Marconi Vincent C, Sunpath Henry, Lu Zhigang, Gordon Michelle, Koranteng-Apeagyei Kofi, Hampton Jane, Carpenter Steve, Giddy Janet, Ross Douglas, Holst Helga, Losina Elena, Walker Bruce D, Kuritzkes Daniel R
Section of Retroviral Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02139, USA.
Clin Infect Dis. 2008 May 15;46(10):1589-97. doi: 10.1086/587109.
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.
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 > or =1 significant drug resistance mutation.
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 > or =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%.
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.
1型人类免疫缺陷病毒(HIV-1)耐药性的出现可能会限制资源有限地区抗逆转录病毒疗法的疗效。在南非夸祖鲁-纳塔尔省的患者首次高效抗逆转录病毒疗法(HAART)方案失败后,评估了耐药性的流行情况。
对夸祖鲁-纳塔尔省两家诊所中首次HAART方案出现病毒学失败的患者的血浆病毒样本进行基因耐药性检测。从医疗记录中获取临床和人口统计学数据。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,共纳入124名接受抗逆转录病毒治疗且出现病毒学失败的成年人。主要亚型为HIV-1C。83.5%的参与者的病毒样本携带≥1个显著耐药突变。双重耐药病毒存在于64.3%的参与者中,2.6%的参与者的病毒具有三重耐药性。最常见的突变是M184V/I(64.3%的患者);K103N存在于51.3%的病毒中,V106M存在于19.1%的病毒中。32.2%的患者的病毒中发现了胸苷类似物耐药突变,4.4%的患者的病毒中发现了蛋白酶耐药突变。
在首次HAART方案失败的南非患者中,超过80%检测到了抗逆转录病毒耐药病毒。耐药模式反映了一线方案中使用的药物和病毒亚型。有必要持续监测耐药模式以指导二线方案的选择。