Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy
Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy
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DOI：
10.1097/qad.0b013e32835b0f59
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发表时间：
2013-02-20
期刊：
影响因子：
3.8
通讯作者：
Blattner, William A.
中科院分区：
文献类型：
--
作者：
Etiebet, Mary-Ann A.;Shepherd, James;Blattner, William A.
背景：在资源有限的情况下，艾滋病毒-1耐药性检测，以指导抗逆转录病毒治疗（ART）的选择是不可用的。我们回顾性地进行了基因型分析存档样本尼日利亚患者接受有针对性的病毒载量检测，以确认治疗失败，并报告其耐药突变patterns.Methods：存储血浆从349名成人患者的非核苷类逆转录酶抑制剂（NNRTI）方案进行了测定HIV-1 RNA病毒载量，并与超过1000拷贝/ml的样本进行测序的pol基因。结果：175例标本进行基因分型，以G亚型（42.9%）和CRF02_AG亚型（33.7%）为主。患者接受抗逆转录病毒治疗的中位时间为27个月。90%有M184 V/I突变，62%有至少一个胸苷类似物突变，14%有K65 R突变。97%的患者有一个NNRTI耐药突变，47%的患者有至少两个依曲韦林相关突变。在多变量分析中，在调整亚型、既往ART、CD 4和HIV病毒载量后，替诺福韦为基础的方案不太可能有至少3个核苷逆转录酶抑制剂（NRTI）突变[ P < 0.001，比值比（OR）0.04]。70%接受基于替诺福韦的方案的患者至少有两种易感NRTI可纳入二线方案，而接受基于齐多夫定的方案的患者这一比例为40%（P = 0.04，OR = 3.4）。结论：在认识到治疗失败后，接受基于替诺福韦的一线方案的患者NRTI耐药突变较少，二线方案可用的NRTI药物更多。这些发现可以为ART方案排序策略提供信息，以优化低资源环境中的长期HIV治疗结果。(C)2013威科健康垂直酒吧Lippincott威廉姆斯&威尔金斯艾滋病2013，27：553-561
Background: In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns.Methods: Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list.Results: One hundred and seventy-five samples were genotyped; the majority of the subtypes wereG (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [ P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4).Conclusions: At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27: 553-561