Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
J Antimicrob Chemother. 2019 Feb 1;74(2):468-472. doi: 10.1093/jac/dky436.
Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho).
We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs. From Lesotho, individuals with two subsequent VLs ≥1000 copies/mL despite enhanced adherence counselling (n = 58) were included in the analysis. From Uganda, individuals with a single VL ≥1000 copies/mL (n = 120) were included in the analysis. From the Swiss HIV Cohort Study (SHCS), a population without history of monotherapy or dual therapy with the first GRT upon virological failure (n = 61) was selected.
We found that 50.8% of individuals in the SHCS, 72.5% in Uganda and 81.0% in Lesotho harboured HIV with high-level resistance to at least two drugs from their current regimen. Stanford resistance scores were higher in Uganda compared with Switzerland for all drugs used in first-line treatment except zidovudine and tenofovir (P < 0.01) and higher in Lesotho compared with Uganda for all drugs used in first-line treatment except zidovudine (P < 0.01).
Frequent VL monitoring and possibly pretreatment GRT as done in the SHCS pays off by low levels of resistance even when treatment failure occurs. The high-level resistance patterns in Lesotho compared with Uganda could reflect a selection of strains with multiple resistance during enhanced adherence counselling.
抗逆转录病毒药物的新出现的耐药性可能危及改善获得抗逆转录病毒治疗的成果。我们比较了在常规病毒载量（VL）监测（瑞士）以及VL 检测机会有限的队列（乌干达和莱索托）中发生病毒学失败的 HIV 感染成人中不同耐药突变的流行率。
我们考虑了在病毒学失败（≥1000 拷贝/毫升）时进行基因耐药性检测（GRT）并且正在接受至少一种 NNRTI 和两种 NRTI 治疗的个体。来自莱索托的个体在接受增强依从性咨询后仍有两次 VL≥1000 拷贝/毫升（n=58），也被纳入分析。来自乌干达的个体有一次 VL≥1000 拷贝/毫升（n=120），也被纳入分析。从瑞士艾滋病毒队列研究（SHCS）中，选择了一组在病毒学失败时第一次 GRT 没有经历过单药或二联疗法的个体（n=61）。
我们发现，SHCS 中的 50.8%、乌干达的 72.5%和莱索托的 81.0%的个体携带的 HIV 对其当前方案中的至少两种药物具有高水平耐药性。与瑞士相比，乌干达的所有一线治疗药物（除齐多夫定和替诺福韦外）的斯坦福耐药评分均较高（P<0.01），莱索托的所有一线治疗药物（除齐多夫定外）的斯坦福耐药评分均较高（P<0.01）。
即使在治疗失败时，频繁的 VL 监测和可能的治疗前 GRT （如 SHCS 所做的那样）通过低水平的耐药性得到了回报。与乌干达相比，莱索托的高水平耐药模式可能反映了在增强依从性咨询期间对具有多种耐药性的菌株的选择。
