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Viruses 2016, 8(2), 48; doi:10.3390/v8020048

Genetic Variability of HIV-1 for Drug Resistance Assay Development

1
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, L-134, Stanford, CA 94035, USA
2
HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Ramón y Cajal-IRYCIS and CIBER-ESP, Madrid 28034, Spain
*
Author to whom correspondence should be addressed.
Received: 21 November 2015 / Revised: 2 February 2016 / Accepted: 3 February 2016 / Published: 11 February 2016
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

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. View Full-Text
Keywords: HIV-1; drug resistance mutation; variability; point-of-care HIV-1; drug resistance mutation; variability; point-of-care
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Clutter, D.S.; Sánchez, P.R.; Rhee, S.-Y.; Shafer, R.W. Genetic Variability of HIV-1 for Drug Resistance Assay Development. Viruses 2016, 8, 48.

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