J]. J Hepatol,2006,44(Suppl 1):S100-S103.
[2]
Zhou J, Paton NI, Ditangco R, et al. Experience with the use of a first line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database[J]. HIV Med,2007,8(1):8-16.
[3]
Koigi P, Ngayo MO, Khamadi S, et al. HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya[J]. BMC Res Notes,2014,9(7):890-896.
[4]
Katusiime C, Ocama P, Kambugu A. Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review[J]. Afr Health Sci, 2014,14(3):679-681.
[5]
王艳, 邢辉, 王哲, 等. 河南省某县HIV感染者耐药性影响因素分析[J]. 中国公共卫生,2007,23(7):803-805.
[6]
Zhang M, Han XX, Cui WG, et al. The impacts of current antiretroviral therapy regimens on Chinese AIDS patients and their implications for HIV-1 drug resistance mutation[J]. Jpn J Infect Dis,2008,61(5):361-365.
[7]
World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006 revision[S]. Geneva Switzerland WHO Department of HIV. 2006.
[8]
Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel[J]. JAMA,2000,283(3):381-390.
[9]
Thompson MA, Aberg JA, Cahn P, et al. Anti-retroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel[J]. JAMA,2010,304(3):321-333.
[10]
Wang J, Wang Z, Liu J, et al. Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China[J]. Sci Rep,2015,5:14823.
[11]
Hosseinipour MC, Kumwenda JJ, Weigel R, et al. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline[J]. HIV Med,2010,11(8):510-518.
[12]
Han Y, Li Y, Xie J, et al. Week 120 efficacy of tenofovir, lamivudine and lopinavir/r-based second-line antiretroviral therapy in treatment-experienced HIV patients[J]. PLoS One,2015,10(3):e0120705.
[13]
Pujades-Rodríguez M, Balkan S, Arnould L, et al. Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries[J]. JAMA,2010,304(3):303-312.
[14]
Chakravarty J, Sundar S, Chourasia A, et al. Outcome of patients on second line antiretroviral therapy under programmatic condition in India[J]. BMC Infect Dis,2015,15(1):517-528.
[15]
Kušić J, Mladenović M, Dimitrijević B, et al. Treatment outcomes of first-line antiretroviral therapy in HIV-1-positive patients in Serbia[J]. J Virus Erad,2016,2(1):32-35.
[16]
Hosseinipour MC, Gupta RK, Van Zyl G, et al. Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings[J]. J Infect Dis,2013,207(Suppl 2):S49-S56.
[17]
Johnston V, Cohen K, Wiesner L, et al. Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch[J]. J Infect Dis,2014,209(5):711-720.
[18]
Chkhartishvili N, Sharvadze L, Dvali N, et al. Virologic outcomes of second-line antiretroviral therapy in Eastern European country of Georgia[J]. AIDS Res Ther,2014,11(1):18-24.
[19]
Mocroft A, Phillips AN, Miller V, et al. The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study[J]. AIDS,2001,15(2):201-209.
[20]
Kempf DJ, King MS, Bernstein B, et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine[J]. J Infect Dis,2004,189(1):51-60.
[21]
Bongiovanni M, Bini T, Adorni F, et al. Virological success of lopinavir/ritonavir salvage regimen is affected by an increasing number of lopinavir/ritonavir-related mutations[J]. Antivir Ther,2003,8(3):209-214.
[22]
Pujades-Rodríguez M, O’Brien D, Humblet P, et al. Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières[J]. AIDS,2008,22(11):1305-1312.
[23]
Thao VP, Quang VM, Wolbers M, et al. Second-line HIV therapy outcomes and determinants of mortality at the largest HIV referral center in Southern Vietnam[J]. Medicine (Baltimore),2015,94(43):e1715.
[24]
Zhang M, Shang M, Yang W, et al. Treatment effect and drug-resistant mutations in Chinese AIDS patients switching to second-line antiretroviral therapy[J]. PLoS One,2014,9(10):e110259.
[1] 丁科, 张亚琼, 刘杰, 邓莉平, 张永喜, 熊勇. 获得性免疫缺陷综合征相关淋巴瘤患者的临床特征及生存状况的变化趋势[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(05): 278-284.
[2] 吴令杰, 陈瑞烈, 肖湘明, 郭耿龙, 林钟滨, 张海生, 周敏, 陈妙华. 2005至2021年广东省汕头市某综合医院人类免疫缺陷病毒感染/获得性免疫缺陷综合征患者流行病学特征及高效抗逆转录病毒治疗后生存状况影响因素[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(04): 207-214.
[3] 朱琳, 陈韬, 张慎, 许东. 华中地区某三甲医院感染科近十年病原菌结构及耐药性变迁[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(02): 75-82.
[4] 陈浩, 王萌. 胃印戒细胞癌的临床病理特征及治疗选择的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 108-111.
[5] 邢嘉翌, 龚佳晟, 祝佳佳, 陆群. 肺癌化疗患者继发肺部感染的病原菌耐药性及炎症因子变化分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 714-718.
[6] 杨慧, 郭丽娟, 冯晓丹, 李静, 黄成谋, 蔡兴锐, 覃英娇, 王远礼. 非小细胞肺癌铂类药物耐药mi RNA表达特征及预测分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 719-724.
[7] 刘春军, 严方方, 王宝锋, 常婷婷, 郭红红, 李志强. 替加环素联合人免疫球蛋白治疗XDRAB致VAP 的疗效分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 797-800.
[8] 王蕊, 林先萍, 李盼盼. 铜绿假单胞菌感染肺炎菌血症危险因素及耐药性分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 478-480.
[9] 殷国青, 曾莉, 贺斌峰, 孙芬芬. Rab26负性调控Nrf2增强肺癌耐药细胞对奥希替尼的敏感性[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 349-355.
[10] 王向前, 李清峰, 陈磊, 丘文丹, 姚志成, 李熠, 吴荣焕. 姜黄素抑制肝细胞癌索拉非尼耐药作用及其调控机制[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 729-735.
[11] 王涛, 刘静, 高玉伟, 王兴华, 胡秀红, 崔红蕊, 徐保振, 杨洪娟. 抗生素耐药背景下中医药防治腹膜透析相关性腹膜炎研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(06): 340-344.
[12] 徐靖亭, 孔璐. PARP抑制剂治疗卵巢癌的耐药机制及应对策略[J/OL]. 中华临床医师杂志(电子版), 2024, 18(06): 584-588.
[13] 虞岱瑶, 冯文莉. 不同状态下SAP2和STP1在白念珠菌伊曲康唑耐药中的作用[J/OL]. 中华临床医师杂志(电子版), 2024, 18(03): 283-294.
[14] 陈怡丽, 刘平娟, 郭鹏豪, 邓间开, 彭雅琴, 伍众文, 刘敏, 陈培松, 廖康. 全国细菌耐药监测网实践培训基地教学质量评价体系的建立与实践[J/OL]. 中华临床实验室管理电子杂志, 2024, 12(03): 155-161.
[15] 李佳佳, 李凌华, 吕诗韵, 冯凯, 刘琳珊, 钟海丹, 颜婵, 刘聪. 广州市病毒学抑制失败HIV/AIDS患者的耐药特征及影响因素分析[J/OL]. 中华卫生应急电子杂志, 2024, 10(04): 207-212.
阅读次数
全文


摘要