PDF(Pubmed)
Abstract：
UNASSIGNED: An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretroviral therapy (ART), with the majority of them unaware of their drug resistance status. In this study, we assessed the prevalence of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors, and the variables associated with drug resistance in patients failing treatment in Nairobi, Kenya.This cross-sectional study utilized 128 HIV-positive plasma samples obtained from patients enrolled for routine viral monitoring in Nairobi clinics between 2015 and 2017. The primary outcome was human immunodeficiency virus type 1 (HIV-1) drug resistance mutation counts determined by Sanger sequencing of the polymerase (pol) gene followed by interpretation using Stanford\'s HIV Drug Resistance Database. Poisson regression was used to determine the effects of sex, viral load, age, HIV-subtype, treatment duration, and ART-regimen on the primary outcome.HIV-1 drug resistance mutations were found in 82.3% of the subjects, with 15.3% of subjects having triple-class ART resistance and 45.2% having dual-class resistance. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. We found statistically significant evidence (P = .013) that the association between treatment duration and drug resistance mutations differed by sex. An increase of one natural-log transformed viral load unit was associated with 11% increase in drug resistance mutation counts (incidence rate ratio [IRR] 1.11; 95% CI 1.06-1.16; P < .001) after adjusting for age, HIV-1 subtype, and the sex-treatment duration interaction. Subjects who had been on treatment for 31 to 60 months had 63% higher resistance mutation counts (IRR 1.63; 95% CI 1.12-2.43; P = .013) compared to the reference group (<30 months). Similarly, patients on ART for 61 to 90 months were associated with 133% higher mutation counts than the reference group (IRR 2.33; 95% CI 1.59-3.49; P < .001). HIV-1 subtype, age, or ART-regimen were not associated with resistance mutation counts.Drug resistance mutations were found in alarmingly high numbers, and they were associated with viral load and treatment time. This finding emphasizes the importance of targeted resistance monitoring as a tool for addressing the problem.
摘要：
未经批准：估计有150万肯尼亚人是艾滋病毒血清呈阳性，有110万人接受抗逆转录病毒治疗（ART），他们中的大多数人不知道他们的耐药状况。在这项研究中,我们评估了核苷逆转录酶抑制剂（NRTIs）的耐药性，核苷逆转录酶抑制剂（NNRTIs），和蛋白酶抑制剂，以及与内罗毕治疗失败患者的耐药性相关的变量，肯尼亚。这项横断面研究使用了从2015年至2017年在内罗毕诊所进行常规病毒监测的患者中获得的128份HIV阳性血浆样本。主要结果是人类免疫缺陷病毒1型（HIV-1）耐药性突变计数，通过聚合酶（pol）基因的Sanger测序确定，然后使用Stanford的HIV耐药性数据库进行解释。泊松回归用于确定性别的影响，病毒载量,年龄,HIV亚型,治疗持续时间,和ART方案的主要结果。在82.3%的受试者中发现了HIV-1耐药突变,15.3%的受试者有三类ART抵抗，45.2%的受试者有双类抵抗。NRTI原发突变M184V/I和K65R/E/N分别在28.8%和8.9%的受试者中发现,而NNRTI主要突变K103N/S,G190A,Y181C的含量为21.0%，14.6%,和10.9%的科目。我们发现有统计学意义的证据（P=0.013）表明治疗持续时间和耐药突变之间的关联因性别而异。一个自然对数转化病毒载量单位的增加与耐药突变计数增加11％相关（发病率比[IRR]1.11;95％CI1.06-1.16;P<.001），HIV-1亚型,以及性别-治疗持续时间的相互作用。与参考组（<30个月）相比，接受治疗31至60个月的受试者的耐药突变计数高63％（IRR1.63；95％CI1.12-2.43；P=0.013）。同样，接受ART治疗61~90个月的患者突变计数比参照组高133%(IRR2.33;95%CI1.59~3.49;P<.001).HIV-1亚型,年龄,或ART方案与耐药突变计数无关.发现耐药突变的数量惊人地高，它们与病毒载量和治疗时间有关。这一发现强调了有针对性的耐药性监测作为解决问题的工具的重要性。
