Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses
Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses
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DOI：
10.1093/jac/dkt003
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发表时间：
2013-06-01
影响因子：
5.2
通讯作者：
Marcelin, A. -G.
中科院分区：
文献类型：
--
作者：
Lambert-Niclot, S.;Charpentier, C.;Marcelin, A. -G.
在体内和体外描述的利匹韦林、恩曲他滨和替诺福韦耐药相关突变（RAMs）的患病率在抗逆转录病毒初始患者中被确定。从2008年到2011年，通过批量测序对1729例首次接受治疗的患者进行了耐药性检测。我们研究了原发性利匹韦林突变（K101E/P、E138A/G/K/Q/R、V179L、Y181C/I/V、H221Y、F227C和M230I/L）和其他潜在的利匹韦林相关突变（V90I、L100I、K101T、E138S、V179D/I、Y188L、V189I、G190A/E/S和M230V）。我们还分别研究了恩曲他滨和替诺福韦的M184V/I和K65R突变。在1729个序列中，一半患者携带b亚型病毒，另一半患者携带非b亚型病毒（CRF02为26.7,n461）。原发性利匹韦林RAMs少见（4.6,n79），最常见的是E138A （3, n52）、E138K （0.3, n5）、H221Y （0.3, n5）、E138G （0.2, n4）和Y181C （0.2, n4）。原发性利匹韦林RAMs的频率在B亚型和非B亚型之间相似。其他潜在的利匹韦林相关突变最普遍的是V179I (8.4, n145), V90I （3.8, n65）和V189I （2.3, n40）。在3期临床研究中，常见的V179I、V189I和V90I多态性与病毒学失败无关。通过ANRS算法，对利匹韦林耐药的样本为4.9份（n84份），其中b亚型病毒为3.7份（n32份），非b亚型病毒为6份（n52份）（P0.02,(2)检验）。K65R和M184I/V的患病率分别为0.06（1/1729）和1（18/1729）。K103N的患病率为2（35/1729）。利匹韦林、恩曲他滨和替诺福韦耐药突变在抗逆转录病毒初始患者中非常低。在我们的人群中，利匹韦林的耐药率（4.9,n84）与依非韦伦和奈韦拉平的耐药率无统计学差异。
The prevalence of rilpivirine, emtricitabine and tenofovir resistance-associated mutations (RAMs), described in vitro and in vivo, was determined in antiretroviral-naive patients.From 2008 to 2011, 1729 treatment-naive patients were tested for resistance by bulk sequencing. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively.Among 1729 sequences, half of patients had B-subtype viruses and the other half non-B (with 26.7 CRF02, n461). Primary rilpivirine RAMs were infrequent (4.6, n79) and the most prevalent were E138A (3, n52), E138K, (0.3, n5), H221Y (0.3, n5), E138G (0.2, n4) and Y181C (0.2, n4). The frequency of the primary rilpivirine RAMs was similar between B and non-B subtypes. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4, n145), V90I (3.8, n65) and V189I (2.3, n40). The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. By the ANRS algorithm, 4.9 (n84) of samples were resistant to rilpivirine, 3.7 (n32) of B-subtype viruses versus 6 (n52) of non-B-subtype viruses (P0.02, (2) test). The prevalence of K65R and M184I/V was 0.06 (1/1729) and 1 (18/1729), respectively. The prevalence of K103N was 2 (35/1729).The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients. The prevalence of resistance to rilpivirine (4.9, n84) was not statistically different from the prevalence of efavirenz and nevirapine resistance in our population.