2006 年至 2016 年意大利传播的 HIV-1 耐药性和病毒亚型流行的演变。
Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.
机构信息
Infectious Diseases Unit, University Hospital of Siena, Siena, Italy.
Clinic of Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
出版信息
HIV Med. 2018 Oct;19(9):619-628. doi: 10.1111/hiv.12640. Epub 2018 Jun 22.
OBJECTIVES
The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016.
METHODS
HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list.
RESULTS
We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169-521 cells/μL], and the median viral load was 4.7 log HIV-1 RNA copies/mL (IQR 4.1-5.3 log copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02).
CONCLUSIONS
The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.
目的
评估 2006 年至 2016 年期间在未接受抗逆转录病毒治疗（ART）的患者中传播的 HIV-1 耐药性（TDR）流行率的变化。
方法
从抗病毒反应队列分析（ARCA）数据库中检索 HIV-1 序列，将 TDR 定义为至少检测到一种来自世界卫生组织（WHO）监测清单的突变。
结果
我们纳入了 3573 名患者的蛋白酶/逆转录酶序列；其中 455 名患者还具有整合酶序列。总体而言，68.1%的患者为意大利人，中位 CD4 计数为 348 个细胞/μL [四分位间距（IQR）169-521 个细胞/μL]，中位病毒载量为 4.7 log HIV-1 RNA 拷贝/mL（IQR 4.1-5.3 log 拷贝/mL）。在 10.3%的患者中检测到 TDR：6%的患者携带核苷（酸）逆转录酶抑制剂（NRTIs）突变，4.4%的患者携带非核苷（酸）逆转录酶抑制剂（NNRTIs）突变，2.3%的患者携带蛋白酶抑制剂（PI）突变，0.2%的患者携带整合酶链转移抑制剂（INSTIs）突变，2.1%的患者携带至少两种药物类别。TDR 从 2006 年的 14.5%下降到 2016 年的 7.3%（P = 0.003）：NRTIs 的 TDR 从 9.9%下降到 2.9%（P = 0.003），NNRTIs 的 TDR 从 5.1%下降到 3.7%（P = 0.028）；PI 的 TDR 保持稳定。携带 B 亚型病毒的比例从 76.5%下降到 50%（P < 0.001）。B 亚型与非 B 亚型的 TDR 发生率分别为 12.6%和 4.9%（分别为；P < 0.001），B 亚型的 TDR 显著下降（从 17.1%下降到 8.8%；P = 0.04），而非 B 亚型的 TDR 没有显著下降（从 6.1%下降到 5.8%；P = 0.44）。调整来源国后，TDR 的预测因素为 B 亚型（B 亚型与非 B 亚型的调整优势比（AOR）为 2.91；95%置信区间（CI）为 1.93-4.39；P < 0.001）、较低的病毒载量（每增加一个对数：AOR 0.86；95%CI 0.75-0.99；P = 0.03）、意大利北部的地点（与意大利南部/岛屿相比，意大利北部的 AOR 为 0.61；95%CI 为 0.40-0.91；P = 0.01）和较晚的日历年份（每增加 1 年：AOR 0.95；95%CI 0.91-0.99；P = 0.02）。
结论
在过去的 10 年中，意大利的 HIV-1 TDR 流行率有所下降。
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