Perno Carlo Federico, Cozzi-Lepri Alessandro, Balotta Claudia, Bertoli Ada, Violin Michela, Monno Laura, Zauli Tiziano, Montroni Maria, Ippolito Giuseppe, d'Arminio-Monforte Antonella
IRCCS L. Spallanzani Hospital, Via Portuense 292, 00149 Rome, Italy.
AIDS. 2002 Mar 8;16(4):619-24. doi: 10.1097/00002030-200203080-00014.
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).
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 amino acids 1-320 of RT-region were sequenced from plasma samples at baseline.
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 cases, T69D and T215C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M184V) (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, I54V, V82A/I); all the other patients carried only secondary mutations (L10F/I/V, M36I, L63P, A71T/V, V77I).
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.
评估一组需要接受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）和蛋白酶（PR）区域的突变率。
该研究纳入了347名意大利初治抗逆转录病毒患者队列（I.CO.NA）中必须开始HAART治疗的患者。在基线时从血浆样本中对整个PR区域以及RT区域的第1至320位氨基酸进行测序。
基线时CD4淋巴细胞中位数和HIV-RNA分别为231×10⁶个细胞/升和4.89 log₁₀拷贝/毫升；347名患者中有307名（88.5%）在RT区域未发生突变，而40名（11.5%）携带一个或多个与对核苷类RT抑制剂（NRTI）耐药相关的突变（7.8%），或与非核苷类RT抑制剂（NNRTI）耐药相关的突变（4.9%），4名患者同时携带这两类突变。在与对RTI高水平耐药相关的突变中，仅在2名患者中发现T215Y，2例发现M184V，另外2例（各1例）发现T69D和T215C，仅1名患者发现K103N，共6名患者（1名同时携带T215Y和M184V）（1.
