Clutter Dana S, Rojas Sánchez Patricia, Rhee Soo-Yon, Shafer Robert W
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, L-134, Stanford, CA 94035, USA.
HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Ramón y Cajal-IRYCIS and CIBER-ESP, Madrid 28034, Spain.
Viruses. 2016 Feb 11;8(2):48. doi: 10.3390/v8020048.
A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 reverse transcriptase (RT) sequences from the Stanford HIV Drug Resistance Database originating from six LMIC regions. We characterized the variability in a 27-nucleotide window surrounding six clinically important drug resistance mutations (DRMs) at positions 65, 103, 106, 181, 184, and 190. The number of distinct codons at each DRM position ranged from four at position 184 to 11 at position 190. Depending on the mutation, between 11 and 15 of the 24 flanking nucleotide positions were variable. Nonetheless, most flanking sequences differed from a core set of 10 flanking sequences by just one or two nucleotides. Flanking sequence variability was also lower in each LMIC region compared with overall variability in all regions. We also describe an online program that we developed to perform similar analyses for mutations at any position in RT, protease, or integrase.
一种基于杂交的HIV-1耐药性即时检测方法，对于那些无法常规进行耐药性检测的低收入和中等收入国家（LMICs）将非常有用。开发这种检测方法的主要障碍是HIV-1的极端基因变异性。我们分析了来自斯坦福HIV耐药数据库的27203条逆转录酶（RT）序列，这些序列源自六个LMIC地区。我们对围绕65、103、106、181、184和190位六个临床上重要的耐药性突变（DRMs）的27个核苷酸窗口内的变异性进行了表征。每个DRM位置的不同密码子数量从184位的4个到190位的11个不等。根据突变情况，24个侧翼核苷酸位置中有11到15个是可变的。尽管如此，大多数侧翼序列与一组10个核心侧翼序列仅相差一两个核苷酸。与所有地区的总体变异性相比，每个LMIC地区的侧翼序列变异性也较低。我们还描述了一个我们开发的在线程序，用于对RT、蛋白酶或整合酶中任何位置的突变进行类似分析。
