目的:评估从未接受药物治疗的受试者收集的样本中检测到的RT-V106I多态性对多拉韦林的患病率和体外易感性。
方法:在含有V106I的定点突变体(SDM)中测量多拉韦林敏感性,V106A,在亚型B(NL4-3,HXB2)和CRF02_AG背景中的V106M和Y188L突变,以及在仅携带来自50PLWH的V106I的RT的重组病毒中。
结果:在1523/2705例中检测到HIV-1B亚型。V106I的患病率在B中为3.2%,在非B亚型中为2.5%,在F亚型中更高(8.1%),和D(14.3%)。对于V106I,SDM敏感性的倍数变化(FC)低于doravirine生物学截止值(3.0),但不是V106A,V106M,Y188L。测试的临床衍生病毒包括22个B(中位数FC1.2[IQR0.9-1.6])和28个非B亚型(中位数FC1.8[IQR0.9-3.0])。9种(18%)病毒的FC值等于或高于doravirine生物FC的临界值。
结论:MeditResHIV联盟中HIV-1RT-V106I多态性的患病率仍然很低,但在D亚型和F亚型中明显更普遍。V106I在SDM和大多数临床分离株中最低限度地降低了对多拉韦林的易感性。在F1亚型中,易感性降低似乎以增加的频率发生,但是临床影响仍有待研究。
BACKGROUND: Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to
doravirine.
METHODS: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106M, and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 people with HIV.
RESULTS: HIV-1 B subtype was detected in 1523 of 2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%) and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below
doravirine biological cutoff (3.0) for V106I, but not for V106A, V106M, and Y188L. Clinically derived viruses tested included 22 B (median FC, 1.2; interquartile range [IQR], 0.9-1.6) and 28 non-B subtypes (median FC, 1.8; IQR, 0.9-3.0). Nine (18%) viruses showed FC values equal or higher than the
doravirine biological FC cutoff.
CONCLUSIONS: The prevalence of the HIV-1 RT V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to
doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1; however, the clinical impact remains to be investigated.
BACKGROUND: NCT04894357.