Chkhartishvili N, Dvali N, Gochitashvili N, Sharvadze L, Tsertsvadze T
Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia.
Georgian Med News. 2008 Dec(165):16-22.
Since 2004, Georgia the first among Eastern European countries ensured universal access to highly active antiretroviral therapy (HAART). Laboratory monitoring of HAART using CD4 count, viral load (VL) and HIV genotypic resistance testing was carried out in according with National HIV/AIDS Treatment Guidelines. Georgia the first among former Soviet Union countries implemented HIV genotypic resistance testing in HIV clinical care. The present paper reports on successful application of laboratory tools in routine clinical care for the early detection of HIV drug resistance. For genotypic resistance testing the TruGene HIV-1 Genotyping Kit (Bayer HealthCare LLC, Tarrytown, NY) was used according to manufacturer's instructions. Analysis included 45 patients with virologic failure. Of them 34 (75.5%) had at least one resistant mutation. Dual-class drug resistance was found in 30 (66.7%) patients. One (2.2%) patient carried triple-class resistance mutations. Median number of resistant mutations was 2. Most commonly detected NRTI mutation was M184/V/I (68.9%). G190S/A was the most frequent NNRTI mutation (42.2%), followed by K103N (28.9%). All patients with drug resistance mutations were switched to a second line regimens. Analysis of virologic and immunological outcomes among 23 patients who had at least two follow-up measurements of CD4 and VL after resistance test, showed statistically significant decrease in VL by 2.5 log(10) and mean gain of 181 cells/mm(3) in CD4 count by the last available measurement. Routine monitoring of VL and subsequent use of HIV drug resistance testing allowed for early identification of HIV drug resistance, reducing the opportunity for mutations to accumulate. Routine use of sophisticated laboratory methods for HAART monitoring has beneficial impact on clinical outcomes and should be used as part of the strategy to combat resistance.
自2004年以来,格鲁吉亚是东欧国家中首个确保普遍可获得高效抗逆转录病毒疗法(HAART)的国家。根据国家艾滋病毒/艾滋病治疗指南,利用CD4细胞计数、病毒载量(VL)和艾滋病毒基因型耐药性检测对HAART进行实验室监测。格鲁吉亚是前苏联国家中首个在艾滋病毒临床护理中实施艾滋病毒基因型耐药性检测的国家。本文报告了实验室工具在常规临床护理中成功应用以早期检测艾滋病毒耐药性的情况。对于基因型耐药性检测,根据制造商的说明使用了TruGene HIV-1基因分型试剂盒(拜耳医疗保健有限责任公司,纽约州塔里敦)。分析纳入了45例病毒学治疗失败的患者。其中34例(75.5%)至少有一个耐药突变。30例(66.7%)患者存在双重耐药。1例(2.2%)患者携带三重耐药突变。耐药突变的中位数为2。最常检测到的核苷类逆转录酶抑制剂(NRTI)突变是M184/V/I(68.9%)。G190S/A是最常见的非核苷类逆转录酶抑制剂(NNRTI)突变(42.2%),其次是K103N(28.9%)。所有有耐药突变的患者都改用了二线治疗方案。对23例在耐药性检测后至少有两次CD4细胞计数和VL随访测量结果的患者的病毒学和免疫学结果分析显示,最后一次可用测量时VL有统计学意义地下降了2.5 log(10),CD4细胞计数平均增加了181个细胞/mm³。对VL进行常规监测并随后使用艾滋病毒耐药性检测能够早期识别艾滋病毒耐药性,减少突变积累的机会。常规使用复杂的实验室方法进行HAART监测对临床结果有有益影响,应作为抗耐药策略的一部分加以应用。