Dinesha Thongadi Ramesh, Gomathi Selvamurthi, Boobalan Jayaseelan, Sivamalar Sathasivam, Solomon Sunil S, Pradeep Ambrose, Poongulali Selvamuthu, Solomon Suniti, Balakrishnan Pachamuthu, Saravanan Shanmugam
1 Y.R. Gaitonde Centre for AIDS Research and Education, Voluntary Health Services , Taramani, Chennai, India .
2 Johns Hopkins University School of Medicine , Baltimore, Maryland.
AIDS Res Hum Retroviruses. 2016 Dec;32(12):1234-1236. doi: 10.1089/AID.2016.0110. Epub 2016 Jul 14.
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.
根据世界卫生组织2013年的指南,替诺福韦(TDF)是成人和青少年首选的一线治疗方案。本研究纳入了167例接受基于TDF的一线高效抗逆转录病毒治疗(HAART)后出现免疫失败的HIV-1感染患者,对他们的HIV-1 pol基因RT区域进行测序,使用美国国际抗病毒学会(IAS-USA)2014年列表和斯坦福HIV耐药数据库进行突变解读。使用REGA V3.0进行HIV亚型分析。观察到的主要核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)突变分别为M184IV(59.9%)、K65R(28.1%)和胸苷类似物突变(TAMs,29.3%)以及K103NS(54.5%)、V106AM(39.5%)和Y181CIV(19.8%)。突变关联显示,K65R与TAMs呈负相关(比值比[OR]为0.31,p = 0.008)、M184V(OR为0.14,p = 0.57)和K70E(OR为0.29,p = 0.02)。基于突变模式的基因型预测耐药水平显示,88%的患者可选用叠氮胸苷(AZT),仍有65%的患者可选用TDF。考虑到K65R突变增加对AZT敏感性的性质及其低发生率,我们得出结论,在大多数接受基于TDF的一线治疗失败的患者中,二线治疗可考虑使用AZT,随后再使用TDF本身。