Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I
Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I
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DOI：
10.1093/infdis/jiz631
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发表时间：
2020-10-01
影响因子：
6.4
通讯作者：
Gupta, R. K.
中科院分区：
文献类型：
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作者：
Gregson, J.;Rhee, S. Y.;Gupta, R. K.
背景。M184V/I导致拉米夫定（3TC）和恩曲他滨（FTC）高度耐药以及富马酸替诺福韦二吡呋酯（TDF）敏感性增加。然而，3TC和FTC（统称为XTC）似乎对携带这些突变的人类免疫缺陷病毒 - 1仍保留一定活性，可能是由于复制能力降低。在本研究中，我们确定了M184V/I如何影响在含TDF/XTC加非核苷类逆转录酶抑制剂（NNRTI）方案治疗失败的患者中的病毒载量（VL）。
方法。我们使用随机效应荟萃分析在不同研究中比较了有和无M184V/I情况下的VL。在体外分析了突变对病毒逆转录酶活性和传染性的影响。
结果。在1445例病毒学失败（VF）个体中，817例（56.5%）存在M184I/V。有和无M184I/V的个体病毒载量相似（log(10) VL差值为0.18；95%置信区间为0.05 - 0.31）。在开始抗逆转录病毒治疗时以及在发生病毒学失败时，后来出现M184V/I的参与者的CD4计数均较低。在有M184V/I的人群中，10.2%存在L74I，而在无M184V/I的人群中不存在（P < 0.0001）。在体外，L74I补偿了M184V突变病毒的复制缺陷。
结论。在含TDF/XTC/NNRTI方案治疗病毒学失败期间，有和无M184V/I的个体病毒载量相似。因此，我们未发现在此联合用药一线治疗失败的情况下XTC有益的证据。
Background. M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen.Methods. We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro.Results. M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log(10) VL, 0.18; 95% confidence interval, .05-.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus.Conclusions. Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.