Genetic Variability of HIV-1 for Drug Resistance Assay Development

被引：13

作者：

Clutter, Dana S. ^{[1
]}

Rojas Sanchez, Patricia ^{[2
,3
]}

Rhee, Soo-Yon ^{[1
]}

Shafer, Robert W. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, 300 Pasteur Dr,L-134, Stanford, CA 94035 USA

[2] Hosp Ramon y Cajal IRYCIS, Dept Microbiol & Parasitol, HIV Mol Epidemiol Lab 1, Madrid 28034, Spain

[3] CIBER ESP, Madrid 28034, Spain

来源：

VIRUSES-BASEL | 2016年 / 8卷 / 02期

关键词：

HIV-1; drug resistance mutation; variability; point-of-care; REVERSE-TRANSCRIPTASE; CROSS-RESISTANCE; SUBTYPE C; MUTATIONS; PROTEASE; IMPACT;

D O I：

10.3390/v8020048

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：10