Department of Epidemiology, University of Washington, Seattle.
Department of Global Health, University of Washington, Seattle.
J Infect Dis. 2017 Dec 19;216(12):1569-1578. doi: 10.1093/infdis/jix544.
Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort.
We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios.
PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004).
The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance.
NCT01898754.
治疗前药物耐药性(PDR)是人类免疫缺陷病毒(HIV)治疗失败的预测因素。我们在肯尼亚队列中确定了 PDR 的流行率及其相关因素。
我们对接受抗逆转录病毒(ARV)治疗的 HIV 感染参与者进行了横断面分析。通过寡核苷酸连接检测和 Illumina 测序,在 pol 密码子 K103N、Y181C、G190A、M184V 或 K65R 处,当参与者的 HIV 准种中存在≥2%的突变频率时,定义为 PDR。根据人口统计学和密码子进行分层,计算 PDR 的流行率,并按先前的 ARV 经验进行分层。使用泊松回归估计流行率比。
815 名 ARV 初治成年人、136 名 ARV 经验丰富的成年人和 36 名主要 ARV 初治儿童中,PDR 的流行率(95%置信区间[CI])分别为 9.4%(7.5%-11.7%)、12.5%(7.5%-19.3%)和 2.8%(0.1%-14.5%)。个体 HIV 准种内的突变频率中位数为 67%。18-24 岁 ARV 初治女性的 PDR 流行率为 21.9%(9.3%-40.0%)。只有女性的年龄与 PDR 相关:年龄每减少 5 岁,调整后的 PDR 流行率比为 1.20(95%CI,1.06-1.36;P=0.004)。
高 PDR 流行率可能需要在 HIV 高流行地区进行耐药性检测和/或使用替代 ARV,同时关注年轻女性,因为她们可能最近感染,耐药率更高。
NCT01898754。