Mohey Rajesh, Katzenstein Terese L, Black Finn T, Kjems Jørgen, Obel Niels
Department of Infectious Diseases, Skejby University Hospital, Aarhus, Denmark.
Scand J Infect Dis. 2006;38(2):119-23. doi: 10.1080/00365540500348937.
HIV-1 viral load falls rapidly on initiation of HAART. This phase of decreasing yet substantial viral production in the presence of antiretroviral drugs could generate resistant HIV-1. Whether switching a drug from a failing regime changes the demography of the mutations associated with it in the CD4+ T-cell compartment is not well-defined. We investigated the presence/absence and quantity of 184M and 184V in the CD4+ T-cell compartment of naïve patients initiated to HAART (group I), and patients who shifted to a non-lamivudine therapy (group II). We initiated a prospective 90 d follow-up study of 11 patients to detect and quantity proviral HIV-1 184M and 184V in the CD4+ T-cell compartment with a sensitive real time PCR assay. Results showed that the 184V was not detected in the CD4+ T-cell compartment of any of the 7 naïve patients who started on HAART. Three out of the 4 patients in group II experienced a fall in the percentage of 184V, with reduction to below detection limits in 2 patients. It can be concluded that initiation of HAART does not allow the archiving of the lamivudine associated mutation, 184V, in the CD4+ T-cell compartment. Reduction in the quantity of 184V when therapy is switched to an effective non-lamivudine regime indicates that the mutation in this compartment is dynamic.
开始高效抗逆转录病毒治疗(HAART)后,HIV-1病毒载量迅速下降。在抗逆转录病毒药物存在的情况下,病毒产生量虽在减少但仍可观的这一阶段可能会产生耐药的HIV-1。从失败方案中更换一种药物是否会改变CD4+T细胞区室中与其相关的突变分布尚不清楚。我们调查了开始接受HAART治疗的初治患者(第一组)以及转用非拉米夫定治疗的患者(第二组)的CD4+T细胞区室中184M和184V的有无及数量。我们对11名患者开展了一项为期90天的前瞻性随访研究,采用灵敏的实时PCR检测法来检测和定量CD4+T细胞区室中前病毒HIV-1的184M和184V。结果显示,开始接受HAART治疗的7名初治患者的CD4+T细胞区室中均未检测到184V。第二组的4名患者中有3名184V的百分比下降,其中2名患者降至检测限以下。可以得出结论,开始HAART治疗不会使拉米夫定相关突变184V在CD4+T细胞区室中存档。当治疗换用有效的非拉米夫定方案时,184V数量减少,这表明该区室中的突变是动态的。