Birk M, Sönnerborg A
Division of Clinical Virology, Huddinge University Hospital, Karolinska Institute, Sweden.
AIDS. 1998 Dec 24;12(18):2369-75. doi: 10.1097/00002030-199818000-00005.
Various drugs against the HIV-1 enzymes reverse transcriptase (RT) and protease have been introduced in the last few years: protease inhibitors, nucleoside RT inhibitors (NRTI) and non-NRTI (NNRTI). Several sequence variations associated with reduced drug sensitivity have been described in the HIV-1 pol gene.
To analyse the occurrence of mutations associated with drug resistance in treatment-naive individuals.
RNA was extracted from sera of treatment-naive individuals, who were first diagnosed to be HIV-1 infected between August 1996 and February 1998. The pol region was amplified by RT-PCR and directly sequenced. Data on mutations associated with resistance to antiretroviral drugs were obtained from literature.
Fifty protease genes and 53 RT genes from 57 individuals were sequenced. In the RT we analysed 20 amino-acid positions associated with resistance to NRTI and NNRTI. In total, 1054 amino acids at critical positions were analysed and three (0.3%) mutations known to contribute to RTI resistance were detected. In the protease, 16 amino-acid positions associated with resistance to protease inhibitors were analysed. By analysing a total of 768 amino acids at key positions in the protease, 50 (7%) mutations were detected that were associated with reduced drug sensitivity. Thirty-one (61%) patients showed between one and six mutations at the analysed protease amino-acid positions. In eight out of 16 analysed amino-acid positions, up to 44% of all patients carried mutations associated with resistance to protease inhibitors.
Very few pre-existing mutations to RTI were found, suggesting that the transmission of RT-resistant strains is still uncommon. However, about two-thirds of the patients had one or more mutations associated with resistance to protease inhibitors. In addition, at some amino-acid positions up to almost half of the patients carried variations claimed to contribute to protease inhibitor resistance. Most of these mutations are likely to reflect the natural polymorphism of the protease. Their impact on the long-term effect of antiretroviral treatment should be evaluated in future studies.
在过去几年中已引入了多种针对人类免疫缺陷病毒1型（HIV-1）酶逆转录酶（RT）和蛋白酶的药物：蛋白酶抑制剂、核苷类逆转录酶抑制剂（NRTI）和非核苷类逆转录酶抑制剂（NNRTI）。HIV-1 pol基因中已描述了几种与药物敏感性降低相关的序列变异。
分析初治个体中与耐药相关的突变的发生情况。
从1996年8月至1998年2月首次被诊断为HIV-1感染的初治个体的血清中提取RNA。通过逆转录聚合酶链反应（RT-PCR）扩增pol区域并直接测序。从文献中获取与抗逆转录病毒药物耐药相关的突变数据。
对57名个体的50个蛋白酶基因和53个RT基因进行了测序。在RT中，我们分析了20个与对NRTI和NNRTI耐药相关的氨基酸位置。总共分析了关键位置的1054个氨基酸，检测到3个（0.3%）已知导致对RTI耐药的突变。在蛋白酶中，分析了16个与对蛋白酶抑制剂耐药相关的氨基酸位置。通过分析蛋白酶关键位置的总共768个氨基酸，检测到50个（7%）与药物敏感性降低相关的突变。31名（61%）患者在分析的蛋白酶氨基酸位置显示1至6个突变。在16个分析的氨基酸位置中的8个位置，所有患者中高达44%携带与对蛋白酶抑制剂耐药相关的突变。
发现对RTI预先存在的突变非常少，这表明对RT耐药毒株的传播仍然不常见。然而，约三分之二的患者有一个或多个与对蛋白酶抑制剂耐药相关的突变。此外
