Munerato Patricia, Sucupira Maria Cecilia, Oliveros Márcia P R, Janini Luiz Mario, de Souza Denise Ferreira, Pereira Anderson Alvarenga, Inocencio Lilian Amaral, Diaz Ricardo Sobhie
Infectious Diseases Division, Federal University of São Paulo, São Paulo, Brazil.
AIDS Res Hum Retroviruses. 2010 Mar;26(3):265-73. doi: 10.1089/aid.2008.0288.
In Brazil, where three distinct HIV-1 subtypes (B, F, and C) cocirculate, a significant portion of the HIV-infected population has been exposed to antiretroviral drugs. This study analyzes the antiretroviral resistance profiles of HIV-1-infected individuals failing antiretroviral therapy. Genotypic resistance profiles of 2474 patients presenting virologic failure to antiretroviral therapy in the city of São Paulo, Brazil, were generated and analyzed. Resistance mutations to protease inhibitors and nucleoside reverse transcriptase inhibitors were less common in subtype C viruses, whereas nonnucleoside reverse transcriptase inhibitor resistance mutations were less common in subtype F viruses. The thymidine analog mutation pathway known as pathway 1 was more prevalent in subtype B viruses than in subtype C viruses, whereas pathway 2 was more prevalent in subtype C viruses. Selected resistance mutations varied according to subtype for all three classes of antiretrovirals. We describe two distinct pathways of nonnucleoside reverse transcriptase inhibitor resistance (to nevirapine and efavirenz). Although cross-resistance to etravirine should occur more frequently among individuals failing nevirapine treatment, the prevalence of cross-resistance to etravirine, darunavir, and tipranavir was found to be low. We found that increases in the number of resistance mutations will be related to increases in the viral load. Special attention should be given to resistance profiles in non-B subtype viruses. The accumulation of knowledge regarding such profiles in the developing world is desirable.
在巴西，三种不同的HIV-1亚型（B、F和C）共同流行，很大一部分HIV感染人群已接触过抗逆转录病毒药物。本研究分析了抗逆转录病毒治疗失败的HIV-1感染者的抗逆转录病毒耐药谱。对巴西圣保罗市2474例抗逆转录病毒治疗出现病毒学失败的患者进行了基因耐药谱分析。C亚型病毒中对蛋白酶抑制剂和核苷类逆转录酶抑制剂的耐药突变较少见，而F亚型病毒中非核苷类逆转录酶抑制剂耐药突变较少见。称为途径1的胸苷类似物突变途径在B亚型病毒中比在C亚型病毒中更普遍，而途径2在C亚型病毒中更普遍。所有三类抗逆转录病毒药物的特定耐药突变因亚型而异。我们描述了非核苷类逆转录酶抑制剂（对奈韦拉平和依非韦伦）耐药的两种不同途径。虽然奈韦拉平治疗失败的个体中对依曲韦林的交叉耐药应该更频繁地发生，但发现对依曲韦林、达芦那韦和替拉那韦的交叉耐药率很低。我们发现耐药突变数量的增加与病毒载量的增加有关。应特别关注非B亚型病毒的耐药谱。在发展中国家积累有关此类谱的知识是可取的。
