Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation
Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation
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DOI：
10.1097/00002030-200203080-00014
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发表时间：
2002-03-08
期刊：
影响因子：
3.8
通讯作者：
d'Arminio-Monforte, A
中科院分区：
文献类型：
--
作者：
Perno, CF;Cozzi-Lepri, A;d'Arminio-Monforte, A
目的：评估需要高效抗逆转录病毒治疗(HAART)的慢性感染HIV阳性患者中逆转录酶(RT)和蛋白水解酶(PR)区域突变的发生率。方法：该研究纳入意大利抗逆转录病毒初治患者队列(I.CO.NA)中347名必须开始HAART的患者。结果：基线血浆中CD_4~+淋巴细胞和HIV-RNA值分别为231×10~(6)Cells/L和4.89log(10)拷贝/ml；347例患者中，307例(88.5%)RT区无突变，40例(11.5%)携带一个或多个与核苷类逆转录酶抑制剂(NRTI)耐药相关的突变(7.8%)或非核苷类RT抑制药(NNRTI)耐药相关突变(4.9%)，其中4例同时携带突变。在与RTI高水平耐药相关的突变中，仅2例患者存在T215Y突变，2例患者存在M184V突变，另外2例患者存在T69D和T21 5C突变(各1例)，仅1例患者存在K103N突变，共6例患者(1例同时携带T215Y和M1 84V)(1.7%)。76例(21.9%)患者PR区无突变，271例(78.1%)患者PR区有一个或多个突变。在347例患者中，仅有5例(1.4%)发现了与蛋白水解酶抑制剂高度耐药相关的原发突变(M46V/L，154V，V82A/1)，其余患者仅携带二次突变(L10F/I/V，M361，L63P，A71T/V，V771)。这表明，在决定第一种治疗方案时，原则上不排除任何抗逆转录病毒药物。(C)2002年，里平科特·威廉姆斯·威尔金斯。
Objective: To assess the prevalence of mutations in the reverse-transcriptase (RT) and protease (PR) region in a cohort of chronically-infected HIV-positive patients requiring highly active antiretroviral therapy (HAART).Methods: The study included 347 patients enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA) who had to initiate HAART. The whole PR-region, and aminoacids 1-320 of RT-region were sequenced from plasma samples at baseline.Results: Median CD4-lymphocytes and HIV-RNA at baseline were 231 X 10(6) cells/l and 4.89 log(10) copies/ml; 307 of 347 (88.5%) patients carried no mutations in the RT region, whereas 40 (11.5%) carried one or more mutations associated with resistance to nucleoside-RT inhibitor (NRTI) (7.8%), or non-nucleoside-RTI (NNRTI) (4.9%), with four patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only two patients, M184V in two ases, T69D and T21 5C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M1 84V) (1.7%). Seventy-six patients (21.9%) carried no mutations in the PR region, whereas 271 (78.1%) had one or more mutations. Primary mutations associated with substantial resistance to protease inhibitors were found in only five of 347 patients (1.4%) (M46V/L, 154V, V82A/1); all the other patients carried only secondary mutations (L10F/I/V, M361, L63P, A71T/V, V771).Conclusions: Prevalence of mutations associated with high-level resistance to antiretroviral drugs is low in HIV-infected patients with long-term infection. This suggests no preclusion in principle to any antiretroviral drug at the time of decision of the first therapeutic regimen. (C) 2002 Lippincott Williams Wilkins.