Calva Juan J, Larrea Silvana, Tapia-Maltos Marco A, Ostrosky-Frid Mauricio, Lara Carolina, Aguilar-Salinas Pedro, Rivera Héctor, Ramírez Juan P
1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
2 PECEM, Faculty of Medicine, Universidad Nacional Autónoma de México , Mexico City, Mexico .
AIDS Res Hum Retroviruses. 2017 Jul;33(7):675-680. doi: 10.1089/AID.2016.0248. Epub 2017 Feb 21.
A decrease in the rate of acquired antiretroviral (ARV) drug resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virological failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nucleos(t)ide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitor (PI) resistance-associated mutations (RAMs). Patients were divided into two groups according to their first ART start date: 488 patients initiated ART before mid-2003 (group 1) and 486 after mid-2003 (group 2). The rate of RAMs, median resistance score of several sentinel ARVs, and composition of ART drugs in patient's entire treatment history were compared between both groups. Patients in group 2 were less likely to have >3 thymidine analogue-associated mutations (TAMs) and >3 PI-mRAMs [adjusted odds ratio (aOR) = 0.37; 95% confidence interval (95% CI) = 0.25-0.54; p < .001 and aOR = 0.53; 95% CI = 0.36-0.77; p = .001, respectively] and had a significantly lower resistance score for zidovudine, tenofovir, ritonavir-boosted (r)-lopinavir, r-atazanavir, and r-darunavir than group 1 patients. A significantly lower proportion of patients in group 2 used monotherapy, bitherapy, thymidine analogue-containing regimens, nonboosted PI-containing regimens, and low resistance barrier PI-containing regimens. In Mexican ARV-experienced patients, the occurrence of TAM and PI-mRAM has significantly declined over time. This can be explained by treatment optimization in the national ART roll-out program in recent years.
在高收入地区，随着时间推移获得性抗逆转录病毒（ARV）药物耐药性（ADR）发生率有所下降，这一点已有记录，但关于这一现象的决定因素的数据却很缺乏。我们检验了这样一个假设：在墨西哥ARV治疗（ART）推广项目中，有丰富ARV治疗经验的患者中，ADR的下降与ARV药物使用的变化有关。对从全国974例病毒学治疗失败且至少有2种先前治疗失败的ARV治疗方案的HIV感染患者获得的基因型耐药性检测结果进行分析，以确定是否存在核苷（酸）逆转录酶抑制剂、非核苷逆转录酶抑制剂和蛋白酶抑制剂（PI）耐药相关突变（RAMs）。根据患者首次开始ART的日期将患者分为两组：488例患者在2003年年中之前开始ART（第1组），486例在2003年年中之后开始ART（第2组）。比较两组患者的RAMs发生率、几种哨点ARV的中位耐药评分以及患者整个治疗史中ART药物的组成。第2组患者发生>3个胸苷类似物相关突变（TAM）和>3个PI-mRAMs的可能性较小[调整优势比（aOR）=0.37；95%置信区间（95%CI）=0.25 - 0.54；p<0.001和aOR = 0.53；95%CI = 0.36 - 0.77；p = 0.001]，并且齐多夫定、替诺福韦、利托那韦增强（r）-洛匹那韦、r-阿扎那韦和r-达芦那韦的耐药评分显著低于第1组患者。第2组患者中使用单药治疗、双药治疗、含胸苷类似物方案、非增强PI方案和低耐药屏障PI方案的比例显著较低。在有ARV治疗经验的墨西哥患者中，TAM和PI-mRAM的发生率随时间显著下降。这可以通过近年来国家ART推广项目中的治疗优化来解释。
