Department of Microbiology and Immunology, Minderbroedersstraat 10, 3000 Leuven, KU Leuven, Leuven, Belgium.
J Antimicrob Chemother. 2013 Apr;68(4):911-4. doi: 10.1093/jac/dks470. Epub 2012 Dec 9.
Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal.
We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR.
We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen.
The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.
尽管接受高效抗逆转录病毒治疗(HAART)的 HIV-1 患者的死亡率和发病率有所下降,但仍可能因耐药性的发展而导致治疗失败。特别是,多药耐药病毒对高效治疗构成威胁。我们研究了葡萄牙一组 HIV-1 感染患者中多药耐药(MDR)随时间的变化流行率。
我们使用了 2001 年 7 月至 2012 年 4 月期间在葡萄牙 22 家医院接受治疗的 8065 名 HIV-1 感染患者的数据。采样时的 MDR 定义为当时葡萄牙国家药品和保健品管理局(INFARMED)授权的一种以上完全有效的药物(不包括整合酶和进入抑制剂)不超过一种,该定义根据 Rega 算法版本 8.0.2 进行解释。使用广义线性混合模型研究 MDR 流行率的时间趋势。
我们观察到,在过去十年中,MDR 的流行率呈统计学显著下降,从 2001-03 年的 6.9%(95%CI:5.7-8.4)、2003-05 年的 6.0%(95%CI:4.9-7.2)、2005-07 年的 3.7%(95%CI:2.8-4.8)和 2007-09 年的 1.6%(95%CI:1.1-2.2)降至 2009-12 年的 0.6%(95%CI:0.3-0.9)[比值比=0.80(95%CI:0.75-0.86);P<0.001]。2011 年 7 月最后一次出现新的 MDR 病例。
葡萄牙的 HIV-1 多药耐药率随时间呈下降趋势,反映了 HAART 效率的提高和新药的可用性。因此,在设计新药时,安全性和实用性方面,例如毒性较小和使用方便,可能需要比主要关注耐药菌株的疗效更多的关注。