Polilli Ennio, Parruti Giustino, Cosentino Luana, Sozio Federica, Saracino Annalisa, Consorte Augusta, Angarano Gioacchino, Di Masi Francesco, Mazzotta Elena, Fazii Paolo
Clinical Pathology Unit, Ospedale Civile "Spirito Santo", Via Fonte Romana 8, 65124 Pescara, Italy.
J Med Case Rep. 2009 Sep 18;3:9132. doi: 10.4076/1752-1947-3-9132.
Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo.
A 55-year-old Caucasian man was switched to efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression in his first-line highly active anti-retroviral treatment regimen. One month later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He did not attend further checkups until September 2005, when his viral load was 181,000 c/mL. The patient reported interrupting his medications approximately three weeks after simplification. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain.
Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz.
K103N突变的选择与HIV体外适应性适度降低有关。体内携带K103N的毒株往往会持续存在,即使在没有额外药物压力的情况下,作为少数准种,在标准条件下进行的基因分型耐药性检测试验中通常无法检测到。在此,我们报告了在体内极短时间接触依非韦伦后,携带K103N的毒株迅速且持久地被选择成为优势准种。
一名55岁的白人男性在2003年2月改用依非韦伦、齐多夫定和拉米夫定,当时他正在接受一线高效抗逆转录病毒治疗方案且病毒得到抑制。一个月后,他报告依从性不一致,病毒血症水平为5700拷贝/毫升。直到2005年9月他才再次接受检查,此时他的病毒载量为181,000拷贝/毫升。患者报告在简化治疗方案约三周后中断了用药。对血浆中的HIV RNA和HIV DNA都进行了基因分型耐药性检测试验,结果显示优势毒株中存在K103N突变,二者结果相同。
在极短时间接触依非韦伦后,K103N突变可能会作为主要准种持续存在。因此,我们的病例表明,即使是极少量接触依非韦伦后,也应通过基因分型耐药性检测试验排除K103N突变的存在。