Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa
Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa
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DOI：
10.1086/587109
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发表时间：
2008-05-15
影响因子：
11.8
通讯作者：
Kuritzkes, Daniel R.
中科院分区：
文献类型：
--
作者：
Marconi, Vincent C.;Sunpath, Henry;Kuritzkes, Daniel R.
背景1型人体免疫缺陷病毒（HIV-1）抗药性的出现可能会限制抗逆转录病毒疗法在资源有限环境中的益处。在南非夸祖鲁纳塔尔的患者中评估了首次高效抗逆转录病毒治疗（HAART）失败后耐药的患病率。在夸祖鲁纳塔尔的2家诊所，对首次HAART方案病毒学失败的患者的血浆病毒样本进行基因型耐药性检测。临床和人口统计学数据来自医疗记录。进行回归分析以确定与>= 1个显著耐药突变相关的因素。从2005年1月至2006年8月，共招募了124名经历病毒学失败的抗逆转录病毒治疗成人。主要亚型为HIV-1C。来自83.5%参与者的病毒样本携带>= 1个显著耐药突变。64.3%的参与者存在双重耐药病毒，2.6%的参与者存在三级耐药病毒。最常见的突变是M184 V/I（64.3%的患者）; K103 N存在于51.3%的病毒中，V106 M存在于19.1%的病毒中。胸苷类似物耐药突变率为32.2%，蛋白酶耐药突变率为4.4%。在首次HAART治疗失败的南非患者中检测到抗逆转录病毒药物耐药病毒>80%。耐药模式反映了一线治疗方案中使用的药物和病毒亚型。有必要继续监测耐药模式，以指导二线治疗方案的选择。
Background. Emergence of human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy in resource-limited settings. The prevalence of resistance was assessed among patients from KwaZulu Natal, South Africa, following failure of their first highly active antiretroviral therapy (HAART) regimen.Methods. Genotypic resistance testing was performed on plasma virus samples from patients who experienced virologic failure of their first HAART regimen at 2 clinics in KwaZulu Natal. Clinical and demographic data were obtained from medical records. Regression analysis was performed to determine factors associated with >= 1 significant drug resistance mutation.Results. From January 2005 through August 2006, a total of 124 antiretroviral-treated adults who experienced virologic failure were enrolled. The predominant subtype was HIV-1C. Virus samples from 83.5% of participants carried >= 1 significant drug resistance mutation. Dual-class drug-resistant virus was present in 64.3% of participants, and 2.6% had virus with triple-class drug resistance. The most common mutation was M184V/I (64.3% of patients); K103N was present in virus from 51.3%, and V106M was present in virus from 19.1%. Thymidine analog resistance mutations were found in virus from 32.2% of patients, and protease resistance mutations were found in virus from 4.4%.Conclusions. Antiretroviral drug-resistant virus was detected in >80% of South African patients who experienced failure of a first HAART regimen. Patterns of drug resistance reflected drugs used in first-line regimens and viral subtype. Continued surveillance of resistance patterns is warranted to guide selection of second-line regimens.