Duani Helena, Aleixo Agdemir Waleria, Tupinambás Unaí
Universidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte, MG, Brazil; Universidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Belo Horizonte, MG, Brazil; Universidade Federal de Minas Gerais (UFMG), Laboratório de Imunologia e Biologia Molecular (DIP-UFMG), Belo Horizonte, MG, Brazil; Universidade Federal de Minas Gerais (UFMG), Hospital das Clínicas, Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais (UFMG), Laboratório de Imunologia e Biologia Molecular (DIP-UFMG), Belo Horizonte, MG, Brazil.
Braz J Infect Dis. 2017 Mar-Apr;21(2):148-154. doi: 10.1016/j.bjid.2016.11.009. Epub 2016 Dec 23.
Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS - 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS≥2″, when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years. Time trends of resistance were analyzed by Cochran-Armitage test. We observed a decrease in the rate resistance mutations for PI, NRTI, "IAS - 3 class mutations", and "No fully susceptible drugs" over these 11 years, from 69.2% to 20.7%, 92.3% to 90.2%, 46.2% to 22.5%, and 12.8% to 5.7%, respectively (p<0.05). Resistance to NNRTI increased from 74.4% to 81.6%, mainly because of K103N mutation. The GSS score ≥2 increased during the years from 35.9% to 87.3% (p<0.001). We demonstrate that resistance to PI and to the three main classes simultaneously are declining, although the number of patients on of antiretroviral therapy has doubled in the last ten years in Brazil (125,000 in 2002 to 400,000 in 2014). Broader resistance testing and the availability of more therapeutic options might have influenced this decline. The increase in NNRTI resistance can limit this class as first line treatment in Brazil in the future.
多项研究表明，耐多药HIV-1病毒的流行率正随着时间推移而下降。在巴西东南部米纳斯吉拉斯州（一个中等收入国家的州）进行了一项回顾性队列研究，以评估接受抗逆转录病毒治疗的人群中耐药性的变化趋势。我们分析了2002年至2012年期间来自米纳斯吉拉斯州52个城市的2115份HIV-1序列。根据以下定义对各组进行分析：“IAS-3类突变”，即如果每类中存在来自2015年IAS列表（耐药突变）中的≥1个耐药突变；“无完全敏感药物”，即斯坦福算法中不存在任何完全敏感药物；以及“GSS≥2”，即计算得出的最大GSS（基因型易感性评分）≥2或≥3，仅计算特定年份在巴西和美国可用的药物。通过 Cochr an-Armitage检验分析耐药性的时间趋势。我们观察到在这11年中，蛋白酶抑制剂（PI）、核苷类逆转录酶抑制剂（NRTI）、“IAS-3类突变”和“无完全敏感药物”的耐药突变率分别从69.2%降至20.7%、从92.3%降至90.2%、从46.2%降至22.5%以及从12.8%降至5.7%（p<0.05）。非核苷类逆转录酶抑制剂（NNRTI）的耐药性从74.4%增至81.6%，主要是由于K103N突变。这些年中GSS评分≥2从35.9%增至87.3%（p<0.001）。我们证明，尽管在过去十年中巴西接受抗逆转录病毒治疗的患者数量翻了一番（从2002年的12.5万增至2014年的40万），但对PI以及对这三类主要药物的同时耐药性正在下降。更广泛的耐药性检测以及更多治疗选择的可及性可能影响了这种下降。NNRTI耐药性的增加可能会限制其在未来巴西作为一线治疗药物的使用。
