Medeiros Melissa Soares, Arruda Erico Antônio Gomes, Guerrant Richard Littleton, Brown Christopher, Hammarskjold Marie-Louise, Rekosh David, Lima Aldo Angelo Moreira
Department of Pharmacology and Physiology, Federal University of Ceará, IBIMED, Brazil.
Braz J Infect Dis. 2007 Aug;11(4):390-4. doi: 10.1590/s1413-86702007000400003.
Genotype testing for HIV-1 drug resistance is useful for selecting antiretroviral drug regimens for patients experiencing therapeutic failure, but the optimal means for interpreting the test results is unknown because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance. This study identified common combinations of resistance mutations related to antiretroviral resistance profiles. From April 2002 to March 2004, 101 protease and RT sequences were determined for HIV-1 isolates from patients who were failing antiretroviral therapy. The resistance profile was evaluated using the Stanford Database program. Male patients predominated (76.2%), the median age was 38 years, the average CD4 count was 279.21 cells/mm(3) and the average viral load was 4.49 log. In relation to protease inhibitors (IP) 31 mutation patterns were detected, 49 mutation patterns were detected in Nucleoside RT Inhibitors (NRTI), and 17 patterns were found in the Non Nucleoside RT Inhibitors (NNRTI). K65R was detected in 5.9% of the isolates. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. The best antiretroviral susceptibility was found to be Lopinavir in the PI class and Tenofovir in the NRTI class. The top six mutation patterns accounted for 49% of the resistance to PI's, for 38.5% of NRTI resistance, and the top two mutation patterns accounted for 40.9% of resistance to NNRTI's.
对经历治疗失败的患者进行HIV-1耐药性基因分型检测，有助于选择抗逆转录病毒药物治疗方案，但由于许多HIV-1蛋白酶和逆转录酶（RT）突变会导致耐药性，解读检测结果的最佳方法尚不清楚。本研究确定了与抗逆转录病毒耐药谱相关的耐药突变常见组合。2002年4月至2004年3月，对接受抗逆转录病毒治疗失败患者的HIV-1分离株进行了101次蛋白酶和RT序列测定。使用斯坦福数据库程序评估耐药谱。男性患者居多（76.2%），中位年龄为38岁，平均CD4细胞计数为279.21个/mm³，平均病毒载量为4.49 log。关于蛋白酶抑制剂（PI），检测到31种突变模式，核苷类逆转录酶抑制剂（NRTI）检测到49种突变模式，非核苷类逆转录酶抑制剂（NNRTI）检测到17种模式。5.9%的分离株检测到K65R。最常见的突变分别是：与PI、NRTI和NNRTI相关的L90M、M184V和K103N。发现PI类中洛匹那韦的抗逆转录病毒敏感性最佳，NRTI类中替诺福韦最佳。前六种突变模式占PI耐药性的49%，NRTI耐药性的38.5%，前两种突变模式占NNRTI耐药性的40.9%。
