Booth Clare L, Garcia-Diaz Ana M, Youle Michael S, Johnson Margaret A, Phillips Andrew, Geretti Anna Maria
Department of Virology, Royal Free Hospital and Royal Free & University College Medical School, London, UK.
J Antimicrob Chemother. 2007 Mar;59(3):517-24. doi: 10.1093/jac/dkl501. Epub 2007 Jan 9.
To determine prevalence and predictors of antiretroviral drug resistance in newly diagnosed individuals with HIV-1 infection, using a systematic approach to avoid selection bias.
Plasma samples from all persons diagnosed HIV-1 seropositive at a large London centre between April 2004 and February 2006 underwent sequencing of HIV-1 reverse transcriptase (RT) and protease genes. Subtype was assigned by phylogenetic analysis. Resistance was scored according to the IAS-USA list (2005) modified to include T215revertants and exclude isolated E44D or V118I and minor protease mutations. Recent seroconversion was identified by HIV antibody avidity testing.
The cohort of 239 included 169 (70.7%) males, 126 (52.7%) homosexuals, 118 (49.5%) persons of white ethnicity and 144 (60.0%) persons born outside the UK. Subtypes included B 134 (56.1%), C 46 (19.2%), A 17 (7.1%), other non-B 42 (17.6%). The prevalence of resistance mutations was 17/239 (7.1%; 95% confidence interval 4.5-11.1%), comprising 10/239 (4.2%) nucleoside/nucleotide RT inhibitor (NRTI); 4/239 (1.7%) non-nucleoside RT inhibitor (NNRTI) and 4/239 (1.7%) protease inhibitor (PI) associated mutations. Dual-class (NRTI + PI) resistance mutations were detected in 1/239 (0.4%) person. The prevalence of resistance mutations was 7/85 (8.2%) and 10/154 (6.5%) in persons with recent and established infection, respectively. In multivariate analysis, having been born in the UK and high CD4 count, but not gender, age, risk group, ethnicity or subtype, were independent predictors of resistance.
In an unselected UK cohort, subtypes other than B accounted for 43.9% of new HIV-1 diagnoses. The prevalence of resistance mutations was 7.1% and highest in those born in the UK.
采用系统方法以避免选择偏倚，确定新诊断的HIV-1感染者中抗逆转录病毒药物耐药性的流行情况及预测因素。
对2004年4月至2006年2月间在伦敦一个大型中心诊断为HIV-1血清阳性的所有人的血浆样本进行HIV-1逆转录酶（RT）和蛋白酶基因测序。通过系统发育分析确定亚型。根据经修改的IAS-美国列表（2005年）对抗药性进行评分，修改内容包括纳入T215回复突变体并排除孤立的E44D或V118I以及蛋白酶小突变。通过HIV抗体亲和力检测确定近期血清转化情况。
239名研究对象中，男性169名（70.7%），同性恋者126名（52.7%），白人118名（49.5%），出生于英国境外者144名（60.0%）。亚型包括B型134名（56.1%）、C型46名（19.2%）、A型17名（7.1%）、其他非B型42名（17.6%）。耐药突变的流行率为17/239（7.1%；95%置信区间4.5 - 11.1%），包括10/239（4.2%）核苷/核苷酸逆转录酶抑制剂（NRTI）；4/239（1.7%）非核苷逆转录酶抑制剂（NNRTI）和4/239（1.7%）蛋白酶抑制剂（PI）相关突变。在1/239（0.4%）的研究对象中检测到双重耐药（NRTI + PI）突变。近期感染和已确诊感染的研究对象中耐药突变的流行率分别为7/85（8.2%）和10/154（6.5%）。在多变量分析中，出生在英国和高CD4计数是耐药的独立预测因素，而非性别、年龄、风险组、种族或亚型。
在一个未经过选择分组的英国队列中，除B型外的其他亚型占新HIV-1诊断病例的43.9%。耐药突变的流行率为7.1%，在出生于英国的人群中最高。
