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Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India

机译:印度南部基于替诺福韦的一线HAART失败患者中的基因型HIV-1耐药性

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摘要

According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.
机译:根据2013年WHO指南,替诺福韦(TDF)是成人和青少年的首选一线治疗方案。共有167名HIV-1感染的患者在基于TDF的一线HAART治疗后发生了免疫学衰竭,对他们的HIV-1 pol基因的RT区域进行了测序,IAS-USA 2014清单和斯坦福大学的HIV耐药性数据库用于突变解释。 REGA V3.0用于HIV分型。观察到的主要NRTI和NNRTI突变是M184IV(59.9%),K65R(28.1%)和胸苷类似物突变(TAMs,29.3%)和K103NS(54.5%),V106AM(39.5%)和Y181CIV(19.8%),分别。突变关联显示,K65R与TAM负相关(OR 0.31,p .008),M184V(OR 0.14,p .57)和K70E(OR 0.29,p .02)。基于突变模式的基因型预测耐药性水平显示,可以选择88%的叠氮胸苷(AZT),仍然可以选择65%的TDF。考虑到K65R突变在增加对AZT的易感性和其低患病率方面的性质,我们得出结论,在大多数基于TDF的一线治疗失败的患者中,可以考虑将AZT用于二线治疗,然后再考虑TDF本身。

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