title: HIV-1 non-B subtypes: High transmitted NNRTI-resistance in Spain and impaired genotypic resistance interpretation due to variability.
abstract: Genotypic resistance algorithms interpret drug-resistance mutations, but are mainly developed for HIV-1 subtype B, meanwhile non-B subtypes cause 90% of worldwide infections. They include clade-specific amino acid at drug-resistance positions different than subtype B. This study explores: (i) the variability at resistance-related positions in 128 non-B and 226 B sequences from 354 treatment-naïve patients diagnosed in Spain (1999-2007); (ii) the discordances between five resistance interpretation algorithms (ANRS, Stanford, Rega, Geno2pheno, RIS); and (iii) the reliability of five subtyping tools (Stanford, Geno2pheno, Rega, NCBI, EuResist) for each HIV-1 variant. Primary drug-resistance prevalence was 13.6%, although higher in non-B vs. B subtypes (18.7% vs. 10.6%), due to a twofold higher NNRTI-resistance prevalence (15.7% vs. 7.6%). Most secondary PI-resistances, more frequent in non-B, were in fact clade-specific residues. Most sequences were interpreted as susceptible to all antiretrovirals by the five resistance algorithms, except for tipranavir by ANRS in non-B clades. Interalgorithm discordances were significantly higher in non-B variants for specific drugs. The agreement with phylogenetic analysis differed among subtyping tools testing non-B variants. We found a higher prevalence of NNRTI-resistance mutations in non-B subtypes. Certain algorithms overestimate the resistance in non-B subtypes due to natural patterns of mutations. Subtyping tools should be optimised for non-B variants.
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, Department of Microbiology, Hospital Universitario Ramón y Cajal and CIBER-ESP, Crta. Colmenar Viejo, Km. 9.100, Madrid 28034, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Yebra
authors.forename: M
authors.initials: M
authors.lastname: de Mulder
authors.forename: J
authors.initials: J
authors.lastname: del Romero
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: Holguín
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D015995:Prevalence; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D019380:Anti-HIV Agents