title: Genetic Variability of HIV-1 for Drug Resistance Assay Development.
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.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, L-134, Stanford, CA 94035, USA. dclutter@stanford.edu.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Clutter
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Ramón y Cajal-IRYCIS and CIBER-ESP, Madrid 28034, Spain. patriciarrojas@gmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rojas Sánchez
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, L-134, Stanford, CA 94035, USA. syrhee@stanford.edu.
authors.forename: Soo-Yon
authors.initials: SY
authors.lastname: Rhee
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, L-134, Stanford, CA 94035, USA. rshafer@stanford.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase
keywords: HIV-1; drug resistance mutation; point-of-care; variability